Neurons & Neural Transmission
The Neuron: Structure and Classification
A neuron is a specialised cell that receives, integrates, and transmits information through electrical and chemical signals. A typical neuron has three main structural parts: the soma, dendrites, and axon. Dendrites receive incoming signals, the soma supports the cell and integrates much of this input, and the axon carries signals toward other neurons, muscles, or glands. Most mature neurons are post-mitotic and do not routinely divide.
Main Parts of a Neuron
Soma (Cell Body)
Contains the nucleus, mitochondria, Nissl bodies and other organelles required for cellular metabolism and protein synthesis. It also receives and integrates many of the graded signals arriving from dendrites.
Dendrites
Branching processes specialised for receiving synaptic input. Many dendrites contain dendritic spines, small protrusions that provide sites for synaptic contact. Postsynaptic potentials in dendrites and soma are graded: their size varies with the strength and pattern of input.
Axon
A process specialised for conducting action potentials toward axon terminals. Axons vary greatly in length and may be myelinated or unmyelinated.
Axon Hillock and Initial Segment
Graded inputs are integrated near the axon hillock. Action potentials are normally initiated at the axon initial segment, which contains a high density of voltage-gated Na+ channels and has a low threshold for spike generation.
Axon Terminals
Terminal swellings contain synaptic vesicles. Arrival of an action potential opens voltage-gated Ca²⁺ channels, and Ca²⁺ entry triggers vesicle fusion and neurotransmitter release.
Myelin Sheath
A lipid-rich insulating sheath around many axons. It is formed by oligodendrocytes in the CNS and Schwann cells in the PNS and markedly increases conduction speed.
Nodes of Ranvier
Gaps between myelinated segments where voltage-gated ion channels are concentrated. In myelinated axons, the action potential is regenerated mainly at these nodes during saltatory conduction.
Functional Classification
Sensory (Afferent) Neurons
- Carry information toward the CNS
- Include somatic sensory and visceral sensory afferents
- Many primary sensory neurons are pseudounipolar
Motor (Efferent) Neurons
- Carry information away from the CNS
- Somatic motor efferents innervate skeletal muscle
- Autonomic efferents innervate smooth muscle, cardiac muscle and glands
Interneurons
- Located within the CNS
- Connect and integrate neural signals within local or distributed circuits
- Also called association neurons in older terminology
Structural Classification
Multipolar
- One axon and many dendrites arise from the soma
- Most common morphological class in the CNS
- Includes many interneurons and motor neurons
Bipolar
- One axonal process and one dendritic process arise from opposite sides of the soma
- Examples include retinal bipolar cells and olfactory receptor neurons
Pseudounipolar
- A single process leaves the soma and divides into peripheral and central branches
- Typical of primary sensory neurons in dorsal root ganglia
Glial Cells and Myelination
Neurons function within a cellular environment maintained by glial cells. Across the human brain as a whole, neuronal and non-neuronal cell numbers are in the same broad range; there is no single large fixed glia-to-neuron ratio that applies throughout the brain. Glia support neural signalling through homeostatic regulation, myelination, immune surveillance, metabolic support and regulation of the extracellular environment.
Astrocytes
Contribute to formation and maintenance of the blood-brain barrier, regulate extracellular ions such as K+, take up neurotransmitters from the extracellular space, provide metabolic support and participate in synaptic regulation.
Oligodendrocytes
Produce myelin in the CNS. A single oligodendrocyte can myelinate segments of multiple axons.
Schwann Cells
Produce myelin in the PNS. Each myelinating Schwann cell forms one myelin segment around one axon. The Schwann-cell sheath also supports peripheral axonal regeneration after some injuries.
Microglia
Resident immune cells of the CNS. They arise from an early myeloid lineage, survey neural tissue, respond to injury or infection, clear cellular debris and participate in inflammatory signalling.
Ependymal and Choroid-Plexus Cells
Ependymal cells line the brain ventricles and central canal and help circulate cerebrospinal fluid (CSF). Most CSF production occurs in the choroid plexus, whose specialised epithelium is related to ependymal cells.
