Neurons & Neural Transmission
1.1 The Neuron
A neuron is a specialized cell that receives, integrates, and transmits information using electrical and chemical signals. It consists of a cell body (soma), branching input fibers (dendrites), and a single output fiber (axon) that transmits signals to other neurons, muscles, or glands. The human brain contains roughly 86 billion neurons, and each one may connect with thousands of others. Unlike most body cells, mature neurons do not divide.
Neurons are classified in two main ways: by their structure and by their function.
Functional Classification
Sensory (Afferent)
- Carry signals toward the CNS
- From receptors in skin, eyes, ears
- "Afferent = arriving"
- Mostly unipolar in structure
Motor (Efferent)
- Carry signals away from the CNS
- To muscles and glands
- "Efferent = exiting"
- Typically multipolar
Interneurons
- Located entirely within CNS
- Integrate sensory and motor signals
- ~99% of all brain neurons
- Also called association neurons
Structural Classification
Multipolar
- One axon + many dendrites from soma
- Most common type
- Most brain and spinal cord neurons; motor neurons
Bipolar
- One axon + one dendrite on opposite sides
- Retinal photoreceptors; olfactory neurons
Unipolar (Pseudounipolar)
- Single process divides into two branches
- Sensory neurons in dorsal root ganglia
- Most common sensory type
1.2 Structure of the Neuron
Every neuron has the same fundamental architecture: a central processing region (the soma), input branches (dendrites), and a single output cable (the axon). The soma integrates all the electrical signals arriving from dendrites and decides whether to fire. The axon carries the output signal, sometimes over a meter long in motor neurons, to the next cell in the chain.
Soma (Cell Body)
Contains the nucleus, Nissl bodies (rough endoplasmic reticulum for protein synthesis), mitochondria, and other organelles. Integrates all incoming signals. Adult neurons rely heavily on glucose as their primary energy source: unlike most body cells, they cannot effectively utilise fatty acids, making them uniquely vulnerable to hypoglycaemia.
Dendrites
Branching extensions that receive incoming signals from other neurons. Each dendrite is studded with dendritic spines, tiny protrusions that increase the surface area available for synaptic contacts. Signals arriving here are graded potentials: stronger stimuli produce larger potentials.
Axon
The single output fiber that conducts the action potential away from the soma toward the axon terminals. Covered by the myelin sheath with interruptions called nodes of Ranvier. Can range from 0.1 mm to over 1 meter in length.
Axon Hillock
The cone-shaped junction between soma and axon. This is where the neuron makes its fire/no-fire decision: the site of action potential initiation. Has the lowest threshold of any part of the neuron.
Axon Terminals (Synaptic End Bulbs)
Swellings at the axon's end that contain synaptic vesicles filled with neurotransmitters. When an action potential arrives, vesicles fuse with the membrane and release their contents into the synaptic cleft.
Myelin Sheath
A fatty insulating wrap around the axon that speeds up signal transmission dramatically. Formed by Schwann cells in the PNS and oligodendrocytes in the CNS. Absent at nodes of Ranvier.
Nodes of Ranvier
Tiny gaps in the myelin sheath, spaced regularly along the axon. Packed with voltage-gated Na+ channels. The action potential "jumps" from node to node during saltatory conduction, greatly increasing speed.
1.3 Glial Cells (Neuroglia)
Neurons share the nervous system with glial cells, support cells that outnumber neurons roughly 10:1. In the human brain, neurons make up only about 10 percent of the cells, while the remaining 90 percent are glia cells. Glia do not generate action potentials, but they perform critical housekeeping functions: forming myelin, maintaining the chemical environment neurons need, clearing debris, and forming the blood-brain barrier. The name comes from the Greek word for "glue."
Astrocytes
Star-shaped; the most numerous glial type. They maintain the blood-brain barrier, regulate extracellular ion concentrations (especially K+), provide metabolic support to neurons, and clean up excess neurotransmitters from synapses (reuptake). Also guide neuron migration during development.
