Excitable cells Flashcards
What do dorsal and ventral mean
Back & belly
what do cranial and caudal mean
head end & tail end
what do proximal and distal mean
close to and far away
what do anterior and posterior mean
front and back end
what is rostral interchangeable with
it is interchangeable with anterior and cranial in quadrupeds
what do medial and lateral mean
towards the midline & away from it
What are the two main subdivisions of the nervous system
central nervous system (CNS)
& peripheral nervous system (PNS)
What are motor/efferent neurons/nerves used for.
They carry signals TOWARDS the target tissue or organ
what are sensory/afferent neurons/nerves used for
detect change in the environment and carry signal about change to CNS
What are the two main structures in the CNS
Brain and spinal cord
what are the 4 main subdivisions of the CNS (this is including the divisions of the brain)
Forebrain, midbrain, hindbrain and spinal cord
What are the two main divisions of the PNS
sensory (afferent) division and motor (efferent division)
What type of nerves make up the Peripheral nervous system
cranial nerves & spinal nerves
What are the two division of the motor division of the PNS
Autonomic nervous system & Somatic nervous system
What are the two division of the motor division of the PNS
Autonomic nervous system & Somatic nervous system
Which of the two motor nervous systems is responsible for VOLUNTARY control
Somatic
which of the two nervous systems is responsible for INVOLUNTARY control
autonomic
what are the two subdivisions of the autonomic nervous system
Sympathetic and parasympathetic
What is the function of the sympathetic division of the ANS
mobilises body systems during activity
(Fight or flight response)
what is the function of the parasympathetic division of the ANS
Housekeeping functions & energy conservation
What brain divisions are common to all vertabrates
olfactory bulb, cerebral hemispheres, cerebellum, optic, tectum, medulla oblongata
What is special about jellyfish and other primitive animals that dont move
they do not have a nervous system but have a nerve net
what is the nervous system of arthopods like
organised, have a nervous brain and ventral nerve cords
where are the telencephalon & diencephalon located
forebrain
what forms part of the brain stem and also contains the mesencephalon
midbrain
what contains the rhombencephalon
hindbrain
what does the brainstem consist of
the midbrain and hindbrain
what are the inital 3 layers of an embryo and what do they become
endoderm- linings of organs
mesoderm - bones and muscles
ectoderm - nervous system & skin
What is the notocord derived from and what is it important for
- derived from the mesoderm & important for signalling
What is Anencephaly
a condition in which the neural tube closes,the anterior pore does not seal and the brain doesnt develop - fatal
What is spina bifida
it is resultant of failure for the posterior neural tube to close.
It typically results in paralysis
How many ventricles does the brain have and where are they?
- There are two lateral ventricles located at the top. The third ventricle is located in the centre and the 4th is located at the bottom, near the brainstem
What is the function of the brains ventricles
They contain CSF and act to provide nutrients, remove waste and cushion and support the brain
How do you decrease neural tube defects at birth?
by supplementing diet with folic acid in early pregnancy
what increases the risk of spina bifida
anti epilepsy/bipolar drugs interfere with folate metabolism
how many swellings are there at the rostral end of the neural tube when an embryo is 3-4 weeks old
there are 3 swellings and they become the primary Vesicles within the brain (forebrain,midbrain & hindbrain )
what is the oldest part of the brain
brainstem
what is the oldest part of the brain
brainstem
which part of the brain is the decision matrix
brainstem
What is hydrocephalus and how can it occur
an excess of CSF in the brainstem and can occur due to an injury to another part of the brain
what does the diencephalon contain
it contains the thalamus (used in sleep, & concious movement) and the hypothalamus (used in homeostasis and reproduction)
What is cerebella agnesis
complete absence of the cerebellum. Non-fatal, can result in mild cognitive impairment & medium motor problems
What is the neocortex
a highly developed 6-layer structure of the cortex that mammals have, the number of neurons is related to intelligence
why does cortical folding occur
to increase processing power/intellignece as it increases the number of cortical neurons
what is a dip in the cortex fold called
sulcus
what is a peak in the cortex fold called
gyrus
what is the frontal lobe used for
actions, motor control, speech control and emotion
what is the parietal lobe used for
sensory & language functions
how does sensory info enter the spinal chord
via dorsal roots (afferent neurons)
what do the ventral roots of the spinal cord contain
motor info (efferent neurons)
What is grey matter and what kind of structure does it have
neural cell bodies
butterfly structure
what is white matter
myelinated axons
what is the function of the occipital lobe
visual processing
what is the function of the temporal lobe
memory as well as sensory and language based info
Where is the somatomotor cortex( aka the primary motor cortex)
in the frontal lobe
which lobe is the somatosensory cortex located in
parietal lobe
What does decussation (to become crossed) mean in a neurological sense
we see contralateral motor and sensory pathways : the right side of the brain controls and receives sensory signals from the left side of the body and vice versa
What did golgi invent and how did this help him
invented silver staining, allowed to see structure of typical neuron due to staining
Which two principles did Cajal develop
Principle of dynamic polarisation
Principle of connectional specificity
what is the principle of dynamic polarisation
- neurons have preferred transmittance directions
what is the principle of connectional specificity
neurons do not make random connections, they contact other neurons and only the specified structures on them
what is the resolution of the human eye
0.1mm
what is the resolution of a Light microscope
0.1μm
what is the resolution of a Electron microscope
0.1nm
What is a disadvantage of using an electron microscope
the cells have to be fixed (dead)
what is florescence
- a property in which if a substance has light of particular wavelength shone on it, it emits light of a different wavelength
how is immunoflourescence labelling done
Prepare selective antibody tagged with fluorescent label
Add to tissue and allow to bind strongly
Wash off any free labelled antibody
Look for where the fluorescence is
Image distribution of fluorescence (corresponds to target proteins distribution)
what is often tagged with flourophores to locate specific cell components
antibodies
what is a limitation of flourescence staining
you need to have antibodies against proteins that only occur in neurons or whatever you’re comparing them to
what is confocal microscopy
-focusing a laser at diff levels in a piece of tissue thats been labelled with a fluorescent probe, and look to see where the fluoresces is coming from,
Which organisms have dorsal nerve cords?
vertebrates
What are glia
the supporting cells of the nervous system
in which region of the brain do glia outnumber neurons 17:1
thalamus
what is the primary role of glia
support the neurons
Which types of glia are found in the CNS
astrocytes, microglia, oligodendocytes, ependmyial cells
which type of glia is the most abundant
astrocytes
what is the function of astrocytes
regulate composition of extracellular fluid, important in proliferation & differentiation of neural stem cells
what do oligodendrocytes and schwann cells do
myelinate axons of neurons (oligo’s do it to many axons and schwann cells do it to a single axon)
what types of glia are found in the PNS
satellite cells and schwann cells
What kind of genetic disease is Huntington’s disease and what gene defect causes it
autosomal dominant disorder & caused by abnormallity in huntingtin gene
what is brainbow
:Genetically modifying an animal so that its cell produce random combos of up to 4 fluorescent dyes so cells will randomly be one of 100 diff colours.
what two types of protein deposits characterise alzheimers
Amyloid beta plaques and tau clumps (which form neurofibrillarly tangles)
List and briefly describe the three main components of the neuronal cytoskeleton.
Microtubules. Polymers of tubulin, 20 nm wide. Role: structure and support. Neurofilaments: 10 nm wide: mechanical strength. Microfilaments: actin polymers 5 nm. Tethered to membrane, mediate shape changes.
what is cerebella ataxias
aberrant movement coordination
what do ions have around them in solution
a hydration shell
what is the effective size of an ion based on
the hydration shell around the ion
what is the size of the hydration shell dependent on
charge density , smaller the ion, higher the charge density so larger the shell
what are some physiologically useful ions
Na+
K+
Cl-
what are some biochemically useful ions
Mg2+ and trace metals e.g Fe3+ & Zn2+)
is Ca2+ biochemically or physiologically important
it is both
what is the primary hydration shell
- the layer of water molecules that immediately contact the ion
do smaller or larger ions of the same size have greater mobility
larger ions do, they have a smaller hydration shell so have a smaller ‘effective’ size
what action do pumps perform
primary active transport
what is antiporting
the exchange of ions in an opposite direction
what is symporting
an ion aiding in transport of another ion in the same direction
give an example of one symporter and one antiporter
symporter- SGLT (Sodium-glucose linked transporter)
Anti-porter- sodium calcium exchanger
what is electrophoresis / electrophoretic movements
ion movement under the influence of an electric field
what is the total gradient equal to
the electrochemical gradient
what is OHMS law (as a word equation)
Current (I) = Volts (V)/ Resistance(R)
Current(I) = Volts (V) x Conductance (1/R)
what does ohms law state
the direction ions move in is determined by the electrochemical gradient
what influences the movement of ions
size of electrochemical gradient
nature of ion
number of open channels
properties of ion channels
what is selectivity in regards to ion channels
only taking specific ions
what is selectivity in regards to ion channels
only taking specific ions
what is permeability in regards to ion channels
degree to which ions are allowed to flow through
what is the conc of Sodium ions in & out of the cell (mM) & what is the ratio
150 outside, 15 inside (10:1 ratio)
what is the conc of potassium ions in & out of the cell (mM) & what is the ratio
5 outside, 100 inside (1:20 ratio)
what is the conc of calcium ions in & out of the cell (mM) & what is the ratio
2 outside, 0.0002 inside (10000:1)
what is the conc of chloride ions in & out of the cell (mM) & what is the ratio
150 outside, 13 inside (11.5:1 ratio)
sodium and calcium both diffuse ____ the cell as both of their conc gradients favour this movement
in to
Potassium and chlorine both have _________ concentration and chemical gradients so it is _________ their movement
opposing
hard to predict
if total work > 0 then ?
energy is needed to move ions across the membrane
if total work < 0 then ?
energy is released when ions move across the membrane
when the nernst equation is in equilibirum, there is no net movement , why?
