pastpaperbd/ Biology/ Notes/ Neurons and Synapses
T6

Neurons and Synapses

AQA spec ref: 3.6.2 - Nervous coordination in mammals

The nervous system uses electrical signals (nerve impulses) to rapidly transmit information between receptors, the central nervous system (CNS), and effectors. This allows rapid, precise, and short-lived responses. Contrast this with the hormonal system, which uses chemical signals in the blood for slower, longer-lasting, more widespread responses. Neurons are the cells that carry nerve impulses, and synapses are the junctions where neurons communicate with each other (or with effectors).

Neuron Structure

All neurons share a common plan: a cell body (soma) containing the nucleus, and elongated projections for receiving and transmitting signals.

  • Dendrites - short, branched extensions of the cell body that receive signals from other neurons (dendrites=input)
  • Axon - a single long projection that carries impulses away from the cell body (axon = output). Can be up to 1 metre long.
  • Myelin sheath - a fatty insulating layer formed by Schwann cells wrapping around the axon. Not all neurons are myelinated.
  • Nodes of Ranvier - regular gaps in the myelin sheath where the axon membrane is exposed. Impulses jump between nodes (saltatory conduction).
  • Synaptic knobs (terminal boutons) - bulging ends of axon terminals that contain vesicles of neurotransmitter.

Types of neuron:

  • Sensory neurons - carry impulses from receptors to CNS. Long dendron from receptor, cell body in dorsal root ganglion, axon to spinal cord.
  • Motor neurons - carry impulses from CNS to effectors (muscles/glands). Cell body in spinal cord/brain, long axon to muscle.
  • Relay (interneurons) - connect sensory and motor neurons within the CNS.

Resting Potential

When a neuron is not conducting an impulse, it is at rest. The inside of the axon is at −70 mV relative to the outside - this is the resting potential.

This voltage difference is maintained by:

  1. Na⁺/K⁺ ATPase pump (active transport) - continuously pumps 3 Na⁺ out and 2 K⁺ in per cycle, using ATP. This creates concentration gradients: Na⁺ is high outside, K⁺ is high inside. It also contributes to the negative interior because more positive charge is pumped out than in.
  1. Potassium leak channels - K⁺ channels are partially open at rest, allowing K⁺ to diffuse out down its concentration gradient. This outflow of positive ions further makes the inside more negative.
  1. Large, negatively charged proteins are trapped inside the axon and contribute to the negative internal charge.

The result: the membrane is polarised at −70 mV. Na⁺ channels are closed at rest.

Action Potential

An action potential is a transient reversal of the membrane potential, from −70 mV to approximately +40 mV and back again. It is the nerve impulse.

Generation: Steps in an Action Potential

1. Stimulus and depolarisation:

A stimulus at the receptor end of the neuron opens voltage-gated Na⁺ channels. Na⁺ rushes into the axon down its electrochemical gradient (both concentration gradient and electrical gradient drive it in - Na⁺ is high outside and the inside is negative). The inside of the membrane becomes less negative - this is depolarisation.

2. Threshold and all-or-nothing:

If the membrane depolarises to the threshold (approximately −55 mV), a positive feedback loop begins: depolarisation opens more Na⁺ channels, which causes more Na⁺ influx, which causes more depolarisation. This is an all-or-nothing event - if threshold is not reached, no action potential occurs; if it is reached, a full action potential always fires to the same peak (+40 mV) regardless of stimulus strength.

The peak occurs when Na⁺ channels are fully open and Na⁺ rushes in rapidly.

3. Repolarisation:

At the peak, voltage-gated Na⁺ channels close (they inactivate). Voltage-gated K⁺ channels then open, and K⁺ flows out of the axon down its concentration gradient. This removal of positive charge from the inside restores the negative membrane potential - repolarisation.

4. Hyperpolarisation:

The K⁺ channels are slow to close, so slightly too much K⁺ leaves. The membrane transiently dips below −70 mV - hyperpolarisation (approximately −80 mV).

5. Return to resting potential:

K⁺ channels close. The Na⁺/K⁺ pump restores the original ion gradients. The membrane returns to −70 mV.