Oligodendrocytes
Produce myelin in the CNS (brain and spinal cord). One oligodendrocyte can myelinate segments of up to 50 different axons simultaneously. Damage to these cells causes the demyelinating disease multiple sclerosis.
Schwann Cells
Produce myelin in the PNS (peripheral nerves). Unlike oligodendrocytes, each Schwann cell myelinates only one segment of one axon. Also produce neurilemma, which guides axon regrowth after PNS injury: PNS regeneration is possible; CNS regeneration is poor.
Microglia
The brain's immune defense system. Small, highly mobile cells that survey the CNS for damage or infection. They migrate to sites of injury, engulf dead neurons and debris (phagocytosis), and release inflammatory signals. Derived from macrophages, not neural tissue.
Ependymal Cells
Line the ventricles of the brain and the central canal of the spinal cord. Produce and circulate cerebrospinal fluid (CSF), which cushions the brain, removes waste, and provides nutrients. Their cilia beat rhythmically to circulate CSF.
Oligodendrocytes: CNS Myelin
- Found in brain and spinal cord
- One cell myelinates up to 50 axon segments
- Damage → Multiple Sclerosis
- CNS axons regenerate poorly after damage
- No neurilemma produced
Schwann Cells: PNS Myelin
- Found in peripheral nerves only
- One cell myelinates one axon segment only
- Damage → Guillain-Barré syndrome
- PNS axons can regenerate (neurilemma guides regrowth)
- Produce neurilemma sheath
1.4 The Resting Membrane Potential
When a neuron is not firing, the inside of its membrane sits at approximately −70 mV relative to the outside. This voltage difference, the resting membrane potential, exists because ions are unequally distributed across the membrane. The inside is negatively charged relative to the outside: a state called polarization. The resting potential is maintained by the selective permeability of the membrane to ions and the active Na+/K+ ATPase pump.
The neural membrane itself is double-layered. It is composed of phospholipid molecules arranged so that their fatty acid "tails" (which are hydrophobic) turn toward each other, forming an insulating barrier that prevents ions from crossing except through specific channels.
Two forces drive ion movements: diffusion (ions move from high to low concentration) and electrostatic pressure (ions are attracted to opposite charges). The balance point for each ion, where these two forces cancel out, is the equilibrium potential for that ion.
Ion Distribution and Why the Interior Is Negative
| Ion | Higher Concentration | Membrane Permeability at Rest | Effect |
|---|---|---|---|
| Potassium (K+) | Inside the cell (~140 mM) | High: K+ leak channels always open | K+ diffuses out, leaves negative charge inside, main reason for negative resting potential |
| Sodium (Na+) | Outside the cell (~145 mM) | Very low at rest (channels closed) | Cannot enter freely; contributes to positive exterior |
| Chloride (Cl−) | Outside the cell | Moderate | Negative ions outside further reinforce exterior positive charge |
| Organic Anions (A−) | Inside the cell | Cannot cross membrane (too large) | Trapped negative proteins and nucleotides add to interior negativity |
The Na+/K+ ATPase pump is the engine that maintains these gradients. It uses ATP to actively transport 3 Na+ ions out and 2 K+ ions in per cycle. Because it exports more positive charges than it imports, it contributes directly to the negative interior. The pump also counteracts the slow leak of ions that would otherwise collapse the gradients over time.
1.5 The Action Potential
An action potential is a rapid, self-propagating reversal of membrane polarity that travels the length of an axon. It is the neuron's output signal: an all-or-nothing electrical event. When enough depolarizing current reaches the axon hillock to push the membrane potential above the threshold, voltage-gated Na+ channels snap open and the action potential begins.
Membrane Voltage States
Polarized (Resting)
The normal resting state: inside is approximately −70 mV. The membrane is polarized, a charge difference exists across it. The neuron is ready to fire but not currently firing.
Depolarized
The membrane potential has become less negative (moved toward 0 mV, e.g., −67 mV). Na+ channels have begun to open, allowing positive ions to enter. Sufficient depolarization triggers an action potential.