Oligodendrocytes: CNS Myelin
- Located in brain and spinal cord
- One cell can myelinate segments of multiple axons
- CNS axons generally regenerate poorly after major injury
- Central demyelination is a defining feature of multiple sclerosis
Schwann Cells: PNS Myelin
- Located in peripheral nerves
- One myelinating cell forms one internodal segment
- Support regeneration of some injured peripheral axons
- Peripheral demyelination occurs in disorders such as Guillain-Barré syndrome
Resting Membrane Potential
When a neuron is not firing, its membrane potential is commonly around −70 mV, meaning that the inside is negative relative to the outside. The exact value varies by neuron. This resting membrane potential depends mainly on unequal ion distributions and selective membrane permeability, especially the high resting permeability to K+.
The membrane is a phospholipid bilayer. Ions cannot freely cross its hydrophobic interior, so their movement depends on ion channels, transporters and pumps. Two forces influence ion movement: the concentration gradient and the electrical gradient. The membrane voltage at which these forces balance for a particular ion is that ion's equilibrium potential.
Ion Distribution at Rest
| Ion | Typical Concentration Pattern | Resting Contribution |
|---|---|---|
| Potassium (K+) | Higher inside | High resting K+ permeability allows K+ to diffuse outward; this is the largest contributor to the negative resting potential |
| Sodium (Na+) | Higher outside | Resting Na+ permeability is low but not zero; inward Na+ leak slightly offsets the K+-dominated negativity |
| Chloride (Cl−) | Usually higher outside in mature neurons | Its contribution depends on Cl− transport and membrane permeability; in many neurons its equilibrium potential lies near the resting level |
| Organic anions (A−) | Trapped inside | Large negatively charged proteins and other anions cannot freely cross the membrane and contribute to intracellular negativity |
The Na+/K+ ATPase uses ATP to move 3 Na+ ions out and 2 K+ ions in per cycle. Its main role is to maintain the Na+ and K+ concentration gradients on which the resting potential and action potentials depend. Because each cycle moves one net positive charge outward, it also makes a smaller direct electrogenic contribution to the resting voltage.
Action Potential and Refractory Periods
An action potential is a rapid, regenerative change in membrane voltage that propagates along the axon. When depolarising graded potentials bring the axon initial segment to threshold, voltage-gated Na+ channels open rapidly and initiate the spike.
Membrane Voltage States
Resting
The membrane is polarised, commonly near −70 mV, with the inside negative relative to the outside.
Depolarisation
The membrane potential becomes less negative. Once threshold is reached at the initial segment, voltage-gated Na+ channels open rapidly and Na+ influx produces the rising phase.
Peak / Overshoot
The membrane becomes positive, often reaching roughly +30 to +50 mV. Around the peak, many Na+ channels are already inactivating while delayed voltage-gated K+ channels are opening.
After-Hyperpolarisation
After repolarisation, K+ conductance may remain elevated briefly, making the membrane more negative than its resting level and temporarily reducing excitability.
Once threshold is reached, an action potential proceeds with a stereotyped amplitude. Stronger sustained input does not make each action potential larger; it can increase firing frequency within the physiological limits of the neuron. The accompanying lab is an illustrative model of this rate-coding relationship rather than a universal fixed mapping from stimulus strength to firing rate.
Raise the stimulus and watch what changes about the spikes, and what never changes.
- Spike heightNo spike
- Firing rateSilent
Phases of the Action Potential
Threshold
The membrane voltage at which inward current becomes sufficient to trigger regenerative opening of voltage-gated Na+ channels. A value near −55 mV is commonly used for teaching, but threshold varies across neurons and conditions.
Depolarisation
Voltage-gated Na+ channels open rapidly. Na+ enters down its electrochemical gradient and drives the membrane potential toward positive values.
Repolarisation
Na+ channels inactivate while voltage-gated K+ channels open. K+ exits the cell and the membrane potential moves back toward negative values.