The electrical gradient exactly balances out the chemical gradient
why is resting membrane potential not the same as EK (equilibirium potential)
Sodium ions can also cross the membrane and this has consequences for Ek , RMP is more positive than equilibrium potential
Because PK (permeability to potassium) is 40x greater than PNa (permeability to sodium, what does this mean for the relationship of of Resting membrane potential and EK
RMP is much closer to EK (equilibirum potential for potassium) than ENa (equilibrium potential for sodium)
what is the GHK (Goldmann-Hodgin-Katz) equation and why is it used
it is a weighted form of the nernst equation and it allows us to calculate resting membrane potential
What is the reason that the resting membrane potential of neurons is close to the equilibrium potential of potassium (EK)?
The resting membrane potential of neurons is close to EK because the membrane is more permeable to potassium ions than any other ion at rest.
What is the primary ion responsible for establishing the resting membrane potential in neurons?
Potassium ions are the primary ion responsible for establishing the resting membrane potential in neurons.
What is the first ion current to activate during an action potential?
The first ion current to activate during an action potential is the inward sodium current (Na).
What ion current is responsible for repolarization of the neuron during an action potential?
The outward potassium current (K) is responsible for repolarization of the neuron during an action potential.
What is the ion current responsible for the hyperpolarizing afterpotential seen after an action potential?
The activation of the potassium current .
you just need to know that its a potassium current
: What is the mechanism by which voltage-gated ion channels open and close?
in the voltage across the membrane, which cause conformational changes in the channel protein.
: What is the mechanism by which voltage-gated ion channels open and close?
in response to changes in the voltage across the membrane, which cause conformational changes in the channel protein.
What is the significance of the selectivity filter in voltage-gated ion channels?
ensures that only ions with the appropriate charge and size can pass through the channel pore.
what kind of structure do voltage gated potassium channels have
tetramers, crystal structure, composed of 4 individual subunits
What is the mechanism of inactivation in voltage-gated sodium channels?
cytoplasmic segment of the channel protein blocks the channel pore.
What is the importance of inactivation in voltage-gated sodium channels for the action potential?
ensures that the sodium current is not forever continuous,
helps contribute to the rising and falling phases of the action potential.
What is the difference between fast and slow inactivation in voltage-gated sodium channels?
Fast = occurs rapidly after the channel opens, slow =over a longer period of time, results in a decrease in channel conductance.
What is the absolute refractory period?
period after a fired action potential in which the neuron requires a greater stimulus to create another (the dip)
What is the relative refractory period?
period during which the neuron can generate another action potential, but only in response to a stronger-than-normal stimulus.
How does the refractory period allow action potentials to spread directionally?
preventing the action potential from re-activating in the region of membrane that has just undergone an action potential. ensures that the action potential can only propagate in one direction, from the initial site of depolarization to the axon terminals
What type of genetic mutation is associated with Dravet Syndrome?
mutations in the SCN1A gene, which encodes the voltage-gated sodium channel **Nav1.1.
What are some examples of epilepsies that have been shown to respond to treatment with cannabinoids?
Dravet Syndrome, and some forms of focal epilepsy.
what changes in ion currents cause the refractory period to occur
due to inactivation of Na current and activation of K current
is transmission within dendrites active or passive
passive
is current attenuated in dendrites or axons
dendrites (due to current leaking out of the cell membrane)
what is length constant dependent on
Rm (inversly proportional to leakiness)
Ri( resistance, want as low as possible)
And diameter
how can the efficiency of transmission through cables be increased
increasing insulation (increases Rm)
having better conductance cores (decreases Ri)
having cables with larger diameters
What are some of the key electrical properties of cables?
Resistance, capacitance, and inductance.
How do axons transmit signals?
through the generation and propagation of action potentials.
What is the length constant?
the distance where the voltage drops to 37% of its original value.
What factors determine the length constant?
Rm (inversely proportional to leakiness), Ri (resistance, we want as low as possible, lower resistance, higher conductivity) and diameter (want large).
How do unmyelinated neurons transmit signals?
via a wave of action potentials that travel along the length of the axon.
How do unmyelinated neurons transmit signals?
via a wave of action potentials that travel along the length of the axon.
How do myelinated neurons transmit signals?
via saltatory conduction, - rapid propagation of action potentials along the myelinated segments of the axon and passive transmission across the non-myelinated segments.
what is density of sodium channels of axons compared to dendrites
(100-200 Na channels per μm/ 2 per μm)
what is special about the axon hillock
v high density of sodium channels
thought to be where action potential started off in the axons
how do we tend to get a bigger length constant in nature
(higher Rm & a larger diameter, NOT better conducting cores)
what is special about the squids giant axon and why is this not suitable for other animals
Increased axonal diameter
no good for animals w/ complex nervous systems - fat heads
Myelination
How does myelination improve the conduction velocity of neurons?
reducing the capacitance and resistance of the axon membrane,
decreases the leak of current and increases the thickness of the insulation around the axon.
What is the relationship between axon diameter and conduction velocity?
Conduction velocity increases with axon diameter.
What is multiple sclerosis?
chronic autoimmune disorder characterised by demyelination of CNS neurons caused by an immune attack on oligodendrocytes that provide myelin sheath
what is the density of sodium channels at internodes
20/μM
what is the density of sodium channels at nodes of ranvier
estimated 1200 sodium channels /μM,
what is saltatory conduction
a wave of action potentials interspersed by segments of rapid cable conduction
How is MS diagnosed?
MRI scanning
Visual evoked potential (VEP) test
What are some treatments for MS?
disease-modifying therapies (DMTs),
Some DMTs are injectable, while others are oral or infused.
What are the pathological mechanisms of multiple sclerosis?
Caused by an immune attack on oligodendrocytes that provide myelin sheath insulation that facilitates saltatory conduction
which neuron fibres have a large diameter(13-20micrometres) and are myelinated whilst conducting fast transmission
A-alpha fibres
Which neuron fibre has a medium diameter (6-12micrometres), is myelinated and conducts intermediate speed transmission
A-Beta fibres
which neuron fibre has a small diameter (1-5 micrometres), a very thin myelin sheath and conducts slow transmission
A-delta fibres
which neuron fibre has a Very small diameter(0.2-1.5 micrometres), NO myelin sheath and conducts very slow conduction
C fibres
What auto-immune disorder is characterised by schwann cells being attacked & the peripheral nervous system neurons becoming demyelinated
Guillain-Barre Syndrome
What is the difficulty in action potentials jumping between neurons?
Action potentials cannot easily jump between neurons due to the synaptic gap.
Is there a direct transmission of action potentials between neurons?
No, action potentials are not directly transmitted between neurons.
what is a gap junction
a structural feature of electrical synapses formed by proteins in the membranes of two neurons docking to each other. It is a 3.5 nanonmetre gap
what are the proteins that form gap junctions called and what are their subunits called
Connexons, made up of 6 connexins
relative to an ion channel, what is the structure of connexons like
bigger than ion channels, big enough for both ions and small molecules (things up to 1000 molecular weight) to be transported between 2 neurons
What do electrical synapses provide between neurons?
Electrical synapses provide a continuous cytoplasmic connection between neurons.
Are electrical synapses fast or slow?
Electrical synapses are fast.
How are neurons connected in electrical synapses?
Neurons are connected by gap junctions in electrical synapses, allowing direct ion flow between them.
are electrical synapses common or uncommon in vertebrate nervous systems
uncommon, used in systems where you need an escape reflex
what is a limitation of gap junctions and electrical synapses
need specialised situations, not very flexible & don’t have as much plasticity as chemical synapses
drosophilia flies have an escape system using electrical synapses
What are the gap junctions in drosophilia flies formed by and what happens to these in the mutant version
Innexins, in the mutant flies, these become disrupted meaning the escape reflex is disabled
What is the main form of communication in a chemical synapse?
through the release of chemical neurotransmitters.
How is the electrical signal transformed in chemical synapses
transformed into chemical signals, which bathe the second neuron and excite an electrical signal in the second neuron.
What is Synaptic Dysfunction
abnormalities or impairments in the communication between neurons at synapses, leading to disruptions in normal neural signalling.
What is Long-Term Potentiation (LTP)
process by which synaptic strength is enhanced, resulting in an increased efficiency of neural communication.
What does excitotoxicity mean?
pathological process in which excessive stimulation of neurons, particularly through the activation of glutamate receptors, leads to cellular damage and neuronal death.
What does channelopathy mean?
(CHANNEL-opathy)
term used to describe a group of disorders that arise from dysfunctional ion channels in cells.
What does synaptopathy mean?
Synaptopathy refers to disorders or conditions characterized by impaired synaptic function.
Outline what astrocytes are and their role.
Astrocytes are a type of glial cell in the central nervous system (CNS) that play diverse roles in supporting neuronal function.
What can cause synaptic dysfunction?
It can result from various factors, such as alterations in neurotransmitter release, impaired receptor function, or structural changes in synapses.
What is LTP a mechanism for?
It is considered a cellular mechanism underlying learning and memory formation. LTP involves the strengthening of existing synapses or the formation of new synapses.
Outline how excitotoxicity can occur.
