AEB - Physiology

Dendrites

processes extending from the soma that receive synaptic inputs from axon terminals.

Soma

cell body containing the nucleus, responsible for integrating synaptic inputs together, and acts as the site for metabolic and genetic processes.

Axon hillock (initial segment)

specialised soma region connecting to the axon where the action potential is initiated.

Axon

fibre that conducts the action potential to the nerve terminal end. May be myelinated.

Axon terminal

site where electrical signal is converted to a chemical signal at the synapse and communicated to other nerve cells.

Back propagation

action potential initiated at the axon hillock/initial segment can travel backwards from the axon into the dendrites and soma to modulate synaptic plasticity.

Neural circuits

collections of interconnected neurons with specific inputs and outputs.

Local neural circuits

circuits communicating across one brain region, e.g. within hippocampus.

Projecting neural circuits

circuits communicating across different brain regions, e.g. thalamo-cortico circuits.

Trisynaptic hippocampal circuit

local, three-step neural pathway receiving input and producing outputs from/to entorhinal cortex and other regions for learning and episodic memory.

Neuronal excitability

ease at which nerve cells OR neuronal circuits fire action potentials.

Decreased excitability

death of excitatory neurons means action potentials are more difficult to generate or occur at lower frequencies preventing/reducing response.

Increased excitability

death of inhibitory neurons means action potentials are easier to generate or occur at higher frequencies leading to excessive responses.

Ependymal cells

epithelial cells that line the brain ventricles and central canal producing and regulating cerebrospinal fluid.

Oligodendrocytes

cells providing myelination to multiple central axons, as well as metabolic and trophic support.

Astrocytes

cells maintaining homeostasis of 100s of neurons via ion, neurostransmitter, water, metabolite, and synapse regulation, forming the blood brain barrier.

Microglial cells

immune cells of the CNS, also responsible for sculpting neural circuits, and cellular debris and synapse elimination.

Neurodegenerative pathway

pro-inflammatory microglia activate neurotoxic astrocytes which release pro-inflammatory mediators to fight infection/inflammation and clear dead cells.

Neuroprotective pathway

anti-inflammatory microglia activate glial scar forming astrocytes and neuroprotective astrocytes releasing anti-inflammatory and neuroprotective factors to aid in repair following injury.

Selective membrane permeability

membrane allows some ions to cross more easily than others occurring due to open or closure of different ion channels.

Electrochemical gradient

combination of forces action on an ion; movement down the concentration gradient (chemical) and movement toward the opposite charge (electrical).

Resting membrane potential (RMP)

voltage difference across the membrane at rest; inside of neuron is negative relative to outside (~−70 mV).

Equilibrium potential

membrane voltage where electrical and chemical forces on an ion are equal and opposite → no net movement of that ion.

Equilibrium potential for one ion

What does the Nernst equation calculate?

Rapid Na influx

Describe ion flux in depolarisation.

Na channels open

Describe permeability changes in depolarisation.

Na channel inactivate, K channels open

Describe permeability changes in repolarisation.

K efflux

Describe ion flux in repolarisation.

Slow K efflux

Describe ion flux in resting state.

Excitatory input

ion movement depolarises membrane, bring it closer to the threshold and thus increasing likelihood of an action potential.

Inhibitory input

ion movement hyperpolarises membrane, bring it further to the threshold and thus decreasing likelihood of an action potential.

Excitation due to Na influx

Reduces Na⁺ driving force inward = less Na⁺ influx in depolarisation phase.

Excitation due to Ca influx

Ca²⁺ influx depolarises cell due to very positive equilibrium potential

Inhibition due to K+ efflux

↑ K⁺ chemical gradient → more K⁺ efflux → hyperpolarisation

Inhibition due to Cl influx

Cl⁻ negative charge hyperpolarises membrane potential

Ion homeostasis

maintaining relatively stable intracellular and extracellular ion concentrations, especially K⁺ due to high resting membrane permeability.

Na⁺/K⁺ ATPase

maintains the concentration gradients by pumping 3 Na⁺ out + 2 K⁺ in using ATP.