After-Hyperpolarisation
Some K+ channels remain open after the membrane has crossed its resting level, producing a temporary undershoot before resting conductances are re-established.
Refractory Periods
Absolute Refractory Period
- Begins during the action potential and extends into early repolarisation
- Many voltage-gated Na+ channels are inactivated and cannot reopen immediately
- A second action potential cannot be initiated, regardless of stimulus strength
- Its duration places an upper theoretical limit on firing frequency
Relative Refractory Period
- Follows the absolute refractory period
- Some Na+ channels have recovered while K+ conductance may remain elevated
- A stronger-than-usual depolarising input can trigger another action potential
- Excitability gradually returns toward baseline
Axonal Propagation and Saltatory Conduction
An action potential is regenerated along the axon rather than moving as a single physical object. Local current from an active membrane region depolarises the next region to threshold. In unmyelinated axons, regeneration occurs continuously along the membrane. In myelinated axons, current spreads rapidly beneath the myelin and action potentials are regenerated mainly at the nodes of Ranvier. This is saltatory conduction.
Add, remove and then damage the myelin, and watch where the spike must be rebuilt.
- Conduction speed
- 0.5–2 m/s
- Spike rebuilt
- At every point along the membrane
- Found in
- C fibres: pain and temperature
Continuous Conduction
- Occurs in unmyelinated axons
- Action potential is regenerated along successive membrane regions
- C fibres provide a common slow-conducting example at roughly 0.5–2 m/s
- Ion exchange occurs along a larger proportion of the axonal membrane
Saltatory Conduction
- Occurs in myelinated axons
- Current spreads beneath myelin and the spike is regenerated mainly at nodes of Ranvier
- Large A fibres provide a fast-conducting example at roughly 70–120 m/s
- Myelination increases both conduction speed and energetic efficiency
Loss of myelin increases current leakage and can slow or block conduction. Multiple sclerosis is an important CNS example of demyelination, but demyelination as a mechanism is not synonymous with MS and can occur in other disorders.
Synaptic Transmission
A synapse is a specialised junction through which a neuron communicates with another neuron or an effector cell. In a chemical synapse, the presynaptic terminal and postsynaptic membrane are separated by a synaptic cleft. Neurotransmitter released from the presynaptic terminal binds to receptors on the postsynaptic cell. Electrical synapses instead connect cells through gap junction channels and can transmit current directly.
Anatomy of a Chemical Synapse
Steps of Chemical Synaptic Transmission
EPSPs, IPSPs and Summation
A chemical synapse usually produces a graded postsynaptic potential. Whether the postsynaptic neuron reaches threshold depends on the combined effect of excitatory and inhibitory inputs. The direction of a transmitter's effect depends on the receptor and ion channels or signalling pathways activated, so the same chemical messenger can produce different effects at different receptors.
EPSP: Excitatory Postsynaptic Potential
- Moves the membrane potential toward spike threshold
- Often involves net inward positive current
- Increases the probability of postsynaptic firing
- Is graded rather than all-or-none
IPSP: Inhibitory Postsynaptic Potential
- Reduces the probability of reaching spike threshold
- May involve Cl− entry, K+ exit or other inhibitory conductances
- Can hyperpolarise the membrane or stabilise it below threshold
- Is graded rather than all-or-none
Temporal summation occurs when postsynaptic potentials from the same input arrive close together in time and overlap. Spatial summation occurs when potentials from different synapses overlap. Their combined influence is integrated across the dendrites, soma and axon initial segment.
Neurotransmitter Clearance
Reuptake
Transporter proteins remove transmitter from the extracellular space. Depending on the transmitter, uptake may occur into the presynaptic terminal, surrounding glial cells, or both. Reuptake inhibitors prolong extracellular transmitter availability.
Enzymatic Degradation
Enzymes break down transmitter molecules. A classic example is acetylcholinesterase, which rapidly hydrolyses acetylcholine at cholinergic synapses.