It can occur in various neurodegenerative diseases and stroke, where excessive glutamate release overwhelms the ability of neurons to maintain ion homeostasis.
What can channelopathies lead to?
abnormalities in the electrical signalling of neurons, muscles, or other tissues, resulting in various clinical manifestations.
Examples include cystic fibrosis, long QT syndrome, and epilepsy
What is the primary way neurons communicate in animal nervous systems?
Neurotransmission (chemical signaling) is the primary way neurons communicate, providing high flexibility and plasticity.
What are some ways in which synaptopathies can be expressed biologically?
abnormalities in neurotransmitter release, synaptic connectivity, or synaptic signalling
Leads to disrupted neural communication.
Who discovered the first neurotransmitter and what was it?
Otto Loewi discovered the first neurotransmitter, which is acetylcholine.
What are some examples of synaptopathies?
autism spectrum disorders, schizophrenia, and Alzheimer’s disease.
What can happen to astrocytes during disease?
undergo reactive gliosis - become hypertrophic, proliferate, and release various inflammatory molecules.
can contribute to neuroinflammation and tissue damage.
what does stimulating the heart via the vagus nerve do?
slows it down
What are microglia and what is their role?
resident immune cells of the CNS and act as the primary mediators of immune responses in the brain.
What can happen to microglia in disease?
can undergo morphological changes, transitioning from a resting state to an amoeboid/phagocytic state.
Become activated & release pro-inflammatory cytokines and can contribute to neuroinflammation.
What can happen to oligodendrocytes in disease?
can be damaged or destroyed, leading to demyelination.
How are natural toxins used in studying synaptic function
by selectively affecting specific components of the synaptic process.
What is neuroinflammation?
inflammation that occurs in the central nervous system (CNS) as a response to injury, infection, or disease.
What does neuroinflammation involve (which cells and what effects can it have on the CNS)?
microglia and astrocytes release inflammatory mediators,
recruitment of immune cells to the affected area
Neuroinflammation can have both protective and detrimental effects on the CNS.
Which diseases are caused by natural toxins that affect synaptic function?
Tetanus/lockjaw and botulism
What can the study of natural toxins teach us about synaptic function?
provide insights into the mechanisms of synaptic transmission and help understand diseases related to synaptic dysfunction.
What is meant by inflammatory mediators?
substances released during neuroinflammation that contribute to the immune response in the CNS.
What is the role of calcium in neurotransmitter release?
Neurotransmitter release is Ca2+-dependent, meaning calcium ions trigger the release of neurotransmitter vesicles.
What does the vesicle hypothesis propose about neurotransmitter release?
neurotransmitter release occurs in discrete packets called quanta or vesicles.
Give some examples of inflammatory mediators. (What can they influence?)
cytokines, chemokines, prostaglandins, and reactive oxygen species.
can influence neuronal function, modulate immune responses, and promote tissue repair or damage.
What is the blood-brain barrier (BBB)?
specialized barrier formed by tight junctions between endothelial cells in brain capillaries.
What can happen to the blood-brain barrier during neuroinflammation?
the integrity can be compromised, allowing immune cells and inflammatory mediators to enter the brain more easily.
BBB dysfunction = associated with pathogenesis of several neurological disorders.
What is the role of the blood-brain barrier?
regulates the exchange of substances between the bloodstream and the brain,
formed by endothelial cells, tight junctions, and specialized transport systems.
How is neurotransmitter release quantal?
it occurs in specific and measurable amounts, corresponding to the release of individual synaptic vesicles.
Outline the relationship between drug delivery and blood-brain barrier.
poses a challenge for delivering drugs to the brain.
tight junctions and efflux transporters limit the passage of many therapeutic agents.
What happens to synaptic vesicles after neurotransmitter release?
Synaptic vesicles are recycled after neurotransmitter release.
How are synaptic vesicles recycled?
Synaptic vesicles undergo endocytosis, where they are retrieved from the plasma membrane and reform inside the neuron.
Why is recycling of synaptic vesicles important?
allows for sustained neurotransmitter release and the replenishment of vesicles for future neuronal signaling.
Outline what can happen as a result of the break down of the blood-brain barrier.
it allows the infiltration of immune cells, inflammatory mediators, and potentially harmful substances into the brain, contributing to further tissue damage and neurological complications.
What is meant by excitable cells?
cells that can generate or propagate action potentials or electrical impulses
Outline the existence of excitable cells in organisms.
commonly associated with neurons and muscle cells,
also exist in plants, bacteria, and single-celled eukaryotes.
Give examples of excitable cells in plants.
guard cells in stomata, which regulate gas exchange,
Venus flytrap, which uses electrical signals to trigger its snapping mechanism.
What snare proteins are important in the release of vesicles
Synaptobrevin -present on the vesicles
SNAP25 -present on nerve terminal membrane
Syntaxin - present on nerve terminal membrane
Synaptotagmin- calcium sensing vesicle protein
what is an evoked release
involves the action potential activating the calcium channels, many vesicles are releasing their neurotransmitters at once, causing a large response . If dealing with muscle, this is called a full end plate potential
what is spontaneous release
release of the neurotransmitters that occurs when there is no action potential and thus no calcium entry
the response is much smaller and a smaller size of change in the membrane potential in the postsynaptic neuron, this is a miniature end plate potential
Give examples of excitable cells in bacteria.
Paramecium:
- Front end has mechanoreceptors linked to Ca2+ channels. (Activation causes ciliary to beat in reverse direction from stimulus - aka swim backwards)
- Back end has mechanoreceptors linked to K+ channels. (Activation leads to faster rate of swimming forwards)
does vesicular release require an action potential
no, spontaneous vesicular release does not require calcium entry or an AP
how is quantal content calculated
end plate potential (evoked release) / the size of 1 quantum current
Outline the evolutionary origins of ion channels.
Potassium channels are probably the earliest members of the family, then calcium channels followed by sodium channels.
Outline the structure of and how cilia move in paramecium.
They move in a wave/whip like co-ordinated fashion.
formed from a 9+2 arrangement (9 pairs outside, 2 in middle) of microtubules termed the axoneme which is stabilised by protein cross-links via the motor protein dynein.
Outline what effect a single gene mutation can have in paramecium
Deficits in locomotor responses.
What is the pawn mutation of paramecium?
Cannot reverse direction - show little or no calcium current (cannot generate action potentials)
What is the dancer variation of paramecium?
Shows an enhanced calcium current - They reverse direction in response to much weaker stimuli than normal cells.
What is the pantophobiac variation of paramecium?
Have reduced voltage gated potassium channel current and show prolonged depolarisation - this means that they swim backwards for much longer than the wild-type.
In laymans terms, they have a lower threshold in order to swim backwards thus swim backwards for longer
What are some evolutionary reasons for rapid movement to be present in plants?
Protection from damage (predation)
Prey capture (venus fly trap)
Spreading pollen and seeds
What does the presence of the ability to produce rapid movement in plants suggest about plants?
There is some kind of sensory system
Fast signal transmission system is present.
There is some kind of mechanism to produce movement.
What is the mimosa pudica? Outline why it is special.
The ‘sensitive plant’ - It is capable of rapid and co-ordinated movement of its leaves (will curl up in response to touch).
What action does the mimosa pudica produce in response touch?
It’s leaves will fold up to expose its thorny stems to predators
What is the mechanism behind mimosa pudicas response to touch?
It is called ‘excitation-turgor loss coupling’
Which is movement brought about a chloride ion-based action potential which leads to cell shrinkage.
What happens when neurotransmitters bind to receptors?
Neurotransmitters influence the conformation (shape) of the receptor they bind to.
How do neurotransmitters affect receptors?
Neurotransmitters induce conformational changes in receptors, leading to downstream signaling events.
Outline the mechanism of ‘excitation-turgor loss coupling’.
The stimulus of touch is applied.
When the action potential is fired, the rising phase is due to chloride efflux (negative ions leaving the cell)
Repolarisation occurs due to potassium efflux.
Therefore, there is a net loss of KCl from the cell and water follows out via osmosis - reducing the turgor of the cell.
What is the size relationship between receptors and ligands?
Ligands are much smaller than receptors, allowing them to bind to specific binding domains.
what superfamily do nictonic receptors fall into
cys-loop receptors
What two physiological changes can occur due to long-term potentiation?
Increased dendritic spine size
Increased number of dendritic spines
how many agonist sites do multisubunit transmembrane proteins have
at least two
What is epilepsy?
Characterised by the occurrence of epileptic seizures, which are uncontrolled and excessive synchronised electrical activity of central neurons.
What are the different mechanisms by which ligands can act on receptors?
Ligands can act as agonists, partial agonists, antagonists, or allosteric modulators.
What is the hypothesis of the cause of epilepsy?
It is thought to be caused by an imbalance of excitatory and inhibitory circuits:
- Glutamatergic neurotransmission is enhanced
- GABA release is decreased
This leads to an increase in excitatory neurotransmission.
How do antagonists work?
Antagonists block the activation of receptors by preventing neurotransmitter binding.
What are partial agonists?
only produce a partial response, meaning their activity is weaker compared to full agonists. They can both activate and block the receptor, depending on the existing level of receptor activation.
What pathology is Levetiracetam for and how does it work to treat said pathology?
Epilepsy:
It reduces the neurotransmitter release at glutamatergic synapses.
What are allosteric modulators?
bind to the allosteric site, instead of the active site where agonists typically bind. They can enhance or inhibit the receptor’s activity, often by modifying the receptor’s response to agonists or antagonists.
What pathology is Valproate for and how does it work to treat said pathology?
