C2.2 Neural signalling

The two phases of an action potential are controlled by voltage-gated channels: channel proteins that open or close in response to changes in membrane potential (see B2.1 Membranes and membrane transport).

Threshold and depolarization

At the resting potential (−70 mV) the voltage-gated Na⁺ and K⁺ channels are closed. A stimulus, or local currents from a neighbouring active region, makes the membrane potential less negative.

• Below the threshold potential, about −50 mV, few voltage-gated Na⁺ channels open, and the membrane simply returns to rest. No action potential occurs.
• When threshold is reached, voltage-gated Na⁺ channels open. Na⁺ diffuses in, which depolarizes the membrane further, which opens more Na⁺ channels: a positive feedback loop. The potential shoots up to about +30 to +40 mV.

This is why action potentials are all or nothing: once threshold is reached the positive feedback always produces a full-sized action potential, and a stronger stimulus cannot make it bigger.

Repolarization

• At the peak, the Na⁺ channels close (they become inactivated and cannot reopen for a short time).
• The voltage-gated K⁺ channels, which respond more slowly, open. K⁺ diffuses out down its concentration gradient, and the inside becomes negative again.
• The K⁺ channels are also slow to close, so the potential briefly overshoots to about −80 mV (hyperpolarization) before returning to −70 mV.

During this period, the refractory period, that part of the membrane cannot fire again. It makes action potentials separate events and stops them travelling backwards.

How does an action potential in one region trigger the next? Step through the Local currents step of the animation above.

1. In the depolarized region, Na⁺ that has just entered makes the inside positive, while the neighbouring resting region is still negative inside.
2. Na⁺ ions therefore diffuse along the inside of the axon, from the depolarized region towards the resting region next to it.
3. On the outside of the membrane the charges are reversed: the depolarized region is now negative outside, so Na⁺ ions diffuse along the outside towards it, away from the resting region.
4. Both movements reduce the potential difference across the membrane of the neighbouring region, which becomes less negative inside. These ion movements are the local currents.
5. When this region reaches the threshold potential, its voltage-gated Na⁺ channels open and it fires its own action potential.

The process then repeats, region by region, so the action potential travels along the axon. It cannot travel backwards, because the region it has just left is still in its refractory period: its Na⁺ channels cannot reopen yet.

In a wider axon, ions meet less resistance as they diffuse along the inside, so the local currents bring regions further ahead to threshold more quickly. This is the physical reason for the correlation between diameter and speed.

The membrane potential of an axon can be measured with two electrodes, one inside the axon and one in the fluid outside, connected to an oscilloscope (today usually a computer). The trace shows membrane potential (mV) on the y-axis against time (ms) on the x-axis.

Reading the trace

Measuring impulse frequency

Because all action potentials are the same size, information is carried by how often they occur. A stronger stimulus gives a higher frequency of impulses.

• Count the action potentials in a measured time, then divide: frequency = number of impulses ÷ time in seconds.
• Or measure the time from one peak to the next and take 1 ÷ that interval (in seconds).

For example, 5 action potentials in 50 ms (0.05 s) is 5 ÷ 0.05 = 100 impulses per second.

In a myelinated fibre the axon is wrapped by Schwann cells (in the peripheral nervous system), each forming a sheath of many layers of membrane. The lipid-rich myelin is an electrical insulator: ions cannot move across the axon membrane where it is covered.

• The voltage-gated Na⁺ and K⁺ channels and the Na⁺/K⁺ pumps are clustered at the nodes of Ranvier, the short gaps of exposed membrane between Schwann cells, about 1 mm apart.
• Action potentials can therefore occur only at the nodes.
• Local currents flow along the inside of the axon from one node to the next, under the myelin, bringing the next node to threshold.
• The impulse jumps from node to node. This is saltatory conduction (from the Latin saltare, to jump).

In an unmyelinated axon every small region of membrane must depolarize in turn (continuous conduction), which is slow. Saltatory conduction:

• is much faster: up to about 100 m s⁻¹ or more, instead of about 1 m s⁻¹ in a thin unmyelinated fibre;
• uses less energy, because ions cross the membrane only at the nodes, so less ATP is needed to pump them back.

In diseases such as multiple sclerosis, myelin in the central nervous system is damaged, conduction slows or fails, and control of movement is affected.