Spatial buffering

astrocytes are high permeable K⁺, allowing K⁺ to be redistributed from active neural areas (where extracellular K⁺ is higher), to quiescent areas.

Blood brain barrier

protects the brain from dietary/peripheral fluxes in K⁺.

Hyperkalaemia

increased extracellular K⁺ from blood creates persistent depolarisation leading to. muscle twitching and irregular cardiac rhythms.

Ischaemia

ATP depletion stops active K⁺ influx causing depolarisation and an initial increase in neuronal excitability.

Excitotoxicity

excessive neuronal stimulation and intracellular Ca²⁺ → enzyme activation, mitochondrial damage and potentially neuronal death.

1 Action potential

action potential arrives at the presynaptic axon terminal.

2 Ca²⁺ channels open

action potential triggers voltage-gated Ca²⁺ channels to open, allowing to Ca²⁺ enter the presynaptic terminal.

3 Vesicle release

Ca²⁺ triggers synaptic vesicle fusion with the presynaptic membrane and neurotransmitters are released into the synaptic cleft by exocytosis

4 Neurotransmitter binding

neurotransmitters bind to receptors on postsynaptic membrane.

5 Postsynaptic pathways

binding triggers ion channels/signalling pathways, producing postsynaptic potential

Excitatory postsynaptic potential (EPSP)

neurotransmitter binding opens ion channels causing net positive charge to enter the neuron → membrane depolarises, increasing likelihood of an action potential.

Inhibitory postsynaptic potential (IPSP)

neurotransmitter binding opens ion channels causing net negative charge to enter neuron → membrane hyperpolarises, decreasing likelihood of an action potential.

AMPA glutamate receptor

glutamate binding rapidly allows mainly Na⁺ influx (and K⁺ efflux), causing rapid depolarisation and an EPSP for fast excitatory transmission.

NMDA glutamate receptor

channel blocked by Mg²⁺ at rest, but depolarisation with glutamate binding allows Na⁺ and Ca²⁺ influx (and K⁺ efflux) when activated for slower excitation and synaptic plasticity/learning and memory.

1 Impaired blood flow

in stroke supply of oxygen and glucose in blood is impaired.

2 Energy depletion

neurons cannot generate sufficient ATP to maintain ion homeostasis with Na⁺/K⁺/ATPase.

3 Membrane depolarisation

increasing extracellular K⁺ causes K⁺ efflux along its chemical gradient, raising the resting membrane potential.

4 Release of Ca²⁺

depolarisation opens voltage-gated Ca²⁺ channels, allowing Ca²⁺ to enter presynaptic terminals.

5 Glutamate release

Ca²⁺ influx triggers glutamate release, acting to depolarise the postsynaptic neuron.

6 Excitotoxic cycle

postsynaptic depolarisation triggers Ca²⁺ release again, creating further, excessive excitation that can damage neurons.

GABA or Glycine receptor

neurotransmitter binding allows mainly anion influx , causing hyperpolarisation and an IPSP.

Hyperpolarising inhibition

an inhibitory postsynaptic potential (IPSP) that makes the membrane potential more negative, moving it further from the action potential threshold, e.g. by Cl⁻ influx or K⁺ efflux.

Shunting inhibition

inhibitory Cl⁻ channels open to partially divert the incoming excitatory postsynaptic potential causing smaller depolarisation to reach axon initial segment → less likely to reach threshold.

Synaptic integration

multiple synaptic potentials are summed within one postsynaptic neuron allowing neurons to compute thousands of synaptic inputs.

Spatial summation

simultaneous addition of EPSPs from multiple synapses at different locations on a neuron.

Temporal summation

addition of multiple EPSPs from the same synapse occurring rapidly one after another at the same location.

Axodendritic

axon terminal synapses onto dendrite (typically spines), usually receiving incoming excitatory signals.

Axosomatic

axon terminal synapses onto soma, with strong influence over whether the neuron reaches threshold so can be inhibitory or excitatory.

Axoaxonic

axon terminal synapses onto another axon to modulates neurotransmitter release, often causing presynaptic inhibition.