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basic neuroscience

mini BrainCamp 2020-04-27

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what is a neuron?

the fundamental unit of the nervous system

soma / cell body

signal integration

axon

signal conduction

synapses

signal transmission

dendrites

signal reception & integration

Here shown is a typical ‘textbook’ neuron. Most neurons look quite different, but this is a good way of visually depicting the various compartments.

In many ways, neurons are like any other cell in your body. They have a nucleus, mitochondria, cytoskeleton – all the organelles necessary for cellular metabolism. However, neurons also have multiple specialisations – several compartments with distinct functions.

Soma (cell body) contains the nucleus. Protruding from the soma are branching processes called dendrites. Their function is reception of signals from other neurons, and integration of those signals.

A different type of protrusion is the axon. Every neuron has exactly one axon, although it can be branched. It is responsible for signal conduction, sometimes over large distances – connecting two brain areas or, like the sciatic nerve, your spinal cord to your toe.

At the ends of the axon, there are axon terminals that form contacts with the dendrites of other neurons. These contacts are called synapses, and their function is signal transmission from one neuron to the next.

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how do neurons communicate?

voltage is the currency of neuronal communication

synaptic potentials in dendrites / soma:

small, proportional to input strength,

can be positive or negative

axon hillock

action potential initiation

action potentials in axon*:

large, ‘all-or-nothing’

*can also backpropagate into dendrites

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membrane potential

there is an electrochemical gradient across the neuronal membrane

selectively permeable membrane

energy-dependent Na⁺ / K⁺ pump (3 Na⁺ out, 2 K⁺ in per 1 ATP)

high Na⁺

high Cl^–

low K⁺

low Na⁺

low Cl^–

high K⁺

Δ = 65 mV

Na⁺ channel

K⁺ channel

Na⁺ / K⁺ pump

+ lots of negatively charged macromolecules

neurons have a resting membrane potential of –65 mV

at rest, membrane is mostly permeable to K⁺

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membrane potential

extra

V_X is the membrane potential at which there would be no net flow of ion X if it could cross the membrane freely

X

intracellular concentration of X

extracellular concentration of X

Faraday’s constant�~96500 C/mol

valence of X

equilibrium potential

temperature [in K]

gas constant�8.314 J/K.mol

the resting membrane potential is close to the K⁺ equilibrium potential

(–90 mV)

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recap I

neurons are composed of dendrites, soma, and a single axon

neurons contact each other at synapses

neurons communicate with voltage: synaptic and action potentials

neuronal membrane contains ion channels & Na⁺ / K⁺ pumps

membrane potential at rest is approximately –65 mV

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action potentials

neurons are excitable cells

threshold

–50 mV

resting Vm

–65 mV

refractory period

voltage-gated Na⁺ channels open

if membrane potential ≥ threshold:

hyperpolarisation

Na⁺ flows into the cell

vg Na⁺ channels inactivate

depolarisation

vg K⁺ channels open

K⁺ flows out of the cell

K⁺ keeps flowing out

repolarisation

hyperpolarisation

absolute refractory period

vg Na⁺ channels de-inactivate

vg K⁺ channels close

return to resting potential

relative refractory period

peak

+30 mV

depolarisation

repolarisation

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recap II

neurons communicate using ‘all-or-nothing’ action potentials

action potentials make neurons excitable

actions potentials are mediated by voltage-gated Na⁺ & K⁺ channels

action potentials have a refractory period

refractory period:

prevents depolarisation block

limits action potential frequency

ensures unidirectional propagation

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dendrites

a major determinant of single neuron computational power

dendritic spines

signal reception

often highly branched

morphologically diverse

large surface area

compartmentalised

can do logical operations

depends on the distance to soma & local mechanisms

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axons

propagate action potentials over potentially long distances

myelin

insulation

nodes of Ranvier

action potential regeneration

(e.g. sciatic nerve from spine to toe)

speed increases with axon ⍉ and myelination

nodes of Ranvier have high density of ion channels and pumps

propagation speed ranges 1-100 m/s

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the synapse

voltage-gated Ca²⁺ channels

synapse

axon terminal

postsynaptic cell

synaptic vesicle

with neurotransmitter

postsynaptic receptor

mitochondria

electromicrograph

synapses are only 20-40 nm wide!

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synaptic transmission

voltage-gated Ca²⁺ channels

synapse

axon terminal

postsynaptic cell

synaptic vesicle

with neurotransmitter

postsynaptic receptor

mitochondria

action potential depolarises the terminal

voltage-gated Ca²⁺ channels open

Ca²⁺ flows into the cell

Ca²⁺ triggers synaptic vesicle fusion w/ membrane

neurotransmitter is released into the synaptic cleft

neurotransmitter binds a postsynaptic receptor

receptor activation generates a synaptic potential

or modulates the cell’s excitability / metabolism

most cells contain only

one type of neurotransmitter

(and maybe neuropeptides)

neurotransmitter is broken down or reuptaken

excess presynaptic membrane is recycled

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neurotransmitters & receptors

the main excitatory neurotransmitter is glutamate

the main inhibitory neurotransmitter in the brain is GABA

γ (gamma)

amino butyric

acid

the effect of a neurotransmitter depends on the receptor!

other chemical messengers: acetylcholine, noradrenaline, dopamine, serotonin

the main inhibitory neurotransmitter in the spinal cord is glycine

ionotropic receptor

allows ion flow,

millisecond timescale;

excitation / inhibition

neurotransmitter-receptor interactions are highly specific: lock-and-key

these molecular pathways can be hijacked by drugs & medicines

metabotropic receptor

activates 2nd messengers,

second timescale,

modulation

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neurotransmitters & receptors

glutamate	ionotropic (Na⁺, Ca²⁺)	excitation
glutamate	metabotropic	variable
GABA	ionotropic (Cl–)	inhibition
GABA	metabotropic	suppression
glycine	ionotropic (Cl–)	inhibition
acetylcholine	ionotropic (Na⁺, K⁺)	excitation
acetylcholine	metabotropic	stimulation
dopamine	metabotropic	variable
serotonin	ionotropic (Na⁺, K⁺)	excitation
serotonin	metabotropic	variable
noradrenaline	metabotropic	variable

the ultimate effect of a neuron depends on its wider network

disinhibition: inhibiting an inhibitory neuron results in excitation

feedback: activity is self-limiting

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recap III

synaptic transmission requires release of neurotransmitter

the main excitatory neurotransmitter is glutamate

the main inhibitory neurotransmitters are GABA & glycine

the effect of a neurotransmitter depends on its receptor

receptors can be ionotropic & metabotropic

the effect of a neuron depends on its wider neural network

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Cell types