Completely Depolarized
The membrane potential has reached and overshot 0 mV, peaking at approximately +40 to +50 mV. Voltage-gated Na+ channels are fully open at this point: the peak of the action potential.
Hyperpolarized
The membrane potential has become more negative than the resting level (e.g., −72 mV or beyond). Caused by K+ channels remaining open after repolarization or by IPSP activity. The neuron is temporarily less excitable.
An action potential either occurs fully or not at all. There is no "partial" action potential. Once the membrane potential crosses threshold (approximately −55 mV), the process fires to completion with the same peak voltage every time, regardless of the strength of the stimulus. Stimulus intensity is coded not by the size of each action potential but by the frequency of firing (rate coding).
Phases of the Action Potential
Threshold (~−55 mV)
The critical voltage at which voltage-gated Na+ channels open en masse. Below threshold, small depolarizations dissipate without triggering an AP. At threshold, the response becomes self-regenerating and unstoppable.
Depolarization (Rising Phase)
Voltage-gated Na+ channels open, allowing Na+ to rush into the cell (driven by both concentration gradient and electrical attraction). The membrane potential rapidly swings from −70 mV to +40–50 mV in under 1 millisecond.
Repolarization (Falling Phase)
Na+ channels inactivate (close). Voltage-gated K+ channels open, and K+ rushes out, carrying positive charge with it. The membrane potential rapidly falls back toward the resting level.
Hyperpolarization (Undershoot)
K+ channels remain open slightly too long, so K+ continues to exit beyond the resting point. The membrane potential briefly dips below −70 mV (e.g., −75 mV). The neuron is temporarily less excitable during this phase.
Refractory Periods
After an action potential fires, the neuron temporarily cannot fire again (absolute refractory period) or can only fire with a much stronger-than-normal stimulus (relative refractory period). These periods are critical: they set a maximum firing rate and are the reason action potentials travel only in one direction.
Absolute Refractory Period
- Immediately follows the action potential peak
- Na+ channels are inactivated, cannot open regardless of stimulus
- No new action potential is possible
- Lasts approximately 1–2 milliseconds
- Sets the upper limit on firing rate (~500–1000 AP/s)
Relative Refractory Period
- Follows the absolute refractory period
- Na+ channels have recovered; K+ channels still partly open
- An AP can fire but requires a stronger-than-normal stimulus
- Lasts several additional milliseconds
- Membrane is hyperpolarized during this phase
1.6 Propagation: How Action Potentials Travel
An action potential does not physically move: it is regenerated at each successive point along the axon. Each depolarized segment depolarizes the next adjacent segment through local current flow. In unmyelinated axons this happens continuously. In myelinated axons, the process jumps between nodes of Ranvier, a much faster strategy called saltatory conduction.
Continuous Conduction (Unmyelinated)
- AP regenerated at every point along axon membrane
- Slow: typically 0.5–2 m/s
- Found in C fibers (pain, temperature)
- No myelin; entire axon surface is active
- More energy consumed per unit length
Saltatory Conduction (Myelinated)
- AP "jumps" from node to node (Ranvier gaps)
- Fast: up to 70–120 m/s in large myelinated axons
- Found in A fibers (motor, touch, proprioception)
- Myelin insulates between nodes; Na+ channels concentrated at nodes
- More energy efficient: ions exchanged only at nodes
"Saltatory" comes from the Latin saltare (to jump). Because the electrical signal skips across insulated myelin segments and only needs to regenerate at the small, ion-channel-rich nodes of Ranvier, the process is both faster and more metabolically efficient than continuous conduction. Loss of myelin (as in multiple sclerosis) slows or blocks conduction entirely.
1.7 The Synapse: Structure and Transmission
A synapse is the junction where one neuron communicates with another neuron, a muscle, or a gland. The term was coined by the British physiologist Charles Sherrington (1897). Most synapses in the brain are chemical synapses: information crosses the gap not as an electrical signal but as a molecular signal carried by neurotransmitters. A minority are electrical synapses (gap junctions), where ions pass directly between cells.