Epilepsy
It increases the amount of inhibitory GABA
What determines the postsynaptic action of a neurotransmitter?
The postsynaptic action of a neurotransmitter depends on the specific receptors it binds to.
Can the same neurotransmitter have different effects in different synapses?
Yes, the same neurotransmitter can have different effects depending on the receptors present in the postsynaptic membrane.
What pathology is Phenytoin for and how does it work to treat said pathology?
Epilepsy
It prolongs the inactivation of Na+ channels (inhibitory effect - decreases the amount of APs that can be transmitted)
How do different receptors influence the postsynaptic action of a neurotransmitter?
Different receptors can activate different signaling pathways, leading to diverse postsynaptic effects of the same neurotransmitter.
What type of channel plays a key role in controlling neuronal excitability?
Ion channels (ligand and voltage gated)
Are GCPRs metatropic or ionotropic and what is an example of one
metatropic
β2-adrenoceptor
What are repolarisation deffects?
Means that cells/neurons are in a depolarised state for longer than usual
what is the largest receptor family
GCPRs
How many transmembrane domains do GCPRs have
7
What is a mutation in the GRIN28 and what effect does it have?
It is a mutation in the gene encoding the NR2B, the beta-2 subunit of the NMDA receptor.
It can lead to hyperexcitability (GoF)
It can lead to hypoexcitability (LoF)
What is the NMDA receptor?
A ligand gated ion channel that binds to glutamate
what are the 3 main g proteins and what do they do
Gs stimulates
Gi - inhibits
Gq
Gs and Gi operate on adenylate cyclase -Adenylate cyclase converts ATP into AMP
Gq operates on IP3 pathway
are G proteins dimeric
no, they are trimeric
What is myotonia congenita?
The condition that causes ‘fainting’ in goats.
It’s caused by a mutation in the skeletal muscle chloride channel CLCN1 which causes the goats to have an inability to relax after they have contracted.
What do Receptor tyrosine Kinases do and what is an example of one
transmembrane proteins which bind peptide hormones, growth factors & cytokines,
they Phosphorylate target protein tyrosines
Example: insulin receptor
What is malignant hyperthermia?
Caused by a mutation in the ryanodine receptor (sarcoplasmic reticulum channel)
- It involves a state of hyperactivity in muscle cells due to excessive release of calcium from the sarcoplasmic reticulum.
- This causes muscles to contract and become rigid which causes a high fever and a very fast heart rate.
what is special about nuclear hormone receptors and what are some examples
Only receptor type that is intracellular
Effects tend to be slower than other receptor types
hours to days
Examples: oestrogen, progesterone & glucocorticoid
What can happen if malignant hyperthermia is untreated?
Causes rhabdomyolysis (muscle breakdown)
Very high blood potassium levels (potentially fatal)
what do NHRs do
Bind to lipid soluble ligands e.g. steroids
Increase/decrease transcription of specific genes
What are the roles of the astrocytes?
Structural
Metabolic sensing
Repair
Modulation of synapse transmission
What is astrodegeneration?
The atrophy and functional asthenia (lack of energy or strength) which is neurotoxic and decreases their abilities.
- Occurs in Alzheimer’s/Huntington’s
What are the three functional states of microglia?
Nurturer
Sentinel
Warrior
what are some examples of cys loop receptors
GABAa
5HT3 receptor
Inhibitory glycine receptor
nAChR
Outline the nurturer as a functional state of microglia
Synaptic remodelling and migration
Removal of apoptotic neurons
They are evenly spaced out
are Ionotropic glutamate receptors part of the cys-loop receptor super family
no, but function similarly
Outline the sentinel as a functional state of microglia
Surveillance and sensing
They have lots of processes and are in motion.
Outline the warrior as a functional state of microglia
Defence against infectious pathogens and injurious-self proteins.
They are stocky and accumulate.
what is the desensitisation mechanism of Ligand gated ion channels
close channel if ligand binds for too long
what is the ligand gated ion channel we understand best and how many subunits does it have
nAChR, 5 subunits
What are the three main classes of neurotransmitters and give examples of each
amino acids, - L glutamate, glycine & aminobutyric acid
(mono) amines,
anything ending in amine (dopamine, histamine), (nore)epinephrine, serotonin (ACh is an amine not a monoamine)
and peptides.
endorphins, vasopressin, oxytocin
what is dales principle and is it true
A neuron only releases one type of neurotransmitter (he never said this, but was the interpretation)
THIS IS NOT TRUE
What is the term for neurons that release multiple neurotransmitters?
Neurons that release multiple neurotransmitters are called co-transmitters.
Why is the ability to release multiple neurotransmitters important?
allows for complex and diverse signaling within the nervous system.
What are the two main types of neurotransmitter receptors?
The two main types of neurotransmitter receptors are ionotropic and metabotropic.
How do ionotropic receptors work?
Ionotropic receptors directly open ion channels upon neurotransmitter binding, leading to rapid synaptic transmission.
What is the mechanism of action for metabotropic receptors?
activate signaling pathways through G proteins, which ultimately lead to cellular responses.
Outline how Tau (dementia) and HTT (huntingtons) are associated with microglia and neurodegeneration.
In these diseases the respective proteins are produced.
This causes the microglia to change in response to the pathology (turn to warrior state) in attempts to clear the disease stimulus.
However, the stimuli inhibit it’s ability to do this which leads to exaggerated proinflammatory response.
Therefore neurotoxicity and neurodegeneration.
What is the most common pathology associated with oligodendrocytes?
Multiple sclerosis (demyelination of axons)
What is multiple sclerosis?
It is a pathology that occurs due to the demyelination of neurons and it characterised by:
- Limb numbness/weakness
- Vision problems
- Fatigue/dizziness
- Tremor
What is the main cause of neuroinflammation and what are two key examples?
Invading immune cells:
- Encephalitis
- Multiple sclerosis
In neurodegenerative processes - such as parkinsons and alzheimers, what is inflammation triggered by?
CNS-resident cells
Outline neuroinflammation and what it results in.
It is an inflammatory response in the central nervous system.
Immune cells cross the blood brain barrier and infiltrate nervous tissues - activating microglial cells.
this process induced modification in neuronal and synaptic environment which increases the concentration of pro-inflammatory cytokines and reactive oxygen species (ROS).
This can lead to significant damage to cell structures known as oxidative stress.
What is the blood brain barrier?
It is the continuous endothelial membrane of the brain vasculature.
It restricts the movement of solutes and the migration of cells and pathogens into the brain.
What are the layers of protection associated with endothelial cells in the BBB?
(From inside to out)
- endothelial cells (with tight junctions)
- pericyte
- basement membrane
- astroglial ‘foot’
What does delivery of drugs through the BBB require?
Healthy blood vessels
Adequate blood flow
Recruitment of active transport systems
what type of responses do nicotinic and muscarinic recepotrs give
nicotinic - Excitatory
Fast responses µs-ms
Muscarinic -
Excitatory or inhibitory dependant on subtype
Slow responses ms-s
Outline the BBB and delivery of drugs in relation to Parkinson’s.
In Parkinson’s, there is a lack of dopamine.
Dopamine cannot cross the BBB.
L-DOPA, a precursor to dopamine can cross the BBB via CMT (carrier mediated transport)
Therefore L-DOPA is used instead of dopamine as a treatment.
what are some examples of ionotropic ligand gated ion channels
AMPA ()
Kainate
NMDA
what are some characteristics of NMDA receptors
Highly permeable to Ca2+
Blocked by Mg2+ at RMP
Need glycine (or D-serine) as a co-agonist
4 subunits, need 2 glutamate and 2 glycine to bind to open
What can occur as a result of a breakdown of the BBB? (loads listed)
Increased vascular permeability
Toxic blood-derived molecules, cells and microbial agents enter the brain.
Inflammatory and immune responses.
Neuronal injury, synaptic dysfunction, loss of neurons, loss of brain connectivity
Neurodegeneration.
metabotropic glutamate receptors are members of family C GCPR, which means they always operate as ____
dimers
At which levels do rhythms/clocks play an important role?
Physiological
Cellular
Association with disease.
GABA A/C receptors are ____
Opposed to GABA B receptors which are ___
ionotropic (ligand gated ion channels) , metabotropic (family C GCPRs)
Outline some physiological rhythms.
○ Sleep/wake
○ Body temperature
○ Cardiac output
○ Memory
○ Energy metabolism
○ Eating behaviour
○ Immune response
Detoxification
Outline some cellular rhythms.
○ Cell cycle progression
○ DNA damage repair
○ Cellular energy metabolism
○ Cell detoxification
Neuronal excitability.
What is an autoreceptor and what is an example of one
Receptors for neurotransmitter released by the nerve terminal in the membrane they reside in, regulate the release of that neurotransmitter
Usually inhibitor (negative feedback)
Alpha type 2 adrenoceptors which regulate noradrenaline release from cardac sympathetic neurons
Outline diseases that are associated with biological rhythms.
○ Affective disorders (Bipolar, depression)
○ Sleep disorders
○ Neurodegenerative disease (Alzheimer’s)
○ Obesity/metabolic syndrome
Inflammation (Asthma, COPD)
Outline the relationship between physiological, cellular and diseases in relation to rhythms.
Cellular rhythms lead to physiological rhythms which will in turn impact diseases associated with rhythms
what are heteroreceptors and what is an example of one
Responds to a diff neurotransmitter than that released by the neuron its embedded in
presynaptic nAChR’s - acetylcholine regulates dopamine release in the striatum
What are some modern aspects of our lifestyle that oppose our natural rhythms?
