Unit 1 Flashcards
What is trepanation?
a surgical intervention where a hole is drilled into the skull exposing the duramatter
- aka a craniotomy
What is a trepanation where the bone isn’t replaced?
craniectomy
What is a trepanation/craniotomy used for?
- used to relieve pressure and treat health problems -surgical access for intracranial pressure monitoring
- to treat epidural and subdural hematomas
What is a hematoma?
- a solid swelling of clotted blood
What is the brain made of?
network of neurons and glia
How do neurons communicate?
-electrical and chemical signals
What is the neuronal pulse called?
AP
What is aphasia?
partial or complete loss of language abilities
Which aphasia is known as fluent or sensory aphasia?
Wernicke’s Aphasia
What are the symptoms of Wernicke’s aphasia?
- fluent speech that makes no sense
- poor comprehension
Which aphasia is known as motor aphasia, non-fluent aphasia, or production aphasia?
Broca’s Aphasia
What are the symptoms of Broca’s aphasia?
- non-fluent speech, struggle to produce words
-telegraphic (agrammatical) - speech makes sense
- good comprehension
What do the different types of aphasia prove?
localization of function
What is localization of function?
- different areas of the brain control different functions
How does aphasia prove localization of function?
- damage in the different areas of the brain have different results
Where does wernicke’s aphasia occur?
- temporal lobe
Where does broca’s aphasia occur?
- frontal lobe
-cerebral cortex
What is a stroke?
- a rapid loss of brain functions due to a loss of blood supply
What are the types of strokes?
-ischemic
-hemorrhagic
What is an ischemic stroke?
- a blockage of blood supply
What is a hemorrhagic stroke?
blow out to blood supply
What are transient ischemic attacks (TIAs)
- mini strokes
What are the symptoms of a stroke?
-depends on the area of the brain it effects
What did Camillo Golgi do?
- developed the Golgi stain
- reticular theory
What did Ramon y Cajal do?
- grandfather of neuroscience
- neuron doctrine
- discovered the synaptic cleft
How wide is the synaptic cleft?
20 mm wide
What is the site of synaptic contacts?
dendritic spines
Are all axons milenated?
no, but most are
What does myelin do?
- increases speed at which AP travels down the axon
What are the non-neuronal cell types?
-mast cells
- microglia
-macroglia (everything below= micro)
- astrocytes
-oligodendrocytes
-radial glia
-Schwann cells
-satelite glial cells
What are astrocytes?
- chemical environment regulation
- buffer extracellular K+ levels
- modulate and control blood flow in the brain
- CNS
-sucks up K+
What are Mast cells?
- Immunoactive cells in the CNS
What are microglia?
- specialized macrophages
What are oligodendrocytes?
myelin
CNS
What are radial glia
-neuron progenators
-stem cells
- scaffolds
-highways
-CNS
What are Schwann cells?
-myelin in the PNS
What are neuronal circuts?
- a population of neurons interconnected by synapses and supported by non-neuron cells
What do neuronal circuits do?
- carry out specific functions when activated
-underlies all functions of the nervous system
-simple or complex
How do neuronal circuits work?
- input- processing- output
-afferent to efferent
What are examples of simple circuits?
- stretch reflex (knee jerk)
- leg withdrawal reflex
What do efferent signals do?
- carry nerve impulses away from the CNS
What do afferent signals do?
- carry nerve impulses from receptors/sense organs towards the CNS
What is a seizure?
-abnormal neuronal activity
What is epilepsy?
- chronic condition of repeated seizures
What is an EEG and what does it do?
-electroencephalography
- measures brain electrical signals
How does an EEG work?
- shows voltage fluctuations from ionic current flows by large groups of neurons
- displaying synchronous activity by many neurons in similar spatial orientation
What is an EMG and what does it do?
- electromyography
-measures muscle signals
What is an EKG and what does it do?
- electrocardiography
-measures heart signals
What is a current?
energy flow between one area and another
What are seizures caused by?
chronically overexcited neurons
- you can see them on an EEG even when they aren’t happening
What are the surgical treatments for epilepsy?
