graduate seminar, njit june 14, 2012 analytical & computational neuroscience: lecture 2 action...

Graduate Seminar, NJIT • June 14, 2012

Analytical & Computational Neuroscience: Lecture 2

Action Potentials and Chemical Synapses

Math 430 * Math 635 * Fall 2015 * Victor Matveev


Neuron is charged: VinVout ≈ 70mV

Outside: high Na+, low K+

Inside: low Na+, high K+

Neurons and synapses

Human brain:

~1011 neurons

~1015 synapses

Node of Ranvier


Synapses are connections between two neurons

Structure of neuron in more detail

Neuron is charged: VinVout ≈ 70mV

Outside: high Na+, low K+

Inside: low Na+, high K+

Human brain:

~1011 neurons

~1015 synapses


Myelin Sheath and Nodes of Ranvier

• Schwann cells (peripheral NS) similar to Oligodendrocytes (CNS)

• Myelinated axonal segments:

Electric potential propagates passively and fast

• Nodes of Ranvier

Action potential initiated at first node of Ranvier, and is

amplified at other nodes by voltage-dependent ion channels


gNa gK gL

VNa VK VL

Cm

Vm

Action potential (spike)Excitable cells: neurons, endocrine cells, muscle cells

Low K+

Moderate Ca2+ High Na+

Equivalent RC circuit

Vm(t )

Vrest=-75 mV

Applied current

gCa gNa

gK

(A) Vm increases

(B) Na+ channels open

(C) K+ channel open

AP time course

Vm

High K+

Very low Ca2+

Low Na+

Cell Blood

Molec Cell Biol (2000) 4th Ed. Lodish, Berk, Zipursky et al

Units: mM


gNa gK gL

VNa VK VL

Cm

Vm

Equivalent RC circuit

Vm(t )

Vrest=-75 mV

Applied current

gCa

gNa

gK

(A) Vm increases

(B) Na+ channels open

(C) K+ channel open

(D) Na+ channels close

(E) K+ channels close

AP time course

A

B

C D

E

Action potential (spike)Excitable cells: neurons, endocrine cells, muscle cells

Vm

High K+

Very low Ca2+

Low Na+

Low K+

Moderate Ca2+ High Na+

Cell Blood

Molec Cell Biol (2000) 4th Ed. Lodish, Berk, Zipursky et al

Units: mM


Chemical Synaptic Transmission

Neurotransmitter-filled vesicles

Presynapticcell (axon)

Ca2+ ions

~40nm

Postsynaptic cell (neuron or

muscle)

Neurotransmitters: glutamate, GABA, acetylcholine, serotonin, dopamine…



Action potential (depolarizing pulse)

Ca2+ ionsCa2+ channelsopen

Neurotransmitter-filled vesicles



muscle)

Neurotransmitters: glutamate, GABA, acetylcholine, serotonin, dopamine…

~40nm



Ca2+ channelsopen

Several Ca2+ ions bound to release site


Action potential (depolarizing pulse)


muscle)

~40nm



Exocytosis (fusion)

Neurotransmitter receptors/channels

Neurotransmitter diffuses into synaptic cleft



muscle)

~40nm

Vesicle fusion initiated by SNARE protein complex interacting with Ca2+-sensor synaptotagmin



Neurotranmitter binds to postsynaptic receptors




muscle)

~40nm



Postsynaptic ion channels open




muscle)

~40nm



Postsynaptic ion channels open

Influx of Na+ & Ca2+ (excitation)

K+ efflux, Cl- influx (inhibition)



muscle)

~40nm

Total transmission

delay ~ 200 μs


Synapses and Neurotransmitters (NT)

• In mammalian brain: roughly 104 synapses per neuron: 1015 total

• A given neuron secretes a single NT (single type on NT load), e.g.:

Dopaminergic neuron: synapses release dopamine

Cholinergic neuron: synapses release acetylcholine

…Etc.

• A given neuron may be activated by many NTs

Afferents (inputs): multiple NTs

Efferent (output): single NT (…well, for the most part)


Synapses and Neurotransmitters (NTs)

• Gap junctions: direct “pore”; no NT needed!

• Chemical:

○ Ionotropic (fast): receptors activate ion channels

○ Metabotropic (slow): receptors activate second messengers

• Depending on NT, chemical synapses may be

○ Excitatory

- Examples (ionotropic): glutamatergic, cholinergic

- Postsynaptic channels permeable to Na+ and Ca++

○ Inhibitory

- Examples (ionotropic): GABAergic

- Postsynaptic channels permeable to K+ and Cl-

Note: chemical synapses allow inhibitory interaction between neurons!


“Excitable” Cells

Neurons are not the only cells that change Vm

• Endocrine cells

Hormone similar to neurotransmitter

• Muscle Cells

Ca2+ important for AP and muscle contraction

graduate seminar, njit june 14, 2012 analytical & computational neuroscience: lecture 2 action...

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