Chronic shift work
Sleep deprivation
Altered eating habits
Jet lag
what does the striatum contain
a high conc of dopaminergic synapses
What are the 4 types of rhythms?
Ultradian
Circadian
Infradian
Circannual
How long are ultradian rhythms?
<20h
How long are circadian rhythms?
20-28h
How long are circadian rhythms?
20-28h
How long are infradian rhythms?
> 28 hours
What is Lynx 1 and what does it do
member of Ly6 superfamily, is a protein that interacts with nAChRs to change their protein (important in regulating regulatory systems)
How long are circannual rhythms?
Annual/seasonal
what are some examples of proteins that regulate regulatory systems
Alpha-bungarotoxin = a peptide toxin that targets the skeletal muscle nAChR
Alpha-neurotoxins - usually target nicotinic acetylcholine receptors
Alpha-conotoxins are a group of small peptide toxins from marine snails
Through which mechanisms can neurotransmitters and modulators act in synapses?
through various mechanisms, including receptor binding, modulation of ion channels, and second messenger systems.
Outline 4 key features of the mammalian circadian system.
It is a self-sustained oscillator
Has a period of ~24 hours
Entrained by the environment (mostly by light)
Rhythmical outputs are on a cellular to physiological level.
How are neurotransmitters removed from the synaptic cleft?
Mechanisms such as reuptake, enzymatic degradation, and diffusion help remove neurotransmitters from the synaptic cleft.
How are neurotransmitters removed from the synaptic cleft?
Mechanisms such as reuptake, enzymatic degradation, and diffusion help remove neurotransmitters from the synaptic cleft.
Give an example of enzymatic degradation of neurotransmitters.
Acetylcholine is degraded by the enzyme acetylcholinesterase in the synaptic cleft
Give an example of enzymatic degradation of neurotransmitters.
Acetylcholine is degraded by the enzyme acetylcholinesterase in the synaptic cleft
What is the SCN?
suprachiasmatic nucleus (regulates biological rhythms)
What is the main inhibitory neurotransmitter in the brain?
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the brain.
Where is the SCN located and what is its basic structure?
In the hypothalamus, a pair of nuclei next to each other with roughly 10,000 neurons each.
How do glutamate receptors function?
Glutamate receptors mediate excitatory neurotransmission in the brain and are important for synaptic plasticity and learning.
What is the RHT and what does it do?
It is the retinohypothalamic tract and it connects the hypothalamus to the retina
What are some mechanisms of short-term synaptic modification?
Short-term synaptic modification can occur through processes like synaptic potentiation or depression.
How can synaptic function be modified in the long term?
Long-term synaptic modification involves structural and functional changes in the synapse, including synaptic plasticity and long-term potentiation (LTP) or long-term depression (LTD).
Are postsynaptic potentials graded or all-or-nothing?
Postsynaptic potentials are graded, meaning their amplitude can vary depending on the strength of the input.
What is the axon hillock?
region of a neuron where the axon originates from the cell body.
How is neuronal output computed at the axon hillock?
Inputs from multiple synapses are summed at the axon hillock, and if the threshold is reached, an action potential is generated.
How is information encoded in the nervous system?
through the pattern and frequency of action potentials generated by neurons.
What is frequency modulation in relation to action potentials?
changes in the firing rate of action potentials to convey different aspects of information.
How does a frequency-modulated action potential code convey information?
Different frequencies of action potentials can represent different stimulus intensities or encode specific features of sensory input.
What does photic information travel through and where is it processed?
The retinohypothalamic tract (RHT) and it’s processed in the core SCN
Briefly outline the route and processing of photic information.
Travels via the RHT to the core SCN where it will process this information and adjust the circadian rhythms accordingly
Then passing information to the shell SCN.
The shell SCN will then send projections to other parts of the brain, that sends connections to the organs they’re associated with, causing the organism to be in synchronisation
what is temporal summation
Multiple PSP’s from a single synapse , how often do they occur
what is spatial summation
Post synaptic potentials (PSP) form multiple synapses effect summation of a neuron
How close/far to hillock/initial segment
what does cable theory suggest
Dendrites behave like cables
PSPs travel from dendrites to hillock/initial segment passively & attenuate
By the time we get to the hillock, we have severe attenuation
what is shunting inhibition
an inhibitory synpase being located closer to the axon hillock than an excitatory synapse, causing the inhibition of an excitatory response
what code the neurons use in order to encode information
frequency modulation - constant amplitude but changes frequency that the signal is sent
Outline the molecular clock.
Inside cells there is a molecular clock comprised of genes called clock genes.
These genes are expressed in a rhythmic fashion which ultimately generates circadian rhythms in neuronal function
Outline some functions that clock genes regulate.
Neuronal firing
Neuropeptide secretion
Behavioural state
Gene expression
What is the sleep hormone and what is it secreted by?
Melatonin is secreted by the pineal gland
When does melatonin secretion occur?
During sleep/pre-sleep when there is no/less light
Name the gland that the SCN is associated to.
Pineal gland.
Where is the circadian expression of clock genes found?
In almost every single cell in our body.
What is known as ‘the master pacemaker’ of all clocks in the body?
The SCN
What is chronopharmacology?
It is the study of the manner and extent to which the kinetics and dynamics of medication are affected by the endogenous biological rhythms.
and…
How the dosing time of medications affects biological timekeeping and features of biological rhythms.
What is the relationship between time of tolerability and the time of best efficacy? - what field is this related to?
They coincide and it is in relation to chronotherapy.
Outline oxaliplatin. (study too)
It is the first anticancer drug to undergo chronotherapeutic development.
A study found that when it was tested as a chronodrug as apposed to a constant rate drug:
- the mean dose of oxaliplatin and its maximum tolerated dose could be increased by 15% if given in a circadian rhythm-modulated rate.
Outline lithium in realtion to chronodrugs.
It is a first line treatment for bipolar disorder which causes period lengthening and phase delay of the sleep-wake and body temperature rhythm
List some mood disorders that bright light therapy can be used on - what are its benefits?
Seasonal affective disorders
Unipolar and bipolar depression
(and other forms of depression)
benefits:
- Improved mood
- Enhanced sleep efficiency
Why is sleep necessary?
It is a basic homeostatic need which is important for learning, memory, growth and repair.
What are some problems associated with sleep deprivation?
Cognitive impairment
Performance impairment
Immune system impairments
What are the two categories of sleep?
REM: rapid eye movement
NREM: non-rapid eye movement
Outline the details of stage 1 sleep.
NREM (light sleep)
1-7mins length
5% total sleep time
Outline the details of stage 2 sleep.
NREM (deeper sleep)
10-25 min length
45% of total sleep time.
Outline the details of stage 3 sleep.
NREM (deepest sleep)
20-40 mins
25% of total sleep time
Outline the details of stage 4 sleep.
REM (dreaming)
10-60 mins
25% of total sleep
What is the VLPO and what is it involved in?
Ventrolateral preoptic and sleep
What areas are involved in awakeness?
Lateral hypothalamic area (LHA)
LDT
PPT
Raphe
LC
What areas are involved in circadian rhythms?
SCN
SPZ
DMH
What is the flip flop switch model? Briefly outline the process.
It is a model that outlines the relationship between Orexin, the vlpo (sleep) and the LC, Raphe (and other awake areas of the brain)
- The activation of one state will inhibit the other.
- Parts of the brain that are involved with staying awake will inhibit the sleep areas (and vice versa).
- Regulated by orexin.
What interaction governs sleep and wakefulness?
The interaction between the homeostatic drive to sleep and circadian rhythm alerting signal.
Describe the graph of the relationship between the homeostatic sleep drive and the circadian drive for arousal.
The sleep drive increases from 7am and peaks at 11pm - steeply dropping until 7am.
The drive for arousal forms a ‘mound shape’ steeply dropping off at around 10-11pm.
This means that as arousal drops, the sleep drive (melatonin production) increases.
Where the arousal drive drops and the sleep drive peaks sleep commences
What are some factors that influence sleep?
Light
Jet lag/shift work
Pain/stress/medical conditions
Medication/other substances
Sleep environment
What is narcolepsy?
A chronic sleep disorder in which sufferers suffer from profound daytime sleepiness.
What is the cause of narcolepsy?
It is caused by disruptions to the brains orexins pathways which is thought to be an autoimmune attack on orexin producing neurons
What is orexin and what receptors does it act on?
It is a neuropeptide produced by a small number of neurons in the hypothalamus.
It acts on a g protein coupled receptor called Hcrtr2
The phenomenon whereby damage to the left side of the brain results in impaired function on the right side of the body is caused by neurons
decussating
The time a molecule takes to move a given distance via diffusion is:
greatest when the molecule can only move in one dimension
Positive feedback is a key feature in which component of the action potential?
Opening of sodium channels
Increased concentration of potassium level in the extracellular fluid around neurones will cause the neurones to
depolarize
the equilibrium potential for potassium becomes more positive so resting membrane potential will in turn become more positive
A technique in which the genome of an organism is modified so that cells express random combinations of several different fluorescent proteins is:
Brainbow
A receptor whose effects can be inhibitory, due to efflux of potassium ions, is the:
GABAA receptor
A disorder characterised by neurofibrillary tangles is:
Alzheimer’s disease
(hyper phosphorylated tau neurofibrillary tangles)
a toxin that blocks voltage gated calcium channels.
