Lectures 1-7 Flashcards
What is cranial or anterior?
head
what is posterior or caudal?
tail
what is dorsal?
back
What is ventral?
stomach/front
what is medial?
down da middle
what brain region do only mammals have?
neocortex.
where does information come from for the somatic/autonomic PNS?
somatic: skin, muscles & joints.
autonomic: smooth muscles - blood vessels and glands.
how is the autonomic system divided?
sympathetic - uses energy.
parasympathetic - conserves energy.
describe the spinal cord.
CNS.
protected by the spinal column, surrounded by meninges and CSF.
primary channel for messages from skin joints & muscles to/from brain.
dorsal roots of the spinal cord contain sensory afferent neurons.
Ventral roots contain motor,
efferent neurons.
What is white and grey matter?
Grey matter = neuron cell bodies
White matter = myelinated axons
Describe the neural tube.
Three layers of cells: endoderm (linings of organs; viscera)
mesoderm (bones and muscles)
ectoderm (nervous system and skin)
CNS develops from the walls of the tube. PNS derives from
the neural crest.
Describe spinal bifida.
Failure of the posterior neural tube to close.
• Supplementing diet with folic acid in early pregnancy can reduce neural
tube defect incidence by 90%.
Where else is CSF in the body?
the brain is hollow and bathed in CSF.
Describe the regions of the brain roughly.
??
prosencephalon/forebrain - telencephalon.
diencephalon.
mesencephalon/midbrain
thalamus/hypothalamus
rhombencephalon/hindbrain.
pons/medulla/cerebrum
Describe the brainstem
Oldest part of the brain – decision matrix. Controls vital functions.
Contains:
• Midbrain – movement, sensory input: eyes, ears
(hind brain:)
• Pons – ‘switchboard’ connects - Cerebellum to Cerebral cortex
•Medulla – autonomic functions
•(Cerebellum)
Describe the pons and medulla.
Pons: swells out from ventral surface of brain stem. Important relay between
cortex and cerebellum.
Medulla: important in control of blood pressure and respiration.
What is decussation?
To cross or become crossed so as to form an X.
The corticospinal tract crosses over in the medulla.
• Right hemisphere controls left of body
• Left hemisphere controls right of body
Describe the cerebellum.
An ‘old’ part of the brain. • Movement control centre. • Extensive connections to cerebrum and spinal cord. Contains at least as many neurons as both cerebral hemispheres! • Diseases include ataxias – aberrant movement coordination.
Describe the Diencephalon & Mesencephalon.
Midbrain: linkages between components of motor systems (e.g. substantia
nigra), eye movements.
Diencephalon: thalamus (relay and gating roles) and hypothalamus
(homeostasis and reproduction)
Describe the Cerebral cortex.
Controls:
•Voluntary actions
•Cognition
•Perception/awareness
Mammals have a more complex 6-layer structure of the cortex =
neocortex.
Highly developed – No. of neurons related to “intelligence”.
Different sizes, same general structure.
Why does Cortical folding occur?
Problem:
• To increase intelligence need to increase processing
power
• Cortical neurons represent processing power
• = increase number of cortical neurons
But:
• Skull is confined structure, want to keep volume +
mass to minimum.
• Big heads harder to protect than little ones!
So fold for larger surface area.
Describe the regions: Frontal Parietal Occipital Temporal
Frontal - front
Parietal - middle
Occipital - back
Temporal - underneath
What is the homunculus?
A way of showing the location and amount of neocortex dedicated to a
particular function.
• Proportional to neuronal composition not to the mass of the body part!
• Highlights the importance of controlling finger movements and speech in
humans.
What is EEG?
Electroencephalograms.
Measure “Brain waves” corresponding to activity
Fast, cheap
Hard to interpret, poor resolution
What is CT?
Computed tomography, x-ray radiation.
What is MRI?
Magnetic resonance imaging.
A strong magnetic field and radiowaves.
• Non-harmful and very detailed.
• Useful for soft tissue.
– Expensive!
What is PET?
radioactive isotopes/glucose used to highlight high metabolic activity from positron emissions.
What is fMR?
oxygenated haemoglobin has a different magnetic resonance than deoxyhaemoglobin.
Describe Cajal and his neuron doctrine.
neuron doctrine - each neuron is a discrete cell.
principle of dynamic polarisation - electric signals will only travel in one direction.
principle of connectional specificity - not random connections.
Why is the electron microscope dope?
Can examine cell ultrastructure
Confirmed existence of synapses
Disadvantage: cells fixed i.e. dead
Describe fluorescent labelling.
Prepare selective antibody (or drug), tagged with fluorescent label.
Add to tissue and allow to bind strongly.
Target protein in tissue.
Wash off any free labeled antibody (or drug).
Image distribution of fluorescence.
Disadvantage: limited by range of antibodies available.
Describe confocal microscopes.
Lasers, High sensitivity cameras Imaging software •Can examine live cells •Physiology • Disadvantage: modest resolution 0.1μm
What are the two cell types in the nervous system?
neurons & glia.
Describe glia cells.