Diffusion
Transmitter molecules can diffuse away from the synaptic cleft and become diluted or taken up elsewhere.
Neurotransmitters and Receptors
A neurotransmitter is a chemical messenger released by a neuron that acts on receptors of another cell. Receptor binding is selective, but neurotransmitter action is not determined by the transmitter alone. The same transmitter can be excitatory, inhibitory or modulatory depending on the receptor subtype, cell and signalling pathway involved.
Major Chemical Groups
| Group | Examples | General Features |
|---|---|---|
| Amino acids | Glutamate, GABA, glycine | Prominent fast transmitters in the CNS; include both excitatory and inhibitory signalling |
| Monoamines | Dopamine, norepinephrine, serotonin | Often arise from relatively small nuclei with widespread projections and commonly have modulatory effects |
| Acetylcholine | Acetylcholine (ACh) | Acts through nicotinic and muscarinic receptors; important in neuromuscular, autonomic and CNS signalling |
| Neuropeptides | Endorphins, enkephalins, Substance P, oxytocin | Often slower and longer-lasting; may be co-released with small-molecule transmitters |
| Purines | ATP, adenosine | Participate in neural and glial signalling; adenosine commonly has inhibitory/modulatory effects |
Ionotropic and Metabotropic Receptors
| Ionotropic Receptors | Metabotropic Receptors |
|---|---|
| Receptor is directly linked to an ion channel | Receptor acts through G proteins and intracellular second-messenger pathways |
| Usually produces rapid, relatively brief effects | Usually produces slower, more prolonged or modulatory effects |
| Examples: nicotinic ACh, AMPA, NMDA, GABA-A | Examples: muscarinic ACh, dopamine receptors, most serotonin receptors, GABA-B |
Major Neurotransmitters: Functions and Principal Sources
| Neurotransmitter | Principal Sources / Distribution | Main Functions and Associations |
|---|---|---|
| Glutamate | Widely distributed; prominent in cortical and hippocampal projection neurons | Main excitatory transmitter in the CNS; central to many forms of synaptic plasticity; excessive activation can contribute to excitotoxicity |
| GABA | Widely distributed inhibitory interneurons and projection systems | Main inhibitory transmitter in the mature CNS; GABA-A and GABA-B receptors use different mechanisms |
| Glycine | Especially spinal cord and brainstem | Major inhibitory transmitter in spinal and brainstem circuits |
| Acetylcholine (ACh) | Basal forebrain and brainstem cholinergic nuclei; also peripheral motor and autonomic synapses | Attention, arousal, memory and neuromuscular/autonomic transmission; degeneration of basal-forebrain cholinergic neurons occurs in Alzheimer's disease |
| Dopamine (DA) | Substantia nigra, ventral tegmental area and hypothalamic systems | Movement, reinforcement, motivation and cognition; nigrostriatal dopamine loss is central to Parkinson's disease, while altered dopaminergic signalling is implicated in psychosis |
| Serotonin (5-HT) | Raphe nuclei with widespread projections | Modulates mood, sleep, appetite, pain and other functions through multiple receptor families; psychiatric disorders cannot be reduced to a simple “low serotonin” model |
| Norepinephrine (NE) | Locus coeruleus and related brainstem groups | Arousal, vigilance, attention and stress-related modulation |
| Endorphins / Enkephalins | Distributed peptide systems | Endogenous opioid signalling involved in pain modulation, reward and stress responses |
Co-Transmission
Many neurons release more than one chemical messenger. A neuron may co-release two classical transmitters or a fast small-molecule transmitter together with a neuropeptide. The older interpretation of Dale's principle as “one neuron releases only one neurotransmitter” is therefore too restrictive. A more useful modern formulation is that a neuron has a characteristic set of transmitters that can be released from its terminals under appropriate conditions.
Synaptic Plasticity
Synaptic plasticity is a lasting change in the efficacy of synaptic transmission produced by neural activity. It is an important cellular mechanism through which experience can alter neural circuits. Two major forms are long-term potentiation (LTP), a persistent strengthening of synaptic efficacy, and long-term depression (LTD), a persistent weakening.