A junction between a presynaptic neuron and a postsynaptic cell, separated by a synaptic cleft (~20–40 nm wide). When an action potential reaches the presynaptic terminal, it triggers calcium-dependent release of neurotransmitters into the cleft. Neurotransmitters then bind to receptors on the postsynaptic membrane, producing either excitation or inhibition.
Anatomy of a Chemical Synapse
Steps of Synaptic Transmission
Postsynaptic Potentials: EPSP and IPSP
A single synapse generates a graded potential in the postsynaptic membrane, not an action potential. Whether the postsynaptic cell eventually fires depends on the sum of all incoming signals. Graded potentials are unlike action potentials: they vary in size, do not follow the all-or-none law, and decay with distance.
EPSP: Excitatory Postsynaptic Potential
- Depolarizes the postsynaptic membrane
- Moves membrane potential toward (not past) threshold
- Caused by excitatory NTs (e.g., glutamate, acetylcholine)
- Opens Na+ or Ca²⁺ channels: positive ions enter
- Makes an action potential more likely
IPSP: Inhibitory Postsynaptic Potential
- Hyperpolarizes the postsynaptic membrane
- Moves membrane potential away from threshold
- Caused by inhibitory NTs (e.g., GABA, glycine)
- Opens K+ or Cl− channels: interior becomes more negative
- Makes an action potential less likely
Temporal summation: Multiple signals arrive at the same synapse in rapid succession. Each EPSP adds to the previous one before it fades, potentially reaching threshold together. Spatial summation: EPSPs from multiple different synapses arrive simultaneously and add together at the axon hillock. The neuron fires when the combined postsynaptic potential crosses threshold, regardless of whether that is achieved by temporal or spatial means.
Clearing Neurotransmitters from the Synapse
Reuptake
The most common mechanism. The presynaptic terminal actively pumps released neurotransmitters back into itself for repackaging and reuse. Transporter proteins in the presynaptic membrane perform this. Drugs that block reuptake (e.g., SSRIs blocking serotonin reuptake) prolong NT action.
Enzymatic Degradation
Enzymes in the synaptic cleft or postsynaptic membrane break the NT into inactive fragments. Example: acetylcholinesterase rapidly degrades acetylcholine into choline and acetate. Organophosphate poisons (nerve agents) work by blocking this enzyme.
Diffusion
Some NT molecules simply drift away from the synapse into the extracellular space, reducing their concentration at the receptor site. Less common as the primary clearance mechanism; slow and imprecise.
1.8 Neurotransmitters
A neurotransmitter is a chemical messenger released from the presynaptic terminal that carries signals across the synaptic cleft to postsynaptic receptors. Each neurotransmitter binds to specific receptor proteins using a lock-and-key mechanism: only NTs that fit the receptor's shape can bind and trigger a response. This specificity explains why the same NT can have different effects in different brain regions depending on which receptor subtype is present.
Neurotransmitters (and other chemical messengers) bind receptors with high specificity: the NT's molecular shape fits the receptor like a key fits a lock. This principle applies to olfaction as well: the lock-and-key theory of olfaction (also called the Odotope theory) proposes that each type of olfactory receptor is shaped to accept only certain odorant molecules, explaining how we distinguish thousands of different smells.