Many exogenous chemicals (chemicals from outside the body) act at synapses: drugs, pesticides and toxins. They work by affecting release of the neurotransmitter, its binding to receptors, or its removal from the cleft.

Neonicotinoids: blocking transmission

Neonicotinoids, such as imidacloprid, are synthetic insecticides chemically similar to nicotine.

• They bind to nicotinic acetylcholine receptors in the postsynaptic membranes of synapses in the insect central nervous system.
• They bind much more strongly to insect receptors than to mammalian ones, which is why they are relatively less toxic to mammals.
• They bind strongly and are not broken down by acetylcholinesterase, so they stay bound for a long time. The receptors are first overstimulated and then acetylcholine can no longer bind: synaptic transmission is blocked.
• The insect is paralysed and dies.

Because they are taken up by the whole plant, neonicotinoids reach nectar and pollen, and they harm pollinators such as bees as well as pests. For this reason the European Union banned outdoor use of the three main neonicotinoids in 2018.

Cocaine: blocking reuptake

At dopamine synapses in the brain’s reward pathways, dopamine is normally removed from the cleft by dopamine reuptake transporters in the presynaptic membrane.

• Cocaine binds to these transporters and blocks them.
• Dopamine is not reabsorbed, so it accumulates in the synaptic cleft and keeps binding to receptors on the postsynaptic membrane.
• The postsynaptic neurons are stimulated for longer, producing feelings of euphoria and energy.
• Repeated use changes the brain (for example, the number of dopamine receptors falls), which contributes to addiction.

Inhibitory postsynaptic potentials

Not all neurotransmitters excite. Inhibitory neurotransmitters make the postsynaptic neuron less likely to fire. The main one in the brain is GABA (gamma-aminobutyric acid).

• GABA binds to receptors on the postsynaptic membrane that are chloride channels.
• The channels open and Cl⁻ ions diffuse into the neuron, down their concentration gradient.
• Negative charge entering makes the inside more negative than the resting potential, for example −75 mV instead of −70 mV. The membrane is hyperpolarized.

This is an inhibitory postsynaptic potential (IPSP). A hyperpolarized membrane is further from the threshold, so more excitation is needed to make it fire.

Summation

A neuron in the brain may receive synapses from thousands of presynaptic neurons, some excitatory and some inhibitory. A single EPSP is usually far too small to reach threshold. The postsynaptic neuron adds up all its inputs, a process called summation:

• Spatial summation: EPSPs from several different presynaptic neurons arriving at the same time add together.
• Temporal summation: impulses arriving in rapid succession from the same presynaptic neuron produce EPSPs that add together before each one fades.
• IPSPs subtract from the total.

The summed effect is felt at the axon hillock. If the net depolarization there reaches the threshold potential, an action potential starts and travels along the axon; if not, nothing is sent. The output is all or nothing, even though the inputs are graded. Summation is how neurons integrate information and “make decisions”.

Pain receptors: free nerve endings

Pain is detected by sensory neurons whose fine branches end as free nerve endings in the skin, among the cells of the epidermis. They have no specialised receptor cell or capsule: the membrane of the nerve ending itself detects the stimulus.

• The endings contain channels for positively charged ions, such as TRPV1.
• These channels open in response to harmful stimuli: high temperature (above about 43 °C), acid, and certain chemicals, notably capsaicin, the compound that makes chilli peppers taste hot.
• When the channels open, positive ions (Na⁺ and Ca²⁺) diffuse into the ending and depolarize it.
• If the threshold potential is reached, action potentials pass along the sensory neuron to the spinal cord and then to the brain, where the pain is perceived.

Capsaicin opens the same channels as heat, which is why chilli feels burning even though nothing is hot. Pain is not felt in the finger or tongue: the receptor only sends impulses, and the sensation is produced in the brain.

Consciousness as an emergent property

Consciousness, our awareness of ourselves and our surroundings, is perhaps the most remarkable product of the brain. No single neuron is conscious: each just receives, sums and sends signals as described on this page. Consciousness emerges from the interactions of very large numbers of neurons, roughly 86 billion in the human brain, linked by an estimated hundred trillion synapses into networks.

An emergent property is one that a system has but its individual parts do not, arising from how the parts interact. Other examples in biology include the properties of a cell compared with its molecules, or the behaviour of a colony of social insects. Understanding how consciousness emerges is one of the biggest open questions in science.