Omega-conotoxin
A receptor whose effects are normally inhibitory due to influx of chloride ions is the:
GABAA receptor
(Glycine receptor, part of same superfamily as GABAA)
A receptor whose effects are normally inhibitory due to influx of chloride ions is the:
GABAA receptor
(Glycine receptor, part of same su;erfamily as GABAA)
Channelrhodopsin is derived from what type of organism?
green algae
The “dark current” in rod cells is carried by which ion?
Na+
Martha has a genetic defect that alters her ability to constrict her pupil to light and disturbs her circadian rhythm. This mutation is likely to specifically affect a subtype of which retinal cell?
ganglion cell
what is contained in the inner nuclear layer
cell bodies of bipolar cells, cell bodies of amacrine cells & horizontal cells
what is contained in the outer nuclear layer
rods and cones
a channel protein that is involved in transmission in non-rectifying synapses:
connexin
which ion are the best ion-sensitive fluorescent dyes available?
Ca2+
Marine fish-hunting snails produce the following class of toxins:
Conotoxins
duration of a typical cardiac action potential is approximately:
200 ms
A protein that forms a framework for the generation of intracellular vesicles is
clathrin
The internal diameter of a patch clamp electrode tip is around:
1 µm
optic nerve is made up of axons of which cell type:
Retinal ganglion cells
what are the steps of an inside-out mode patch clamping
- Move electrode onto cell
- Form a seal on the cell surface.
- Pull electrode away from cell
- Move electrode out of the bath solution
photopigment melanopsin is coupled to which signalling pathway?
IP3 via Gq
process by which an odorant is detected by the olfactory system primarily involves what type of receptor?
G Protein Coupled Receptors
A type of drug used to treat multiple sclerosis is:
corticosteroids
A technique that can be combined with the patch clamp to relate the expression level of a protein in a single cell to the function of that cell, is:
RT PCR
How many layers are there in the mammalian cortex?
6
In order for actin to interact with myosin:
troponin must bind calcium
A typical symptom of myasthenia gravis is:
drooping eyelids
In skeletal muscle, the H zone is formed by:
thick filaments
An ATPase protein in skeletal muscle is:
myosin
At synapses in the CA1 region of the hippocampus, entry of calcium via ligand-gated ion channels requires activation of:
AMPA and NMDA receptors
The plateau phase of the cardiac muscle action potential is largely mediated b
calcium channels
an inhibitory postsynaptic potential (IPSP) will result from:
chloride efflux or potassium influx
A light-activated chloride pump, used in optogenetics to inhibit neurons, is
halorhodopsin
When light activates rhodopsin:
phosphodiesterase is activated; sodium channels close
In skeletal muscle the calcium required for contraction enters the cytoplasm via the:
ryanodine receptor
Name 3 past techniques for exploring the structure of the brain.
Brain surgery
Cranial trepanation
Experimental ablation
Briefly outline cranial trepanation and experimental ablation
Cranial trepanation:
- drilling/cutting holes in the skull in aims to heal or be part of a ritual - dates back to 7000 years ago.
Experimental ablation:
- Consists of lesioning or destroying a specific part of the brain to study its function
What is a stereotaxic atlas?
A map of the regions of the brain so that surgeons can locate the exact region for treatment/lesioning.
What are the two ways of producing brain lesioning
Electrode
Cannula
Outline the use of electrode to lesion the brain.
Stainless steel electrode with a conducting element will heat up and destroy nearby cells.
Not very specific lesioning.
Outline the use of cannula to lesion the brain.
It is the use of excitatory aminoacids which are injected into a specific area via a cannula. It is more specific lesioning as they stimulate more specific neurons to death - creating the lesion.
What is a sham lesion?
A placebo procedure that duplicates all the steps of producing a brain lesion except for the one that actually causes the brain damage
What is meant by histological methods?
Refer to a group of procedures (including fixing, slicing, staining and examining the brain) that aim to observe the location of the the lesion
Briefly outline Phineas Gage .
Railroad construction foreman in the US.
Injured by taking an iron rod straight through his head.
This changed him:
- Couldn’t stick to a plan
- became rude, violent and uncontrollable.
First case to suggest a link between brain trauma and personality change.
What does extracellular recording of neuronal cell firing involve?
measures the electrical activity of neurons by detecting the changes in voltage or current outside the cells.
Outline the work of Wilder Penfield.
Used electrical brain stimulation on awake patients for the treatment of epilepsy.
He recorded patient’s reaction when stimulating certain brain areas.
Used this information to create a functional map of the cortex and brain.
- He created the ‘motor homunculus’ as a result of this work
What are some common techniques used in extracellular recording?
single-unit recording, multi-unit recording, and field potential recording
What are 3 electrical recording/stimulation techniques?
Electrophysiology (single/multiple cell recording)
Electroencephalography (EEG)
Deep brain stimulation
What is deep brain stimulation?
Involves implanting electrodes within certain areas of the brain, the level of stimulation is controlled by a pacemaker like device planted under the skin of your upper chest.
What do the electrical impulses of DBS do? What are some pathologies it is approved to treat?
Regulate abnormal impulses.
Affect certain cells and chemicals within the brain.
Approved to treat:
- Parkinson’s
- Obsessive compulsive disorder
- Epilepsy
What is computerised tomography?
It is an imaging technique that combines a series of x ray images taken from different angles and uses computer processing to create cross-sectional images.
What are CT scans used to do?
Pinpoint the location of a tumour
Guide procedures such as surgery/biopsy
Detect and monitor disease such as cancer.
Monitor treatment effectiveness.
In terms of ease and specificity , rank extracellular recording, intracellular recdording & patch-clamp recording
extracellular recording - easy not specific
intracellular recording - hard, specific
Patch-clamp recording - Very hard , very specific
Outline Positron Emission Tomography.
It is a scan that uses a radioactive drug (tracer) to show brain activity.
The tracer is applied which then collects in areas of your body in which there are higher levels of chemical activity.
Outline what MRI is.
It uses a magnetic field and radio waves to create detailed images of the brain.
It is the most frequently used imaging test of the brain and spinal cord.
What is MRI used to diagnose? (7 listed)
○ Aneurysms.
○ Disorders of the eye and inner ear.
○ Multiple sclerosis.
○ Spinal cord injuries.
○ Stroke.
○ Tumours.
○ Brain injury from trauma.
What is fMRI?
functional Magnetic Resonance Imaging.
It measures the metabolic changes within the brain.
What can fMRI be used for?
Can be used to examine brain anatomy in people being considered for brain surgery and it can also be used to assess damage from a head injury or from disorders such as AD
What is gene therapy?
It involves the altering the genes inside your body’s cells to treat or stop disease, instead of using drugs or surgery.
What type of cells does Intracellular recording work well for?
Large cells (50ml to metered or larger)
Outline 3 approaches of using gene therapy.
Replacing a mutated gene that causes disease with a healthy copy of the gene.
Inactivating, or ‘knocking out’, a mutated gene that is functioning improperly.
Introducing a new gene into the body to help fight a disease.
What are two ways in which gene therapies can be applied?
Ex vivo gene transfer (insertion of genetically modified cells)
Direct in vivo injection of viral vectors into the target tissue
Who invented patch clamp recording and what is it
Sakmann & Neher in the late 1970’s
Not a single method, collection of 4-5 diff configurations
Name some commonly used viral vectors for gene therapy.
Retroviral and lentiviral
Adenovirus and adeno-associated virus
Herpes simplex virus
Outline the process of patch clamp recording
Glass tube placed in a heating element, glass softens when heated, pulling electrode apart
End up w/ thin walled glass spike which needs to be sealed onto surface of cell
Take thick sticky resin and tape to end of electrode, dip fine wire into resin solution
Once successfully coated, heat resin and rest to use
Take electrode & put close to a heat source to smooth edges of glass
Use positron electrode on cell
Outline the process of patch clamp recording
Glass tube placed in a heating element, glass softens when heated, pulling electrode apart
End up w/ thin walled glass spike which needs to be sealed onto surface of cell
Take thick sticky resin and tape to end of electrode, dip fine wire into resin solution
Once successfully coated, heat resin and rest to use
Take electrode & put close to a heat source to smooth edges of glass
Use positron electrode on cell
Briefly outline the process of gene therapy.
New gene is inserted into a vector
Vector is injected and enters target cell
New gene is delivered into the nucleus.
(detailed version:)
- New gene inserted into vector which is then injected.
- When it comes into contact with the target cell it will enter through the membrane where it is packaged into a vesicle.
- The increasing acidity causes the release of pentons, and their toxicity breaches the vesicle.
- The virus will then enter the nucleus and disassemble to deliver the DNA into the nucleus.
- Genetic information from the new gene is transferred to mRNA which is now the blueprint for the production of the desired protein.
Outline the function and process of cell attached patch
Record currents through a limited number of active channels at cell surface
Take electrode, manoeuvre to surface of cell, apply gentle suction
Form tight seal between electrode and membrane
Trap channels under puppets to measure activity
Outline stem cells as a treatment.
They provide new cells for the body as it grows, and replace specialised cells that are damaged or lost.
There are three main types:
- Embryonic stem cells
- Adult stem cells
- Induced pluripotent stem cells.
Outline the function and process of whole cell recording
Record currents through active channels in a whole cell- good at seeing cell current responses to drugs
Manoeuvre electrode to surface of cell, apply further suction
Form tight seal between electrode & glass
Trap channels Under pipette
Disrupt membrane trapped under electrode
What are neural stem cells?
Self-renewing population that generates neurons and glia of the developing brain.
They can be isolated, proliferated, genetically manipulated and differentiated in vitro and reintroduced into a developing adult or a pathologically altered CNS.