The Refractory Period

During and immediately after an action potential, the neuron cannot fire another impulse - this is the refractory period (lasts about 2 - 3 ms). It occurs because:

  • Na⁺ channels are inactivated (they cannot be reopened immediately after closing - they need time to reset)
  • During hyperpolarisation, the membrane is further from the threshold

Why the refractory period matters:

  1. It ensures impulses travel in one direction only - the region behind an impulse is in the refractory period and cannot be re-stimulated, so the impulse can only travel forward.
  2. It limits the maximum frequency of action potentials (sets the upper limit of how many impulses per second).
  3. It ensures that individual impulses remain discrete - they cannot fuse together.

Conduction of Impulses

Unmyelinated neurons conduct impulses by local current flow: the depolarisation at one point causes local electrical currents that depolarise the adjacent membrane, triggering an action potential there. This is slow (approximately 1 m/s) because every point along the axon must undergo the full action potential sequence.

Myelinated neurons conduct impulses by saltatory conduction: the myelin sheath insulates the axon between nodes of Ranvier, so local currents jump from one node to the next, skipping the myelinated sections. Action potentials only occur at the nodes. This is much faster (up to 120 m/s in large myelinated fibres) and more energy efficient (fewer Na⁺/K⁺ pump cycles needed).

Factors affecting conduction speed:

  • Myelination - myelinated=faster (saltatory vs continuous)
  • Axon diameter - wider axon=lower resistance=faster conduction
  • Temperature - higher temperature=faster ion diffusion=faster conduction (up to the thermal denaturation point)

Synaptic Transmission

A synapse is the junction between two neurons (or a neuron and an effector). At most synapses in the mammalian nervous system, transmission is chemical: the electrical signal in one neuron is converted to a chemical signal (neurotransmitter release) and back to an electrical signal in the next.

The gap between the two cells is the synaptic cleft (approximately 20 nm wide). The neuron before the synapse is the pre-synaptic neuron; after is the post-synaptic neuron (or effector cell).

Mechanism of Synaptic Transmission

  1. Action potential arrives at the pre-synaptic knob (synaptic terminal).
  1. Voltage-gated Ca²⁺ channels open in the pre-synaptic membrane. Ca²⁺ ions flood in from the extracellular fluid (where they are at high concentration).
  1. Ca²⁺ triggers vesicle fusion: the calcium ions stimulate synaptic vesicles (each containing ~5000 molecules of neurotransmitter) to move to and fuse with the pre-synaptic membrane - exocytosis.
  1. Neurotransmitter diffuses across the synaptic cleft (20 nm - diffusion is fast over this tiny distance).
  1. Neurotransmitter binds to receptors on the post-synaptic membrane. The receptors are specific for that neurotransmitter - they are ligand-gated ion channels.
  1. Ion channels open in the post-synaptic membrane:
  • If the neurotransmitter is excitatory (e.g. acetylcholine, glutamate): Na⁺ channels open → Na⁺ flows in → post-synaptic membrane depolarises → excitatory post-synaptic potential (EPSP) is generated.
  • If the neurotransmitter is inhibitory (e.g. GABA): Cl⁻ channels open (or K⁺ channels) → makes the interior more negative → inhibitory post-synaptic potential (IPSP) - membrane is harder to depolarise.
  1. Neurotransmitter is removed from the cleft to terminate the signal:
  • Enzymatic breakdown: acetylcholinesterase breaks acetylcholine into choline and acetate in the cleft. The choline is taken back up by the pre-synaptic neuron and used to re-synthesise acetylcholine.
  • Reuptake: some neurotransmitters (e.g. noradrenaline, serotonin) are actively transported back into the pre-synaptic cell intact.
  • Diffusion: neurotransmitter can simply diffuse away from the cleft.

Summation

A single EPSP is usually not large enough to depolarise the post-synaptic membrane to threshold and trigger an action potential. Multiple EPSPs must summate:

  • Temporal summation: multiple impulses arrive in rapid succession at the same synapse, so EPSPs add up over time before the membrane repolarises.
  • Spatial summation: multiple pre-synaptic neurons simultaneously stimulate the same post-synaptic neuron; their EPSPs add up spatially across the membrane.

IPSPs can cancel out EPSPs - this is synaptic inhibition. The post-synaptic cell integrates all incoming signals across all its synapses simultaneously, adding excitatory and inhibitory potentials. An action potential only fires if the combined EPSPs exceed threshold.

Why Synapses are One-Way

Synapses ensure signals travel in one direction because:

  • Neurotransmitter is only released from the pre-synaptic terminal (vesicles are only on this side)
  • Receptors are only on the post-synaptic membrane

The Role of Ca²⁺

Ca²⁺ entry into the pre-synaptic terminal is the direct trigger for vesicle fusion. Evidence: blocking Ca²⁺ channels prevents neurotransmitter release; artificially raising Ca²⁺ concentration inside the terminal causes spontaneous vesicle fusion even without an action potential.