- remove the focal point
- remove the corpus callosum
What does removing the corpus callosum do for seizures?
- limits how seizures spread because the two sides can’t communicate
What do drugs do for epilepsy?
- cause a use-dependent increase in the inactivation time of voltage-dependent Na+ channels
-Enhance GABAergic inhibition
Does an axon’s membrane have a charge?
yes
What does a membrane’s charge do?
- allows for AP to be induced and for APs to travel down the axon without a loss of signal
What has to happen for signals to be transmitted across the axon’s membrane
-ions must cross the membrane
- membranes are too thick for ions to flow through so Ion channels are neccessary?
Do all ions flow in the same direction?
- no
-Different ions flow in different directions
What are the key characteristics of ion channels?
- they are specific for particular ions (element, not just charge)
-integral membrane potentials - they can open and close
- don’t physically ions, they move down a gradient
How do ions move through the ion channels?
- Move passively down a gradient
-Electrical and chemical gradients
-Different ions move in different directions across the membrane
-ions travel in the direction of the electrochemical gradients
What is membrane potential?
- the difference in electric potential between interior and exterior of the cell
-what you measure
What dictates the direction an ion flows?
- the driving force and the concentration/electrical gradients
If an ion is positively charged and the gates are open what would happen to the membrane potential?
- membrane potential would be more positive
If an ion is negatively charged and the gates are open what would happen to the membrane potential?
- would become more negative
What is Vm
membrane potential
What does more ions do to the driving force?
-more ions= stronger driving force
What is equilibrium potential?
- membrane potential where the ion is at electrochemical equilibrium
- for a single ion
-when concentration and electrical driving forces are equal and opposite
What is wrong with the Nerst equation?
- it doesn’t equate forpermeability
- Most neurons are permeable to more than 1 ion so Vm doesn’t normally match Eion
What is the typical mammalian membrane potential?
-40 - -90
How many ions move to generate membrane potential?
- very few ions move to generate membrane potential
- no immediate effect on the concentration gradient
- over a long time (especially in active neurons) Na+ and K+ can run down
Does the NaK+ Pump actively drive AP?
no
What drives AP
ion channels
What does the NaK+ pump do?
plays an important role in maintaining concentration gradients OVER TIME
What are ion transporters?
- integral membrane proteins
-selective for specific ions
-actively moves ions across the membrane - moves ions opposite to the concentration gradient
What cells regulate K+
- astrocytes buffer extracellular K+ levels
- they link together to widely regulate K+
How does astrocyte-neuron communication through Calcium and gliotransmitter signaling in the tripartite synapse work?
-gliotransmitters leave astrocyte through transporter and bond to their receptor on the neuron
- neurotransmitters leave the neuron and bind to gq proteins on astrocyte
- Inside the astrocyte PLC is coming through GQ protein
- pLC to PIP2 to IP3 to ER to Calcium
-glial cells can regulate extracellular milieu and buffer K+
What is AP controlled by?
-voltage-gated ion channels
-ion permeability and conductance
- current flow
-inactivation of voltage gated channels
What is ap conduction influenced by?
- passive and active components
-myelin
When does undershoot occur?
after repolarization
What is hyperpolarization?
-when the membrane doesn’t immediately return to resting potential bc voltage-gated channels are open
- K+ is flowing out through leak channels and since K+ is flowing out the positive ion is leaving the membrane becomes more negative
How does the membrane go back to normal after the undershoot?
leak channels
What is overshoot?
- When membrane potential reaches the positives
-doesn’t quite reach Na+ potential bc K+ channels kick in and the voltage channels overlap - Na channels close and K+ starts leaving
What is the rising phase?
- when Na+ and K+ channels are open
-Na+ flowing in is what makes the membrane less negative, depolarizing it
-once rising for a little while before it can start again
What is the falling phase?
- where re-polarization is happening
- K+ is flowing out of the cell
- K+ pumps have been on the entire time just too slow to cause a response until now
- Since K+ is slower it helps control AP and allows cell to be open longer
What are the phases of AP?