Long-Term Potentiation
A widely studied form of hippocampal LTP occurs at glutamatergic synapses. Glutamate first activates AMPA receptors and depolarises the postsynaptic membrane. With sufficient depolarisation, the Mg²⁺ block of NMDA-receptor channels is relieved. NMDA receptors then permit Ca²⁺ entry, activating intracellular signalling pathways that strengthen transmission, including increased AMPA-receptor function and insertion into the postsynaptic membrane. After potentiation, the same presynaptic input can produce a larger postsynaptic response.
Hebbian Plasticity
Hebb proposed that repeated co-activation of connected neurons can strengthen their functional connection. The phrase “neurons that fire together, wire together” is a later summary of this principle. Some forms of LTP show properties consistent with Hebbian learning.
Long-Term Potentiation (LTP)
A persistent increase in synaptic efficacy after particular patterns of activity. High-frequency stimulation is a classic experimental induction method, but LTP is defined by the lasting increase in synaptic strength rather than by one universal stimulation protocol.
Long-Term Depression (LTD)
A persistent decrease in synaptic efficacy. Lower-frequency stimulation can induce LTD in some well-studied preparations, but induction conditions and mechanisms vary across synapses and brain regions.
Kandel's Aplysia Research
Eric Kandel and colleagues used the sea slug Aplysia because its large, identifiable neurons allowed behavioural learning to be connected with measurable synaptic changes. In the gill-withdrawal circuit, habituation is associated with reduced transmitter release from sensory-neuron terminals, whereas sensitisation involves facilitatory modulation that increases transmitter release. These findings helped establish synaptic plasticity as a cellular mechanism through which learning can alter neural circuits.
General definitions and behavioural applications of habituation and sensitisation belong primarily to the Learning notes. Here, their importance is the demonstration that experience can produce identifiable changes in synaptic transmission.
Cortical spreading depression is a slowly propagating wave of intense depolarisation followed by prolonged suppression of neural activity. It has been induced experimentally, including with high extracellular K+, and was used in older memory-consolidation research as a temporary neural-disruption method. It is distinct from LTP and LTD and is retained here only for recognition-level exam coverage.
Previous Year Questions
Match the following:
- a.-67 mv
- b.+45 mv
- c.-70 mv
- d.-72 mv
- i)Polarized
- ii)Hyperpolarized
- iii)Depolarized
- iv)Completely depolarized
Rapid Revision and Researcher Reference
Researcher Reference
| Researcher | Year | Contribution | Associated Term |
|---|---|---|---|
| Santiago Ramón y Cajal | 1890s | Established the neuron doctrine and described neural cellular organisation | Neuron doctrine; dendritic spines; neural circuits |
| Charles Sherrington | 1897 | Introduced the term “synapse” and developed principles of neural integration | Synapse; summation; reciprocal innervation |
| Otto Loewi | 1921 | Demonstrated chemical transmission from the vagus nerve to the heart | Vagusstoff; chemical neurotransmission |
| Donald Hebb | 1949 | Proposed activity-dependent strengthening of connections between co-active neurons | Hebbian learning; Hebb synapse |
| Alan Hodgkin & Andrew Huxley | 1952 | Described the ionic conductances underlying the action potential | Voltage clamp; Na+/K+ conductance; Hodgkin-Huxley model |
| Henry Dale | Early 20th century | Major work on acetylcholine and chemical transmission; later interpretations of “one neuron = one transmitter” proved too restrictive | Acetylcholine; Dale's principle; co-transmission qualification |
| Bliss & Lømo | 1973 | Described long-term potentiation in hippocampal pathways | LTP; enduring synaptic strengthening |
| Eric Kandel and colleagues | 1960s–2000 | Linked simple forms of learning in Aplysia to identifiable changes in synaptic transmission | Habituation; sensitisation; synaptic plasticity |