•Outnumber neurons by factor of 10:1. •May mediate some signalling in brain. •Primary role is to support neurons. •Can divide (unlike neurons). can produce myelin
What are astrocytes?
- Majority of glia
- Starshaped
- Fill space between neurons
- Regulate composition of extracellular fluid
New research: astrocytes can play an important role in directing the proliferation and differentiation of neural stem cells.
Describe oligodendrocytes/schwann cells.
glia Myelinate axons of neurons. Oligodendrocytes = CNS, many axons. Schwann cells = PNS, single axon
Describe microglia and ependymal cells.
Microglia act as the brain
scavengers:
phagocytic/immune function.
They can migrate.
Ependymal cells line ventricles and also direct cell migration during development of the brain.
Describe neuronal structure.
Highly polarised.
Soma - cell body.
Axons - specialised for transmission of information.
Dendrites- specialised for receipt of information
In common with all cells:
• Cell body with cytosol and organelles
including a nucleus.
• Cell membrane (plasmalemma)
Unique(ish) to neuronal cells:
• Cannot reproduce.
• Can trigger action potentials (excitable cells! Although some others can too).
No ribosomes in axons!
How to get protein from soma to axon terminal?
What are the roles of the neuronal cytoskeleton?
•Structural support – shape and calibre of axons and dendrites •Transport cargo to and from axons and dendrites •Tethering of components at membrane surface
Describe microtubules, neurofilaments and microfilaments.
Microtubules:
made of tubulin, polymerise to grow
Run longitudinally down axons and dendrites
Big, 20nm wide, tubulin polymers
Polymerisation/Depolymerisation – shape change
Microtubule Associated Proteins e.g. MAP-2, Tau
Role: Structural and Transport
Kinesin & Dynein
Neurofilaments:
10nm wide filamentous protein threads
Role: Mechanical strength
Microfilaments: made of actin 5nm wide, actin polymers Tethered to membrane Role: Mediate shape change
what are the types of neurones in terms of shape?
unipolar, bipolar, multipolar.
Based on morphology or number of processes
coming from the cell body.
What are the types of neurones in terms of function?
Sensory (afferent; somatic or visceral) neurons originate
from sensory receptors to the ‘processor’.
– Motor (efferent; somatic or visceral) neurons conduct
signals that originated in the CNS.
– Interneurons are between sensory and motor neurons.
Describe how abnormal neuronal cells can affect people? (2 examples)
•Proximal dendrite malformation correlates well with severity of retardation.
Alzheimers, dead/dying neurones, Tau removes neurofilament structure.
What is an ion?
An ION is any atom or molecule that has gained or lost one or more electrons Ions, are by definition CHARGED
Why is water unique?
hydrogen bonds.
solid is an organised lattice.
at liquid bonds are randomised, it is denser.
What are some uses of ions?
Carry signals in the body
action potentials.
Act as an energy store
secondary active transport.
Interact biochemically with proteins and other molecules
Ca2+/troponin C in muscle contraction
Mg2+/ATP
Describe ionic size and the hydration shell.
Hydration shell affects mobility in solution
Hydration shell is the effective “size” of ion
Hydration shell affects interactions with proteins
Describe membranes.
phospholipid bilayer.
amphipathic - hydrophilic polar head & hydrophobic tail.
basically impermeable to ions
Describe pumps.
primary active transport.
hydrolysis of ATP.
Live in membranes Move ions “Uphill” Couple to ATP (usually) Fairly slow Nearly always move cations e.g. Na+ / K+ ATPase
Describe secondary active transport carriers.
Couple downhill flow of ions to uphill flow of a different ion
Don’t use energy from ATP directly– energy comes from concentration gradient of downhill ions (but gradients are made by burning ATP)
Have two types: antiporters and symporters
?
Describe the sodium pump.
3 Na+ out
2 K+ in
per ATP hydrolysed.
Describe voltage gated channels.
Open in response to changes in membrane potential (voltage)
All voltage gated channels (mostly) have:
Pore - Lets ions through
Voltage Sensor -Tells channel to open in response to voltage change
Coupling mechanism - Couples channel opening to voltage sensing
Inactivation mechanisms - Close channel
4 subunits, pore in centre gate at top.
Describe ligand gated ion channels.
Open in response to binding of an activating ligand (agonist) e.g. acetylcholine
All ligand gated channels have:
Pore - Lets ions through
Ligand binding site -Tells channel to open in response to ligand binding
Coupling mechanism - Couples channel opening to ligand binding
Desensitization mechanisms - Close channel if ligand binds for too long
Describe the nicotinic ach receptor.
5 subunits.
What did Adolf Fick show about ion diffusion?
number of molecules moving across an interface is proportional to the area of the interface and the conc gradient.
what did einstein show about diffusion rate?
faster in 3 dimensions than 2 > 1.
less room to collide, compare to airport.
catalysts work by trapping molecules in 2 dimensions.
What is the electrochemical gradient?
total gradient
Gradient caused by diffusion - Gradient caused by electrophoretic movement.
What are electrophoretic movements?
The movements of ions under the influence of an electric field are called electrophoretic movements.