- Threshold: K+ going in and out at an equal rate
- Rising: K+ going out, Na+ going in
- Falling: K+ going out only
- Threshold
What mediates the rising phase?
- voltage-gated Na+ channels
- these are different from leak channels open at rest
What are the advantages of the voltage-gated channels?
-can open and close very fast
- has an ion-selective pore, a voltage-gated sensor that opens the pore via an activation gate in the pore and an inactivation gate separate from the voltage gate
- once it opens it can’t open again until it repolarizes to a negative voltage
What mediates the falling phase?
-voltage gated K+ channels
What are the ways to graph the changes during AP?
-membrane potential (vm)
- ionic permeability or conductance’s
V=IR
V=I(1/g)
1/g=R
What does depolarization do to K+ channels?
- Voltage-gated K+ channels are activated by depolarization but are much slower to open than Na+-gated channels
How many different types of voltage-gated K+ channels?
lots
Does K+ have an activation gate?
- yes activation gate
-some have deactivation gate
What is the AP positive feedback loop?
- AP is all or none
- depolarization
-opens voltage-gated Na+ channels - Na+ influx is greater than K+ efflux
-more depolarization
-threshold
What is threshold?
- membrane potential at which Na+ influx overcomes K+ efflux resulting in at least 1 AP
How does the brain slice technique work?
- take a thin slice out of a rats brain
- keep it as alive as possible in the petri dish
-typically studies caudut/putman area and nucleus accumbens
What does Putman area control?
- motor control
What does the nucleus accumbens control?
reward and motivation
What are the types of patch recordings?
-voltage clamp
-current clamp
- dynamic clamp
What does a voltage clamp measure?
current changes
What does a voltage clamp manipulate
voltage
What is the clamp formula?
V=IR
What does a current clamp measure?
voltage changes
What does a current clamp change?
current
What does more depolarization lead to?
more AP
Do all neurons respond the same to depolarizatoin?
no
-they have different types and densities of ion channels
What does an inward current mean?
- a positive current is going into the neuron or a negative one is coming out
What does resistance measure?
-if things are open
What is resistance measured in?
conductance
What is an absolute refractory period?
when an AP cannot be generated
What does the absolute refractory period look like on the ionic basis?
- inactivated V-gated channels
What is the relative refractory period?
harder to generate AP, but still possible
What does the relative refractory period look like on?
some voltage-gated K channels tend to keep the membrane closer to Ex and farther from the threshold, maybe a few Na channels are still inactivated
What does one class of epilepsy drugs do?
-causes a use-dependent increase in the inactivation time of the voltage-dependent Na+ channels
-extends refractory time
-means its closed for longer and can’t hyperfire
-harder to generate AP
What is the drawback to epilepsy drugs?
- slower movements and reaction time
What is AP propogation?
- AP must travel from azon hillock to terminals
Do APs cross the chemical synapse?
no only chemicals do
How do APs regenerate?
- Depolarization causes AP on one side of the membrane, which causes another Ap depolarization nearby…
- this is a high fidelity process that can almost perfectly copy and go over and over
Is AP generation a passive, or active current flow?
a passive current flow that decays with distance
Do Aps move in both directions?
not often
Why don’t APs move in both directons?
- because voltage-gated Na+ channel inactivation, takes time to regenerate
-if an AP has already happened, even if you injected a current it wouldn’t flow in both directions
What happens if you inject a current before an AP happens?
it would open Na+ channels and cause AP to fire
- in this case it would go bothways
What does myelin do (what is saltatory conduction)?
makes ap go faster because it lets them jump to other parts of the axon and skip regenerating AP
What are the nodes of ranvier
unmyelinated, specialized region of the axonal membrane
-includes the highest density of voltage-gated ion channels on axon
What is MS?
- neurodegenerative disease of oligodendrocytes in CNS
-autoimmune disease
Why do signs and symptoms of MS differ?
-localization of function
-degeneration
Is there a cure to MS?
no
What are the movement symptoms of MS?