What is the most common type of patch clamp recording
Whole cell recording
What is a variant of whole cell recording & what is the difference between the two
Perforated patch
Instead of applying further suction, add antibiotic to make perforation in membrane
What are the two main types of memory?
Declarative (explicit)
- Results from conscious effort
Non-Declarative (implicit)
- Results from direct experience.
Give examples of declarative and non-declarative memory.
Declarative:
- facts
- events
Non-declarative:
- procedural skills/habits
- associative memories
Outline the function and process of inside out recording
Record currents through a single active channel away from a cell - good for looking at agents that modulate channel by working at its intracellular face
Start with the same process as cell attached
Trap Channels under electrode , form seal, ** pull membrane away**
Take electrode ** out of bath**
Put electrode back into bath
Outline which areas of the brain are involved in memory and what types of memory they are involved in.
Hippocampus: Involved in explicit memory
Cerebellum and basal ganglia: procedural memory
Amygdala: emotional responses
Many regions of the cortex: Short and long term explicit memory.
What are some limitations in inside out recording
Not very versatile, hard to make a change in this state, hard to set up
What are place cells?
Hippocampal neurons that fire at a high rate whenever the animal is in a specific location in the environment - called the place field.
Outline the function and process of Outside out recording
Record currents through a single active channel away from cell - good for looking at ** agents that modulate channel by working at its extra cellular face**
Start with cell attatched —> whole cell recording
Rip a bit of the membrane off but ** KEEP IT IN THE BATH**
What are cognitive maps?
Internal neural representations of the landscape in which an animal travels.
What are the two states of a channel and What determines them of these states
Open state - determined by K+1(opening rate constant)
Closed state - determined by K-1 (closing rate constant)
Outline the relationship between hippocampus and taxi drivers.
London taxi drivers have greater grey matter in the hippocampus than bus drivers.
- The difference is that taxi drivers have to navigate new routes.
This suggests that spatial knowledge is associated with the pattern of hippocampal grey matter volume.
Why do simple channels have a fairly random pattern of openings and closings even if there is a rate constant
Because rate constants determine probability, but it’s still random
Outline short-term memory.
Last for seconds to hours.
Repetition promotes retention
Limited capacity
‘labile’ - sensitive to disruption
Does not require new RNA or protein synthesis.
If a log frequency is taken of opening and closed times, what would the mean value be
1/ rate constant
What does studying the patterns of opening and closings tell us about
activation mechanisms
Outline working memory.
Used to hold information ‘in mind’
A limited storage store that needs repetition to keep it in mind.
It is the maintenance and manipulation of memory.
What are the 3 things current size depends on
Ion conc
Voltage across membrane
Pore properties
Outline long term memory.
Lasts for days to years.
Unlimited capacity
Consolidated (insensitive to disruption)
Does require new RNA or protein synthesis
Outline the 4 stages of memory.
Sensory stimulus:
- Brain receives information
Encoding:
- Brain transduces and stores information
Storage:
- Brain retains information
Retrieval:
- Brain retrieves information in order to utilise it.
How would you be able to tell if there are at least 3 ion channels when looking at a graph showing current vs time
There would be at least three different levels of current.
Think of it like stairs, if there are at least 3 levels of current , there have to be at least 3 stairs in the staircase. You can’t have a staircase with 3 different heights but only 2 stairs.
What is activity-dependent synaptic plasticity?
Hebbian plasticity
- Neurons that fire together work together.
“When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased” (Hebb, 1949)
What is two electrode voltage clamp and what is often used often in order to conduct them
It is a conventional electrophysiological technique used to artificially control the membrane potential (V m) of large cells to study the properties of electrogenic membrane proteins, especially ion channels.
A common method for expressing proteins of interest is to inject mRNA coding for the protein into the oocytes of the Xenopus Laevis
What is LTP? Outline it.
Long term potentiation.
It is a persistent strengthening of synapses following high frequency stimulation of chemical synapses.
It produces a long-lasting increase in signal transmission between two neurons.
What are two mechanisms of synaptic plasticity?
LTP and LTD
What are the disadvantages of injecting mRNA into xenopus oocytes
RNA is very labile, need to be careful not to degrade it
Two electrode voltage clamp (TEVC)
Xenopus laevis oocytes
TEVC = Xenopus oocytes, THIS IS ALL YOU NEED TO REMEMBER
Outline studies into LTP and what brain region is used.
Slices of the hippocampus are used.
Brief bursts of high frequency stimulation (tetanus) is applied to the CA1 region of the hippocampus.
As a result LTP was induced and the synapses had stronger electrical responses.
Name two glutamate receptors.
AMPA and NMDA receptors
What is FURA-2
A calcium binding dye that when it binds to calcium, changes it’s absorption spectrum
What are calcium sensitive dyes called
Chelators
Outline AMPA receptors.
A glutamate ligand gated ion channel that results in the influx of Na+ into the cell.
What are the two types of spatial resolution in electrophysiology
Local - limited to what we can patch onto
Global (whole neuron, circuit) a don’t have info on what’s going on between local & global level
What is the most important molecule in electrophysiology
Ca2+
What is the structure and polarity of FURA-2
4 carboxylic acid groups
Polar substance - can’t cross cell membranes
Outline NMDA receptors.
They are glutamate ligand gated ion channels.
Require glutamate, glycine and depolarise to open which allows the influx of Na+ and Ca2+.
(extra info)
The increase in Ca2+ in the post-synaptic neuron can then act as a second-messenger to activate intracellular signalling cascades.
- only occurs when the magnesium block in removed via depolarisation
Outline the presynaptic and postsynaptic changes LTP brings about on AMPA and NMDA receptors.
Presynaptic:
- Increased neurotransmitter vesicles
- Increased neurotransmitter release
Postsynaptic:
- Increased dendritic area and spines (increased sensitivity)
- Increase AMPA receptors
What happens to both the emission spectra and absorption spectra when calcium binds/ is added to FURA-2 ?
Absorption spectra- goes from 380nm - 340 nm with a BIGGER PEAK, shift allows us to measure conc of calcium
Emission spectra- stays at 510nm but PEAK BECOMES BIGGER
What are the two morphological changes in dendritic spines due to LTP?
Changes in size:
- Increase in number of neurotransmitter receptors
- Increase in presynaptic vesicles
- Increase in postsynaptic vesicles
Multiple spine boutons:
- Formation of another spine will double the receptors
Both of these are key in LTP as they help to strengthen and increase the electrical activity of these synapses
What are GINA’s and what is an example of one
Proteins
Genetically encoded Ca2+ indicators
GCaMP (calmodulin & M13)
What is LTD?
Long Term Depression:
It is the long lasting decrease of efficiency of synaptic transmission (especially with AMPA receptors)
What is a transgenic animal set up and what is an example of one
The insertion of an indicator into an animal genome to target a particular cell or tissue
Drosophila set up
what are the requirements for fluorescence resonance energy transfer
Two excited fluorophores (one acceptor & one donor) that emit different wavelengths
Close proximity of fluorophores
What causes LTD and what is its role?
It is caused synaptic transmission occurring as the same time as a weak or modest depolarisation of the postsynaptic neuron.
It strengthens the robustness of stored experience by pruning away synapses that are weakly integrated into a synaptic network that stores a specific experience
What animal used halorhodopsin?
Halobacterium (arahchaebacterium)
What colour does halorhodopsin pump chloride at
Yellow or Orange light
Outline how postsynaptic Ca2+ can trigger both LTP and LTD.
A strong depolarisation will lead to high levels of Ca2+ and therefore LTP
A weak depolarisation will lead to little Ca2+ influx and therefore LTD
What does channelrhodopsin respond to in order to open up its channels
Blue light
What causes the production of hyper polarisation by Halothodopsin
Chloride influx
What are some examples of the physiological functions of LTD?
(results from experiments in mice)
- Hippocampus-dependent learning and memory
- Fear conditioning in the amygala.
- Recognition memory in perirhinal cortex
- Cerebellar learning
What does pathway does rhodopsin interact with
Cyclic GMP pathway via transducin
What are some pathological states LTD is involved in?
Psychiatric disorders (e.g., depression, schizophrenia)
Drug addiction
Mental retardation
Neurodegenerative diseases (Alzheimer’s disease)
How do you make a radioligand binding set up
Make radiolabeled version of a ligand that binds to protein of interest
Mix with tissue of interest
measure how much radioactivity has bound to tissue
How do you make a radioligand binding set up
Make radiolabeled version of a ligand that binds to protein of interest
Mix with tissue of interest
measure how much radioactivity has bound to tissue
What are the two types of amnesia?
Retrograde:
- difficulty remembering past information
Anterograde:
- difficulty in learning new information
What are some of the applications of radioligand binding
Measuring amount of binding at diff conc
Screen of new drugs (compare radioligand to competing non-radioactive ligand/drug)
What are some of the applications of radioligand binding
Measuring amount of binding at diff conc
Screen of new drugs (compare radioligand to competing non-radioactive ligand/drug)
Advantages of radioligand binding
Easy to set up
Cheap
Easily scaled
Disadvantages of radioligand binding
Doesn’t tell us what drug does at receptor
Doesn’t have good time resolution
Uses hazardous materials & produces hazardous waste
Outline patient HM.
He had a bilateral medial temporal lobe resection that lead to to anterograde amnesia.
(He had his hippocampus removed which lead to an inability to form new memories)
What is the ability to bend light measures in and how many of these units do the lens and cornea have
Diopters (D’s)
Lens = 12d’s
Cornea = 42 D’s (around 3x)
What do the aqueous and vitreous humour do
Fluid that allows light through but keeps eye structure, apply pressure to keep retina in right place
What is myopia and what sort of glasses lens would be used to counteract it
Short sightedness
Concave lens
What is dementia?
it is a general term used to describe a group of conditions that affect memory.
