- thin = hard to flow through - how easy it is for ions to flow through Ra = resistance of the axon

- autoimmune disorder where virus with an antigen that looks like myelin gets degraded as well - Epstein-Barr virus - myelin attacked/degraded by immune system - slow action potentials - also forms sclerosis scar tissue which slows a.p.s - lose feeling then it comes back - nervous system fights back to repair glial cells/myelin - first symptoms vision, tactile, balance, speech - 20-40 years old - 2x prevalence in women - genetic factors (twin studies) 1/1000 ppl

Lecture 3 + Assignment 3 Flashcards by Sophie Cournoyer

A.P. speed compared to electricity

electricity = 1/2 speed of light
A.P. speed slower

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Leaky, sticky, and thin

all make a.p.s move slower

Leaky = low membrane resistance
Rm

Sticky = high membrane capacitance
Cm

Thin = high axial resistance
Ra

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Membrane resistance / Rm

leakiness
like a balloon with a hole

Rm = resistance of the membrane

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Membrane capacitance / Cm

stickiness
ability of membrane to store charge
if it can’t store charge well, sticks to ions on the outside due to attraction
makes them travel slower

Cm = capacitance of the membrane

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Axial resistance /Ra

thin = hard to flow through
how easy it is for ions to flow through

Ra = resistance of the axon

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Invertebrates avoiding leaky/sticky/thin

evolved wider axons
they take up more space

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Vertebrates avoiding leaky/sticky/thin

myelin
- reduces axon leakiness and stickiness

saltatory conduction
- jumping between nodes of Ranvier
- makes conductance speed faster

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Myelin in CNS vs. PNS

+ Nervous system path

Oligodendrocytes
- in CNS
- connect to multiple axons

Schwann cells
- in PNS
- connect to one axon

myelin -> glial cells -> oli -> multiple axons

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Theodor Schwann

Discovered schwann cells

supported cell theory
“all living things are composed of cells and cell products”

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Multiple sclerosis

autoimmune disorder where virus with an antigen that looks like myelin gets degraded as well
Epstein-Barr virus
myelin attacked/degraded by immune system
slow action potentials
also forms sclerosis scar tissue which slows a.p.s
lose feeling then it comes back
nervous system fights back to repair glial cells/myelin
first symptoms vision, tactile, balance, speech
20-40 years old
2x prevalence in women
genetic factors (twin studies)

1/1000 ppl

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Guillain-Barre syndrome

similar to MS but in PNS
antibodies attack myelin schwann cells

1/100 000 ppl

symptoms: paresthesia, paralysis, loss of sensation
movement difficulty starting in the legs moving up
rapid onset, recovery after weeks or years

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Neuron doctrine vs. reticular theory

Golgi
- reticular theory
- neurons all connected through giant network

Santiago Ramon y Cajal
- neuron doctrine
- separate by nearby neurons

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Synaptic cleft

20-40 nm wide

beneath the resolution of conventional light microscopy

1nm = 10^-9 m

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Otto Loewi - heart in a jar

do heartbeat in one jar
slow heartbeat
makes heart in other jar also slow down
indicates chemical transmission through synapses

bc vagus nerve releases something into the saline fluid

did this experiment
used frog hearts
dreamt it up then scribbled it down but couldn’t read the stuff

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Evidence of quantal transmission

smallest possible depolarization of 0.4 mV
quantal packages during synaptic release

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Bernard Katz

found evidence of quantal transmission
1911-2003

Resting synapse

neurotransmitters in synaptic vesicles
presynaptic axon connects to postsynaptic dendrite

axon terminal = synaptic bouton

voltage-gated calcium ion channel closed

Active synapse

neurotransmitters in vesicles leave the cell (exocytosis)

bind to ligands

opens ligand-gated ion channels when they bind

opens voltage-gated calcium ion channels
Ca goes OUT

Calcium leaving the axon terminal

Ca pump lets it out of the cell as 2H enters
- uses ATP hydrolysis

Na/Ca exchanges one for another

Mechanisms of transmitter exocytosis

vesicle docks
SNARE complexes form to pull membranes together - vesicle to axon terminal membrane
exiting Ca binds to synaptotagmin on vesicle
Ca-bound synaptotagmin catalyzes membrane fusion and teurotransmitter releae

Gruber prize in neuroscience - 2012

+ how many neurotransmitters discovered

Lily Jan and Yuh Nung Jan

discovered that peptides can be neurotransmitters

over 100 neurotransmitters discovered

Small molecule amino acid neurotransmitters

Glutamate
- most common excitatory nt

GABA
- most common inhibitory nt in cerebral cortex

Glycine
- common inhibitory nt in brainstem/spinal cord

Glutamate receptor channel

glutamate binds
channel opens and lets Na in

= excitatory

has same permeability of K out as Na in (g=g)

Na has a larger driving force in so net current inward = negative current

GABA receptor channel

GABA binds
channel opens and lets Cl in
selectively permeable to Cl

= inhibitory

Driving force equation

I = g(Vm - E) I = current of ion g = membrane conductance Vm = membrane potential E = equilibrium potential Vm - E = driving force on ion

+/- Current

(+) current = outward (+) - cell loses (+) charge or gains (-) charge GETTING MORE (-) (-) current = inward (+) - cell loses (-) charge or gains (+) charge GETTING MORE (+)

Axon hillock

where axon attaches to the cell body

EPSP

- glutamatergic - depolarization

IPSP

- GABAergic - hyperpolarizaion

Spatial integration of EPSPs

lambda = length constant = √rm/ra Vx = Voe^-(x/lambda) Vx = membrane potential x = distance

Temporal integration of EPSPs

tau = time constant = rmxcm Vt = Voe^-(t/tau) Vt = membrane potential t = time

Spatiotemporal integration

- spatial and temporal EPSPs

Patch clamp - nobel prize

Nobel prize in physiology or medicine - 1991 Neher and Sakmann - invented patch clamp - discovered opening and closing of single ion channels

Patch clamp - technique

- pipette over ion channel - suction doesn't allow other ions to enter Cell-attached recordings - just take recordings with suctioned separate environment =microscopic currents - reveals characteristics of different channels Whole-cell recordings - strong pulse of suction to make cytoplasm continuous with pipette (breaks membrane) Inside-out - take a chunk and membrane closes behind it - cytoplasm facing out - can change medium inside cell Outside-out - take a chunk and membrane closes behind it - rips twice and folds back together in pipette - membrane facing out

Fast vs. slow axonal transport rates

Fast axonal transport occurs at a rate of up to 400 mm/day. - uses molecular motors like kinesin, dynein Slow axonal transport occurs at a rate of 0.5–5.0 mm/day.

Anterograde vs. retrograde transport directions

Anterograde axonal transport towards axon terminal. Retrograde axonal transport towards cell body.

Glutamate = not axonal transport

- synthesized in presynaptic cytoplasm - packaged into synaptic vesicles by vesicular glutamate transporters, aka VGLUTs - vesicles are then transported into cells by excitatory amino acid transporters, aka EAATs