-numbness/weakness in 1+ limbs
-Typically 1 side at a time (l,r,u,d)
-electric shock with certain neck movements (especially bending foward)
- tremor
- lack of coordination/unsteady gait
What are the vision symptoms of MS?
- partial/complete loss of vision
- usually one eye at a time
- pain during eye movement
- prolonged double vision
- blurry vision
What are the misc. symptoms of MS?
-slurred speech
-fatigue
- dizziness
-tingling/pain in the body
- problems with sexual, bowel, bladder functions
How does passive current move across the axon?
-moves down the axon
-less current loss across the membrane and capacitance is increased
What are the three regions that are defined by axial glial interactions at the nodes of Ranvier?
- adjacent paranode (PN)
- juxta perinodal region (JP)
(contains delayed rectifier K+ channels) - Internode
Do the nodes of Ranvier have Na+
yes, Na+ rich
How is the axon domain regulated?
- by soluble signals from myelinating glia and direct contact and interactions between proteins expressed on the surface of axons and glia
Does the myelin sheath have plasma?
- very little cytoplasm between the plasma membrane that makes up the sheath
- this creates a thicker membrane especially with regard to its electrical properties
Do glial cells influence AP?
yes, through myelination
-can direct localization of membrane proteins in neurons including ion channels
How do AP and calcium affect NT realeas?
- AP depolarizes terminal which leads to an influx of Ca leading to vesicular fusion and NT release
How do we know vesicular fusion is a thing?
- we can measure vesicular fusion, NT release on the presynaptic neuron, and NT binding on the post synaptic neuron
What do SNARE proteins do?
- help dock vesicles in place
Where are V-Snares?
-vesicular membrane
What is an example of a V-snare?
synaptobrevin
Where are t-snares?
terminal membrane
What is an example of t-snares?
- syntaxin
-SNAP 25
How can you stop NT action?
- diffusion
-enzymatic degradation - reuptake
When is enzymatic degradation common?
- protein NTs (neuropeptides)
-ACH
When is reuptake common?
- small molecule NTs that are actively taken back from the synaptic cleft by the presynaptic terminal or peri synaptic glial cells?
What do electrical synapses allow for?
- direct ion flow
-fast but dumb
-direct current flow from one neuron to another
-bidirectional ion flow
-synchronization of many neurons
How do electrical synapses allow for direct ion flow?
- through gap junctions formed by connexions
- allows for moderately sized compounds through
Where are electrical synapses found?
- coordinates movements of gut, respiration, brainstem
What are drawbacks to electrical transmission?
- bidirectional, less versatile, signal not amplified, polarity can’t change,
less potential for modulation
Do chemical synapses have a physical gap?
- yes
-synaptic cleft
Where is the synaptic cleft?
- in chemical synapses, between presynaptic and postynaptic cell
How can you tell the difference between pre-synaptic and post-synaptic cleft?
- presynaptic is denser than post synaptic
Where does the info for chemical synapse come from?
- neurotransmitters that cycle in the synaptic cleft
What is a drawback to a chemical synapses?
- slower than electrical
-smart but slow
Where are astroglia found?
CNS
Where are schwann cells found?
PNS
How many chemical signals can a single synapse release?
multiple
What are the types of chemical signaling in order of slowest to fastest?
- classical endocrine
-paracrine signaling - autocrine signaling
-synaptic transmission
What is classical endocrine signaling?
- hormones in blood stream to reach target
What does paracrine signaling target?
nearby things
What does autocrine signaling target?
- the thing that secreted it
What is the NT cycle in the synaptic cleft?
reserve
ready pool
release
refill
What does synaptic transmission target?
NT at synapse, very close range things
What are neuropeptides?
- NT
-some act as hormones in 1 context, NTs elsewhere
How long are neuropeptides?
3-36 amino acids
What are examples of neuropeptides?
- enkephalines,
-substance P
-somatostatin
-CART
Where are neuropeptides synthesized and packaged?
- dense core vesicles
What are the types of small molecules?
-monoamines
-ACH
-amino acids
-purines
What are examples of monamines?