More than 850,000 people in the UK diagnosed with dementia.
The two main types:
- Alzheimer’s
- Vascular dementia
What is hyperopia and what kind of glasses lens would be used to counteract it
Longsightedness
Convex lens
In terms of shape, how do rods and cones vary
Rods are more long and cylindrical, cones Are rounded
What cells provide signal processing and help ‘reduce noise’
Horizontal and amacrine cells
Outline Alzheimer’s disease.
It is characterised by the presence of intracellular neurofibrillary tangles (tau protein) and the accumulation of extracellular beta-amyloid plaques.
It leads to memory loss and a continuous decline in thinking, behavioural and social skills.
What is the structure of opsins
GCPR’s with 7 transmembrane domains
Outline vascular dementia.
Can be developed after a stroke or it can result from other conditions that damage blood vessels and reduce circulation.
Symptoms vary, depending on the part of the brain affected, but can include problems with memory, reasoning, planning or judgement.
What is retinal a derivative of
Vitamin A
What is the significance of Aplsyia Californica?
It is a sea snail that has been used to understand the link between cellular mechanisms behind memory, learning and behaviour.
Why does the absorption of light cause hyperpolarisation
Causes enzymatic degradation of cyclic GMP into GMP, meaning no cGMP to activate sodium channel so no depolarisation
Name the parts of Aplysia from outside to in.
Parapodium
Mantle shelf
Siphon
Gill
When is trans retinal generated and what does this lead to
When 11-cos retinal absorbs a. Photon of light
Leads to A conformational change in the rhodopsin
What behaviour has been studied in aplysia?
it’s withdrawal reflex.
When a tactile stimulus touches/brushes past the siphon or the mantle shelf, the siphon and gill with retract and the parapodium will cover them to protect them
What does a conformational change of rhodopsin lead to
(In this order)
Transducin activation
Conversion of GDP to GTP
Release of phosphodiesterase
Reduced cGMP
Closure of sodium channels
Why are men more likely to have colour blindness
Red and green opsins both on X chromosome, men only have one X chromosome
What are the 3 types of non-associative learning that occurs in aplysia?
Habituation:
- loss of response due to repeated stimulus.
Dishabituation:
- recovery of an innate response (after habituation)
Sensitisation:
- response stronger than normal (becoming more sensitive to a stimulus
What cells are important for directional motion, modulation of light adaption and modulation of circadian rhythm
Amacrine cells
What are the two types of bipolar cell
On and off
Where does info from the temporal retina go
Does not cross optic chiasma and goes to same side of brain
What are the only output cells in the retina
Retinal ganglion cells
What underlies circadian rhythm and pupillary reflex
Melanopsin
What is similar across species in terms of sensory perception
The periphery of the olfactory system
Where do receptors exist in the human
Olfactory system
Cilia
What are human olfactory receptors classified as
GCPR’s
Outline the experiment on aplysia and what type of learning it displays.
The movement of the gill was recorded to trace the amplitude and response to a specific stimulus.
The researchers would then poke the siphon at different rates to measure the learning.
Results:
- habituation occurred when there was no negative stimulus after the poke.
- dishabituation occurred when there was a shock to the tail after being poked.
This shows classical conditioning
Outline how classical conditioning occurred in the aplysia.
Reflex = unconditioned response
tactile stimulus to tail: conditioned stimulus
shock: unconditioned stimulus.
It was found that when the tactile stimulus was paired with the shock that it brought about a much larger response than if it wasn’t
Outline the process of an AP firing in the human Olfactory system
GDP-GTP exchange
Activates adenylste Cyclase
Breaks down ATP into cAMP
cAMP released & opens gated channels
Calcium & sodium influx
Depolarisation
What is combinations coding in terms of the olfactory system
Ability to encode intensity and diversity of many diff odorants
Why can combinations coding occur in the olfactory system
Each odorant binds to various receptors and activates many neurons
What are the 3 types of papillae
Circumvallate (back)
Foliate (sides)
Fungiform (front)
What are clusters of taste receptors called
Taste buds
Outline how aplysia shows long term memory for habituation.
Over the days of the experiment of the tactile stimulus being applied, the response decreased showing that long term memory has occurred.
may falter after long periods but the response will still be lower than original value before learningn
Where do drosophilas have gustatory neurons
Proboscis, legs & wing margins
What class of receptor are bitter, sweet and umami receptors
GCPRS
T1R1 & T1R3 for umami
T1R2 and T1R3 for sweet
T2R for bitter
What is the class of receptor for sour tastes
TRP channels
Outline how aplysia shows long term memory for sensitisation.
After a period of training (4 days) the aplysia with the tactile stimulus and the shock the response stayed above the original response for up to 26 days.
(the response did decrease over time but it was still above the baseline before learning)
What is the class of receptor for salty tastes
In humans, unknown
In mice - epithelial Na Channel
What are the three levels of analysis for mechanisms for learning?
Synaptic
Biophysical
Molecular
What is the organ that detects pheromones in other animals (not humans)
Vomeronasal organ
What are the 3 fluid filled chambers in the cochlea
Scale vestibuli
Tympani
Scalia media
What structures make up the vestibular system
Semicircular canal
Otolith organs (utricle & saccule)
Hair cells
Why are hair cells ionotropic
Structure of the cochlea
What is mechano-transduction
Direct form of transduction that occurs very quickly due to no electrical component being required
In the 5 sense, which on functions by the hyperpolarisation of its receptor cells due to transduction current
Vision (Na+)
Outline presynaptic facilitation of sensitisation as a synaptic analysis in aplysia.
Sensitisation to the input (tail shock) causes spike broadening, leading to an increased duration of the AP on the sensory neuron leading to more neurotransmitter release and an increased excitatory postsynaptic potentials.
What are the 3 main types of muscle
Skeletal, cardiac, smooth
What are the two main body functions of skeletal muscle
Movement, heat generation
What is the connective tissue that covers a muscle fibre called
Endomysium
What is the cell membrane of a skeletal muscle called
Sarcolemma
What is the grouping of muscle fibres into bundles in skeletal muscle called
Fascicles
What is the epimysium
Outside protective sheath that covers the endomysium in skeletal muscle
Outline the importance of serotonin in sensitisation in aplysia.
Serotonin acts on the sensory neuron causing increased sensory neuron excitability, increased motor neuron excitatory post synaptic potentials and therefore a higher reflex amplitude (which is what characterises sensitisation).
Outline the structure of muscle fibre
Bundles of filaments called myofibrils
Myofibrils composed of filaments called myofilaments
T-tubules that lean from sarcolemma into interior of skin
Plasma membrane - sarcolemma
Endoplasmic reticulum (sarcoplasmic reticulum) wrapped around myofibrils
What is a triad formed of
Terminal cisterns interacting with t-tubules
Which types of muscle are striated
Cardiac and skeletal
Outline the biophysical analysis of the sensory neuron in relation to sensitisation in aplysia.
- Serotonin temporarily closes potassium channel (S current) in sensory neuron.
- Outward potassium current is slowed.
- Repolarisation of membrane potential is slowed -> spike broadening
- Increase calcium influx.
- Increase in transmitter release.
- Enhanced excitability
What is the sarcomere &
What are it’s two major structural gestures
Repeated myofibrils unit
Thick filaments - composed of myosin and titin
Thin filaments - composed of actin and nebulin
What is the sarcomere &
What are it’s two major structural gestures
Repeated myofibrils unit
Thick filaments - composed of myosin and titin
Thin filaments - composed of actin and nebulin
What is the largest protein in the human genome
Titin (3rd most abundant too)
What is the H-zone made up of in the sarcomere
Thick filaments only
What is the I- band made up of in the sarcomere
Thin filaments only
What is the A band made up of in the sarcomere
The overlap of thick and thin filaments
When does the sliding filament mechanism operate
When there is optimal overlap between actin and myosin
What is the structure of myosin
Hexameric
Formed of two heavy chains and 4 light chains
What are the two types of light chain in myosin
Regulatory and essential
How many different kinds of myosin are there
9
8 in skeletal and cardiac muscle
1 in smooth
What does the myosin head have
Built in ATPase activity
What are the two forms of actin
Globular - g actin
Filamental - f actin (the one found in muscle)
Outline the molecular analysis of sensitisation in aplysia.
Serotonin binding to the sensory neuron increases the levels of cAMP.
cAMP acts as a secondary messenger, activating PKA in the cytoplasm of the cell.
PKA’s actions lead to spike broadening and enhanced excitability (sensitisation)
How many actin are there per tropomyosin
One tropomyosin per 7 actin monomers
How many actin are there per tropomyosin
One tropomyosin per 7 actin monomers
what is troponin and what are the three types
Trimeric complex associated with tropomyosin and actin
Troponin T- associates with tropomyosin
Troponin I - associates with Actin, inhibits formation of cross bridges
Troponin C- binds calcium
Outline the process for long term memory for sensitisation.
1.Repeated serotonin or cAMP applications
2. Persistent phosphorylation of preexisting proteins and synthesis of new proteins.
3. Long-term increase in synaptic facilitation
4. Long-term increase in synaptic transmission
5. Dramatic growth of sensory neuron processes.
6. LONG-TERM MEMORY FOR SENSITISTION
How does long term sensitisation effect neurons synapses?
Habituation will decrease boutons
Sensitisation will increase boutons