Neurotransmitters

Acetylcholine (ACh): released at all neuromuscular junctions (motor neuron → skeletal muscle) and at many CNS synapses. Binds to nicotinic or muscarinic receptors. Broken down by acetylcholinesterase.

Noradrenaline: released by post-ganglionic sympathetic neurons (fight-or-flight system). Also a neurotransmitter in the brain. Binds to adrenergic receptors.

Dopamine: involved in reward, motivation, movement. Abnormal dopamine signalling → Parkinson's disease (too little) or schizophrenia (complex imbalance).

Serotonin: mood, sleep, appetite regulation. SSRIs (selective serotonin reuptake inhibitors, e.g. fluoxetine/Prozac) block serotonin reuptake, increasing serotonin levels in synaptic clefts.

GABA: the main inhibitory neurotransmitter in the CNS. Opens Cl⁻ channels → hyperpolarisation. Benzodiazepines (e.g. diazepam) enhance GABA's effect.

Drugs and Toxins at Synapses

Many drugs work by mimicking or blocking neurotransmitters at synapses:

  • Nicotine - mimics ACh at nicotinic receptors (agonist). Stimulates post-synaptic neurons, including dopamine reward pathways.
  • Curare - blocks ACh receptors at neuromuscular junction (antagonist) → muscle paralysis.
  • Organophosphate pesticides / nerve agents - inhibit acetylcholinesterase → ACh accumulates in synaptic cleft → continuous stimulation of muscles → convulsions, paralysis.
  • Cocaine - blocks reuptake of dopamine, noradrenaline, and serotonin → their concentrations build up in clefts → excessive stimulation of reward pathways.
  • Opioids (morphine, heroin) - bind to opioid receptors in the CNS, inhibiting pain pathways.

Summary

  • Resting potential: −70 mV; maintained by Na⁺/K⁺ ATPase pump (3Na⁺ out, 2K⁺ in) and K⁺ leak channels
  • Action potential: stimulus → Na⁺ channels open → Na⁺ in → depolarisation → threshold → all-or-nothing. Peak ~+40 mV. Then Na⁺ channels close, K⁺ channels open → K⁺ out → repolarisation → hyperpolarisation → return to −70 mV
  • Refractory period: Na⁺ channels inactivated → ensures directionality, limits frequency, keeps impulses discrete
  • Saltatory conduction: impulses jump between Nodes of Ranvier in myelinated neurons→faster conduction
  • Synaptic transmission: AP → Ca²⁺ in → vesicle fusion → ACh released → diffuses across cleft → binds post-synaptic receptors → ion channels open → EPSP or IPSP → summation → AP (or not) in post-synaptic cell
  • Removal of neurotransmitter: enzymatic breakdown (ACh→choline+acetate) or reuptake
  • Summation: temporal (same synapse, rapid firing) or spatial (multiple neurons)

AQA Exam Tips

  • Resting potential: state −70 mV. Explain: Na⁺/K⁺ pump maintains Na⁺ gradient; K⁺ leak out down gradient; large negative proteins inside. Do not just say "Na⁺/K⁺ pump" - also explain the K⁺ leak.
  • All-or-nothing law: if the threshold potential is reached, a full action potential fires. The size/strength of the stimulus cannot change the amplitude of an action potential, only the frequency of action potentials.
  • Refractory period - three functions: directionality (prevents backward conduction), sets maximum frequency, keeps impulses discrete. AQA may ask for two of these.
  • Synaptic transmission: Ca²⁺ is essential - do not miss this step. AQA specifically asks for the role of calcium.
  • Why signals are unidirectional at synapses: vesicles only in pre-synaptic terminal; receptors only on post-synaptic membrane.
  • Cholinesterase inhibitor effects: acetylcholine is not broken down → stays in cleft → continuous stimulation → muscles cannot relax → spasms. This comes up in the context of nerve agents and organophosphate pesticides.
  • Summation: both types are commonly tested. The key is that a post-synaptic cell integrates all signals and only fires if the net depolarisation exceeds threshold.
  • Myelin and speed: saltatory conduction is faster because the action potential jumps from node to node rather than being generated at every point. This is also more energy efficient.