- serotonin, histamine, octopamine, catecholamines
What are examples of catecholamines?
- dopamine
- epinephrine
-norepinephrine
What are examples of amino acids?
- glutamate
-GABA
-glycine
-asparate
What are examples of purines?
-ATP
-Adenosine
Describe NTs?
-packaged synaptic vesicles
- NTs
How are neuropeptides made?
- synthesized like all other proteins in the cell then transported to terminal
How are small molecules made?
- only made if necessary, packaged in the terminal and some in the vesicle
What is anterograde transport?
- from soma to axon terminal
-depends on kinesin
What is retrograde transport?
-axon terminal - soma
-depends on dynesin
How is ACH packaged?
-packed in vesicles
-proton pump generates a proton gradient and across a vesicle membrane
-ach transporter uses energy from proton gradient to move ACH into the vesicle
How is ACH stopped?
- degraded in synaptic cleft by ACHE
How is ACH recycled
-choline is transported into the terminal
-choline is used to make more ACH
What does too much choline cause?
- hypotension and liver damage
What is serotonin uptook by?
serotonin transporter
Where is serotonin repackaged or degraded?
presynaptic terminal by MAO
What is GABA uptook by?
- selective uptake by GABA transporters and glutamate transporters
Do GABA and glutamate require synthesis in the neuron?
no
-usually packaged outside using Na+ as the energy source
How do GABA and glutamate transporters get their energy?
- proton gradient
What type of transporters are GABA and glutamate?
- vesicular
What is excitation?
- post-synaptic neuron is more likely to fire
-depolarizes
What is inhibition?
makes postsynaptic neuron less likely to reach threshold (voltage) in the postsynaptic nueron
What is postsynaptic potential?
- change in membrane potential in the postsynaptic neuron
What clamp is postsynaptic potential?
- current clamp
What is Excitatory Postsynaptic Potential?
-input makes the postsynaptic neuron more likely to reach threshold
What is an inhibitory postsynaptic potential?
-input makws the postsynaptic neuron less likely to reach threshold
What are postsynaptic currents?
- change in membrane current in the postsynaptic current (recorded in voltage clamp)
What do potentials and currents look like on a graph?
-curves
What does a downward deflection on a current mean?
-positive ions in or negative out
how can you test which ions carry current?
- removing the ion from extracellular fluid
How is ACH broken down?
ACHE
What happens if you switch from current to voltage clamp?
-depiction flips
Is ENa excitatory or inhibitory?
-typically excitatory because it is above threshold
- the potential is depolarizing bc membrane potential is hyperpolarized
If CL had its way which way would membrane potential move?
- towards hyperpolarization bc it has a negative equilibrium potential
What is the reversal potential for a synapse?
- membrane potential of a post-synaptic neuron (or another target cell) at which an NT causes no net current flow
- equilibrium potential, but for a synapse
What determines postsynaptic excitation and inhibiiton?
- reversal potentials
-threshold potentials
What determines reversal potential?
- what ions can flow
What happens if the reversal potential is more positive than threshold?
- excitation occurs
What happens if the reversal potential is more negative than threshold?
- inhibiton occurs
What is an excitatory synapse?
- a synapse in which the current resulting from activation of a ligand-gated ion channel has a reversal potential that is depolarized compared to threshold
What is an inhibitory synapse?
- a synapse in which the current resulting from activation of a ligand-gated ion channel has a reversal potential that is hyperpolarized compared to threshold
How does synaptic integration work?
- a neuron receives input from hundreds of thousands of synapses
- All active inputs and intrinsic properties are taken into account at the axon hillock
- if threshold is reached, an AP is fired
Where does voltage of the membrane need to hit threshold?
- axon hillock
Is the immediate effect of synaptic integration on the membrane at each synapse local or far-extending?
local
Does synaptic integration amplitude decrease with distance?
yes
Does AP decrease with distance?
no
What does synaptic integration amplitude depend on?
internal and membrane resistance
How is AP generated before the axon hillock?
-mostly passive current
What is spatial summation?
