Neurohistology/Membrane/Synapses

Steps of synaptic transmission

1. AP reaches presynaptic terminal

2. Depolarizaiton causes opening of Ca channels

3. Ca influx, bind to synaptotagmin

4. Vesicle fuses to presynaptic membrane

5. Exocytosis of NT

6. NT diffuses across synaptic cleft

7. NT binds to postsynaptic receptor

8. Postsynaptic channels open

9. PSP occurs

10. Vesicle recycles

Identify the proteins involved in neurotransmission

3 SNARE:

• synaptobrevin

• synaptotaxin

• SNAP 25

Synaptotagmin

Function of SNARE proteins

Pulls membrane of vesicle together with presynaptic membrane

Synaptotagmin function

Complexes with calcium to catalyze membrane fusion for exocytosis to occur

Which disease is involved with Ca+ channel loss of function

Lambert-Eaton Myasthenia

Pre-Synaptic Diseases

Botulism (paralysis)

Tetanus (contraction)

Lambert-Eaton Myasethnia (muscle weakness)

What effect do botulism/tetanus toxins have

Cleave SNARE proteins (presynaptic)

Prevents vesicle fusion for exocytosis

What neurotransmitter is involved with botulism

Acetylcholine; failure of its release prevents excitation of muscle

Types of Post-synaptic receptors

Ionotropic

Metabotropic

What do the 2 types of postsnyaptic membrane receptors have in common

• both can induce PSP

• can be bound by the same NT

What determines whether a PSP is excitatory or inhibitory

The ions that flow through ionotropic receptors

Excitatory ionotropic receptors are permeable to ___

Na and K

Inhibitory ionotropic receptors are permeable to ___

Chloride

What effect does tetanus toxin have (which neurons does it impact)

Cleaves SNARE proteins
Prevents vesicle fusion and NT release
Prevents inhibitory interneurons from inhibiting motor neurons

Excitatory neurotransmitters

Acetylcholine
Glutamate

Inhibitory neurotransmitters

GABA

Glycine

What does acetylcholine target

muscle and brain

Acetylcholine receptor

Nicotinic (ionotropic)

Nicotinic receptors are permeable to ____

Na and K (excitatory)

Termination of acetylcholine

Hydrolysis to acetate and choline by acetylcholinestrase in the synaptic cleft

What happens if ACh accumulates

Nicotinic receptors become less responsive to acetylcholine binding, meaning neuromuscular paralysis

Postsynaptic disease

Myasthenia Gravis

What occurs in Myasthenia Gravis

Antibodies against acetylcholine receptors causes reduction to the excitatory PSP

What improves myasthenia gravis

Treatment with acetylcholinestrase inhibitors

What terminates glutamate action

Uptake into neurons and glia by glutamate transporters

Neurotransmitter associated with memory and learning

Glutamate

Excitotoxic neurotransmitter

glutamate

How is GABA action terminated

Uptake by neurons and glia

Which neurotransmitter are benzodiazepines, barbituates, alcohol associated with

GABA

How do benzodiazepines, barbituates, alcohol affect the NT they are associated with

They enhance the inhibitory PSP effect of GABA by increasing the frequency of chloride channels opening

Biogenic amines mainly act on ___

metabotropic receptors

Catecholamines include___

dopamine
norepinephrine
epinephrine

biogenic amines

dopamine

epinephrine

norepinephrine

serotonin

histamine

action of dopamine termination

uptake into nerve terminals or glia

What do MAO and COMT degrade

catecholamines

what is dopamine involved in

reward, motivation, motor control

disease involved with dopamine

parkinson’s (loss of dopamine production)

what is perikaryon

-cell body

-contains nucleus and organelles

CNS components

-brain

-spinal cord

-cranial and spinal nerve roots

PNS components

peripheral nerves

distal spinal nerves
ganglia

where does protein synthesis occur in neuron

cell body

dendrite

receives signals coming into the neuron

axon function

transmit electrical impulses away from the cell body

hallmark of synapses

1. presynaptic vesicles

2. postsynaptic densities

which neuron lacks an axon

retinal amacrine cell

what facilitates axonal transport

microtubules and motor proteins (kinesin and dynein)

motor protein involved with anterograde transport

kinesin

motor protein involved with retrograde transport

dynein

anterograde vs retrograde transport

anterograde can be fast or slow and uses kinesin

retrograde is only fast and uses dynein

the site where the axon makes contact with the adjacent neuron

axon terminal

key differences for glial cells

-non excitable

-mitotic

-support role

astrocytes functions

-structural support

-maintain blood brain barrier

-neurotransmitter metabolism

-maintains chemical environment around neurons

neural components/glial cells found in gray matter

-cell body

-axon

-dendrites

-astrocytes

-oligodendrocytes

-microglia

neural components/glial cells found in white matter

-axons

-oligodendrocytes

-astrocytes

-microglia

what mostly constitutes the blood brain barrier

tight junctions between endothelial cells

how do astrocytes support endothelial cells

provide structural support to endothelial cells with foot like processes

oligodendrocyte function

form a lipid rich structure surrounding axons

glucose is permeable/impermeable to BBB

permeable

lactate : permeable/impermeable to BBB?

permeable

amino acids permeable/impermeable to BBB?

permeable

ribonucleosides permeable/impermeable to BBB?

permeable

lipid soluble compounds permeable/impermeable to BBB?

permeable

DOPA permeable/impermeable to BBB?

permeable

albumin permeable/impermeable to BBB?

impermeable

antibodies permeable/impermeable to BBB?

impermeable

protein bound substances: permeable/impermeable to BBB?

impermeable

polar molecules: permeable/impermeable to BBB?

impermeable

what is the myellin sheath interrupted by

nodes of ranvier

which cells form myelin in the peripheral nervous system

Schwann cells

multiple sclerosis is associated with which glial cell

ogliodendrocytes

___ cells line the cerebral ventricles

ependymal

ependymal cell function

barrier between CSF and interstitial fluid

manage the CSF along via cillia

choroid plexus cells

produce CSF

What membrane process requires the most energy in the brain?

Restoring ion gradients via the Na/K pump

membrane potential in simple terms

the amount of extra negative or positive charge inside the cell

what creates the membrane potential

active transport pumps

ion channels

why do neurons have a negative resting potential

they are more permeable to K+, so potassium leaves and the cell becomes more negative (K+ channels are more open)

equilibrium potential for K+ channels

-90 mV

equilibrium potential for Na+ channels

+60 mV

phases of action potential and channels

resting membrane potential (K+ ion leak channels)

depolarization due to opening of Na+ voltage gated ion channels

depolarization stops, Na+ channels close and K+ channels open

repolarization starts due to opening of K+ voltage gated channels

Repolarization eventually stops when K+ voltage gated channels close

what occurs during refractory period

Na+ voltage gated channels become inactivated

K+ channels are recruited

how does the refractory period end

Na+ voltage gated channels become active again

K+ channels close

(K+ leak channels are now maintaing resting membrane potential)

Properties of action potential propagation

• unidirectional

• constant velocity

• non-decremental

what explains why action potential is unidirectional

refractory period in the backward direction along the axon

what part of the axon contains most of the voltage gated ion channels

nodes of ranvier