What determines the rate at which ions move across a membrane?
The size of the electrochemical gradient.
The nature of the ion.
Number of open ion channels.
The properties of the ion channel (selectivity/permeability)
What is a current?
flow of ions.
What is voltage?
potential difference.
difference in ion conc.
If the potential is 1 Volt, it takes 1 Joule of work to move 1 Coulomb of charge
What is Ohm’s law?
Current (I) = Volts (V)
Resistance (R)
Why are electrophysiological recordings made?
Extremely fast events – sub-millisecond timescale upwards
Extremely sensitive – as little as one ion channel can be detected
Spatial resolution – good
Dissect details of individual channels
– activation, inactivation, pore properties
Why does calcium conc have to be so low inside the cell?
signalling molecule, not a charge carrier.
our ancesters decided to use ATP - which has phosphate.
calcium phosphate is insoluble.
What charge is the inside of a cell?
negative.
To move 1 mole of z-valent ions through a membrane potential of Vm Volts takes:
Z-valence x F x voltage.
in joules
How many coulombs in 1 mole of univalent ions?
F
Faradede constant?
what is a z-valent?
charge of an ion
ie 2+ for Ca
To move 1 mole of substance from a concentration ci (inside cell) to co (outside cell) takes:
R x Temp x ln (conc inside/outside)
ln = log e
T - kelvin
R - universal gas constant. 8.314
In joules
How do you calculate the total work?
electrical gradient + conc gradient
= z.F.Vm +R.T.ln(ci/co)
Describe the outcomes of total work.
Work > 0
Energy is needed to move ion across membrane (needs active transport)
Work <0
Energy is released when ion moves across membrane (“downhill” – occurs spontaneously)
Work =0
No energy required or released i.e. at equilibrium
What is the total work when at equilibrium?
total work = 0
0 = z.F.Vm +R.T.ln(ci/co)
rearrange to get
Vm = [R.T.ln(co/ci)]/z.F
Nernst equation
what is the simpler nernst equation?
convert to log10 and assume body temperature.
Vm = [61.5 log10(co/ci)]
/z
Learn inside/out conc of ions?
?
How do Na and K move at equilibrium.
neither is at equilibrium really.
K+ -80mv
Na+ +61.5mv
What is a capacitor?
stores energy on plates that are separated by an insulator.
Hardly any ion movement is required to charge the capacitor and set up the membrane potential. Therefore, there is almost no change in ion concentration (0.006% of K+ ions leave).
mean AP don’t require lots of energy to move high vol of ions.
high voltage low current.
How does the body code for stimulus intensity?
frequency of action potentials, not size.
Learn the stages of the action potential.
resting potential depolarisation to stimulus rising phase peak falling phase undershoot/hyperpolarisation resting
-70mv resting
hyperpolarisation -80mv
-55mv threshold
at peak Na close and K open
Describe the structure of a Na+ channel.
24 membrane spanning domains, 4 pseudosubunits.
alpha forms the channel
What is the structure of a K+ channel.
Four subunits are seperate proteins.
How do Na channels open and close?
at threshold channel opens.
sodium ions come inside cell.
voltage increases.
inactivation gate plugs the channel.
How do K channels open.
Slower than Na+
no inactivation gate, it just closes.
Feedback loops in the action potential?
positive feedback of Na channels until K+ open.
Describe the refractory periods of an action potential.
during peak - absolute refractory period, no AP made.
during hyperpolarisation - relative refractory period.
less excitable, needs a larger stimulus to create AP.
Due to inactivation of Na current and turn on of K current.
Where do Action Potentials occur?
neurones and cardiac muscle. purkyrne tissue?
What are the types of transmission?
electrical - within neurones
chemical - between neurones
What does attenuated mean?
current being lost as it flows.
What part of the neurone are attenuated?
dendrites - attenuated
axon - current not attenuated
How do you measure tenuation?
V = Vo exp-x/λ
λ is the length constant
λ is when voltage drops to 37% of it’s original value.
Why does attenuation not occur in dendrites?
short distances involved. many inputs (big starting signal)
dendritic transmission is passive, no waves of action potentials.
Why do axons not suffer from attenuation?
Axons have a far higher density of sodium channels than dendrites, can generate action potentials.
myelination insulates and decreases leak.
saltatory conduction. nodes of ranvier, internodes.
what are the methods of decreasing attenuation?
better insulation
better conducting core
fatter “cable” (diameter of axon)
How does saltatory conduction occur?
any current lost in internodes is boosted back up at the next node of ranvier.
diffusion is faster than the transmission of an axon.
Describe myelination.
schwann cells in PNS
oligodendrocytes in CNS
wraps around the neuron many times.
only at axons.
Describe multiple sclerosis.
demyleinating disease of oligodendrocytes. CNS
(Guillain-Barré syndrome: autoimmune attack on myelin in the PNS).
autoimmune, attacks self.
loss of myelin sheath.
axon can’t transmit AP properly since no Na+ channels where myelination was. attenuation.
Na+/K+ ATPase
sodium pumps in AP
The mobility of an ion in water is proportional to the size of its:
hydration shell??