Classification of Neurotransmitters
| Class | Examples | Notes |
|---|---|---|
| Amino Acids | Glutamate, GABA, Glycine, Aspartate | Most abundant in the CNS; fast-acting; ionotropic receptors predominate |
| Catecholamines (Monoamines) | Dopamine, Norepinephrine, Epinephrine | Derived from tyrosine; often modulatory; slow-acting via G-protein receptors |
| Indoleamines (Monoamines) | Serotonin (5-HT), Melatonin | Derived from tryptophan; regulate mood, sleep, appetite |
| Quaternary Amines | Acetylcholine (ACh) | Contains a quaternary nitrogen; neuromuscular junction + CNS |
| Neuropeptides | Endorphins, Substance P, Oxytocin, Enkephalins | Large molecules; slow and long-lasting; often co-released with fast NTs |
| Purines | Adenosine, ATP | Adenosine is inhibitory (caffeine blocks adenosine receptors); ATP is excitatory |
Major Neurotransmitters: Functions and Locations
| Neurotransmitter | Type | Effect | Clinical Link |
|---|---|---|---|
| Glutamate | Amino acid | Excitatory (main) | Excess → excitotoxicity; key in LTP and memory |
| GABA | Amino acid | Inhibitory (main) | Low GABA → anxiety, seizures; benzodiazepines enhance GABA |
| Glycine | Amino acid | Inhibitory | Strychnine blocks glycine receptors → spasms; mainly spinal cord |
| Acetylcholine (ACh) | Quaternary amine | Excitatory (NMJ); mixed in CNS | ACh deficit → Alzheimer's; Parkinson's has ACh/DA imbalance |
| Dopamine (DA) | Catecholamine | Modulatory | DA deficit → Parkinson's; DA excess → schizophrenia |
| Serotonin (5-HT) | Indoleamine | Modulatory (mainly inhibitory) | Low serotonin → depression; SSRIs block reuptake |
| Norepinephrine (NE) | Catecholamine | Modulatory (excitatory/inhibitory) | Role in arousal, attention, stress response |
| Endorphins | Neuropeptide | Inhibitory (Modulatory) | Endogenous opioids; pain relief; runner's high |
Neurotransmitter Origins in the Brain
| Neurotransmitter | Primary Source | Key Exam Point |
|---|---|---|
| Dopamine | Substantia nigra (nigrostriatal); VTA (mesolimbic/mesocortical) | Substantia nigra loss → Parkinson's; excess → schizophrenia |
| Serotonin | Raphe nuclei (midbrain through medulla) | Most directly tested origin; projects throughout CNS |
| Norepinephrine | Locus coeruleus (pons) | Arousal and attention; broad cortical and spinal projections |
| Acetylcholine | Basal forebrain (nucleus basalis of Meynert); brainstem nuclei | Basal forebrain degeneration → Alzheimer's memory deficit |
| GABA | Interneurons throughout CNS | Most widely distributed inhibitory NT; no single nucleus of origin |
| Glutamate | Cortical pyramidal neurons; hippocampus; distributed | Primary excitatory NT; mediates LTP at NMDA receptors |
| Epinephrine / NE | Adrenal medulla (peripheral; not a brain structure) | Released into bloodstream during stress (fight-or-flight) |
1.9 Synaptic Plasticity and Long-Term Potentiation
The strength of a synapse is not fixed: it changes with use. Synaptic plasticity is the ability of synapses to strengthen or weaken over time in response to activity. This is the cellular mechanism underlying learning and memory. The most studied form of plasticity is Long-Term Potentiation (LTP).
A lasting increase in the strength of synaptic transmission that follows high-frequency, high-intensity stimulation of a presynaptic neuron. First described by Bliss and Lømo (1973) in the hippocampus. LTP is considered the leading cellular model for how the brain encodes long-term memories. The key neurotransmitter is glutamate, acting at NMDA receptors.
During LTP, repeated glutamate release causes NMDA receptors to open and allow Ca²⁺ into the postsynaptic cell. This calcium influx triggers a cascade of changes: increased sensitivity of NMDA receptors, insertion of more AMPA receptors into the postsynaptic membrane, and eventually presynaptic changes that strengthen NT release. The result is a synapse that fires more easily for days or weeks after the initial stimulation.
Glutamate and LTP
Glutamate is the neurotransmitter responsible for synaptic plasticity and LTP. It acts on two receptor types: AMPA receptors (fast excitation) and NMDA receptors (calcium-permeable; the "coincidence detector" that opens only when both pre- and postsynaptic activity occur simultaneously).