- inputs combined across nearby spaces
What is temporal summation?
- inputs combined bs they occurred close in time
How does driving force change?
- ions, membrane potentials
What is neuromodulation?
- the physiological process by a given neuron uses one or more neurotransmitters to regulate large and divers populations of neurons
How is neuromodulation different from classical synaptic transmission?
- in classical a presynaptic neuron directly influences a single postsynaptic partner and in modulation a large and diverse population is controlled
What are examples of neuromodulators?
-dopamine
-serotonin
- ACH
- histamine
Can neuromodulators bind to ionotropic receptors?
yes but they don’t have to
Describe NT receptors?
- highly specific for a given NT
-each NT has many different receptors
-receptor determines the effect of the NT
-ionotropic or metabotropic
-localized to different areas
Where are NT receptors localized to?
- postsynaptic membrane (always)
- presynaptic membrane (sometimes)
- peri synaptic glial membrane (usually, maybe always)
Describe ionotropic receptors?
- ligand (NT) gated receptors
- open within 1/2 a msec
- usually 4-5 protein subunits each with 4 transmembrane domains
-ion channels
-different combos of subunits lead to different subtypes of that receptor
What subunits bind to the AMPA receptor?
-GLUTAMATE
-glu 1-4
What subunits bind to the NMDA receptor?
- NR1, NR2A-D
What subunits bind to the Kainate receptor?
- glu R5-7
-ka1+ka2
What subunits bind to the GABA receptor?
a 1-7
b 1-4
Y- 1-4
8 looking thing
epsilon
P1-3
What subunits bind to the glycine receptor?
a1-4
b-4
Y
8 looking thing
What subunits bind to the serotonin receptor?
5HT3
What subunits bind to the purine receptor?
P2x1-7
What are agonists?
drugs that bind to a receptor and mimmick the effect of the natural NT
What are examples of agonists?
- NMDA, AMPA, Muscarine, Nicotine
What are glutamate receptor agonists?
- NMDA receptors
-AMPA receptors
What are the ACHR receptor agonists?
-muscarine
-nicotine
What are antagonists?
- bind to the receptor and block the normal activity of the ligand
What are examples of glutamate receptor antagonists for the NMDA and AMPA receptors?
-AP5 and CNQX
Whatis atropine?
MACHR antagonist
What is curare?
- NACHR antagonist
What does glutamate do?
depends on the receptor it activates
What are the three glutamate receptors?
-kinate
-AMPA
-NMDA
What is the ampa receptor?
-gated by glutamate
-allows cations to flow in and out of the neuron
- principal gated ions are NA and K+ in the typical ampa receptor
What is the NMDA receptor?
- ion channel that is gated by voltage and glutamate and low levels of glycine
-very useful for ion channel causing long term changes inside of the postysynaptic neuron
What must happen for NMDA to bind?
-glutamate and glycine must bind
- strong depolarization of the postynaptic membrane
Describe the effects of AMPA and NMDA together?
Glutamate binds to AMPA and NMDA
- N+ and Ca2+ now also flow through NMDA receptors. This further depolarizes the membrane and triggers signal transduction pathways
which recruits other ion channels and changes the ene expression inside the postynaptic neuron
Describe gaba?
- usually inhibitory
-a variety of drugs alter the effect of GABA when binding to its receptor - some neurosteroids do the same thing naturally (paracrine signaling)
What is a neurosterioid?
- hormone produced inside the brain by neurons or glia
Describe metabotropic receptors?
-monomeric
-pharmacology defines receptor subtypes
- no ion channels
-g-proteins couple effector systems
- slower (30ms-1s)
-one or more change leads to changes in mebrane permeability and or altered cellular metabolism through secondary messengers
-each gene codes a specific receptor that will dictate what happens
Describe cholinergic receptors?
-agonist: nicotine and muscarine
-antagonist: curare and atropine
- nicotine ACHR typically allows N+ and K+ ions to flow
- curare is a Nachr antagonist and paralytic bc neuromuscular junction is being blocked by Curare which is an antagonist blocking its functions