Hebbian Plasticity
The principle: "neurons that fire together, wire together." Proposed by Donald Hebb (1949). When a presynaptic neuron repeatedly activates a postsynaptic neuron, the synapse between them strengthens. LTP is the physiological evidence for this principle.
Long-Term Depression (LTD)
The opposite of LTP: low-frequency stimulation weakens synapses. LTD is equally important in synaptic plasticity, helping fine-tune neural circuits by eliminating ineffective connections. Plays a role in cerebellum-dependent motor learning.
Landmark Research
Kandel's Aplysia Research
Eric Kandel used the sea slug Aplysia californica (chosen for its large, identifiable neurons) to show that synaptic changes are the cellular basis of learning and memory. Repeated stimulation caused measurable changes in synaptic strength, demonstrating that habituation weakens synapses (fewer vesicles released) and sensitization strengthens them (more vesicles released). This supported Hebb's principle at the cellular level and earned Kandel the Nobel Prize (2000). PYQ: "Kandel's studies on Aplysia were used to support the hypothesis that ___" → synaptic plasticity underlies learning.
Cortical Spreading Depression and Amnesic Agents
Cortical spreading depression (CSD) is a slow wave of depolarisation followed by sustained inhibition that spreads across the cortex. Induced experimentally by agents such as potassium chloride (KCl). In memory consolidation research, CSD acts as an amnesic agent: the wave of inhibition disrupts consolidation processes, causing amnesia for material learned just before or after its induction. Distinct from LTP/LTD; CSD is used to study the timing window for memory consolidation.
Non-Associative Learning
Non-associative learning occurs when an organism is exposed to a single repeated stimulus and its response changes over time, without any pairing of two stimuli. The two key forms are habituation and sensitisation, both demonstrated by Kandel in Aplysia.
Habituation
- Repeated presentation of a non-threatening stimulus
- Response gradually decreases over time
- Neural basis: Ca²⁺ influx decreases → fewer vesicles released
- Result: synaptic depression
- Example: no longer startling at a repeated harmless sound
Sensitisation
- Exposure to an intense or noxious stimulus
- Response to subsequent stimuli is heightened
- Neural basis: interneurons activated → increased Ca²⁺ influx → more NT released
- Result: synaptic facilitation
- Example: heightened startle response after a painful shock
High-Frequency Topics
Previous Year Questions
Match the following: List I: a. -67 mv b. +45 mv c. -70 mv d. -72 mv List II: i) Polarized ii) Hyperpolarized iii) Depolarized iv) Completely depolarized
Assertion (A): Neurons cannot fire during the absolute refractory period. Reason (R): A neuron can release only one neurotransmitter.
Afferent and Efferent nerves are found in which of the following?
Theorist → Concept Reference
| Researcher | Year | Contribution | Key Term |
|---|---|---|---|
| Charles Sherrington | 1897 | Coined the term "synapse"; studied synaptic integration | Synapse; spatial/temporal summation; EPSP/IPSP concept |
| Alan Hodgkin & Andrew Huxley | 1952 | Described ionic basis of the action potential; Nobel Prize 1963 | Voltage-clamp; Na+/K+ conductance; Hodgkin-Huxley model |
| Donald Hebb | 1949 | Proposed Hebbian learning rule for synaptic strengthening | "Neurons that fire together, wire together"; Hebb synapse |
| Bliss & Lømo | 1973 | Discovered long-term potentiation (LTP) in hippocampus | LTP; high-frequency stimulation; enduring synaptic facilitation |
| Otto Loewi | 1921 | First demonstrated chemical neurotransmission (Nobel 1936) | Vagusstoff (later identified as acetylcholine); chemical synapse |
| Henry Dale | 1914 | Identified acetylcholine; Dale's Principle (one NT per neuron, now known to be oversimplified) | Acetylcholine; muscarinic/nicotinic receptors |
| Santiago Ramón y Cajal | 1890s | Established the Neuron Doctrine: nervous system is made of individual cells, not a syncytium | Neuron doctrine; dendritic spines; neural circuits |