The Nervous System: Neurons, Signals, Brain and Autonomic Control

1Overview

Touching a hot pan produces a withdrawn hand before the word "ouch" is even formed. In less than a second, receptors in the skin fire, signals race along nerves to the spinal cord, a motor command returns to muscle and the hand moves. That sequence is the nervous system at its simplest: detect, integrate, respond. The nervous system also runs the heartbeat while a person sleeps, adjusts the pupils to a change in light and stores memories. This lesson covers its cells, its electrical and chemical signals, its organization and its role in homeostasis.

2Organization of the nervous system

The nervous system has three basic functions: sensation (detecting stimuli from outside and inside the body), integration (combining sensory input with memory, emotion and context to choose a response) and response (motor output to skeletal, cardiac and smooth muscle, and to glands).

3Neurons and glial cells

Nervous tissue contains two cell types. Neurons carry out communication. Glial cells support neurons; for example, astrocytes help buffer the potassium that neurons release. A neuron has a soma (cell body), branched dendrites that receive most input, and a single axon that carries the signal to its target.

Many axons are wrapped in myelin, a lipid-rich insulating layer. Myelin gives white matter its colour and speeds conduction. In the CNS, gray matter is regions rich in cell bodies and dendrites and white matter is regions dominated by axons. Names differ by location: a cluster of cell bodies is a nucleus in the CNS but a ganglion in the PNS, and a bundle of axons is a tract in the CNS but a nerve in the PNS.

4The action potential: an electrical signal

A neuron at rest is electrically polarized. The inside of the membrane is about -70 mV relative to the outside. Na⁺ is about ten times more concentrated outside the cell, and K⁺ is more concentrated inside. Leakage channels let a little Na⁺ in and K⁺ out, and the sodium-potassium pump (Lesson 3) restores the gradients using ATP.

1. Threshold. A stimulus depolarizes the membrane. If it reaches about -55 mV, voltage-gated Na⁺ channels open. A smaller change fails to trigger anything.
2. Depolarization. Na⁺ rushes in, driven by concentration and electrical gradients, making the inside positive, to about +30 mV.
3. Repolarization. The Na⁺ channels inactivate and voltage-gated K⁺ channels open. K⁺ leaves and the membrane returns toward rest.
4. Hyperpolarization. The K⁺ channels close slightly late, so the membrane briefly dips below -70 mV before the pump and leakage channels restore the resting state.

The whole event lasts about 2 ms and changes the voltage by about 100 mV (0.1 V). Three properties follow.

• All-or-none: either threshold is reached and a full action potential occurs, or nothing happens. Every action potential peaks at about +30 mV. A stronger stimulus produces more action potentials per second, not larger ones.
• Refractory period: while Na⁺ channels are inactivated no new action potential can start (absolute); soon after, a stronger-than-usual stimulus is needed (relative). This keeps signals moving in one direction.
• Propagation: in an unmyelinated axon the signal moves continuously along the membrane, which is slower. In a myelinated axon the signal jumps between nodes of Ranvier (saltatory conduction), which is faster. A wider axon also conducts faster.

5Synapses: from electrical to chemical signal

A synapse is the junction where one neuron communicates with another cell. Some synapses are electrical (cells directly connected so ions pass), but the typical one is chemical.

1. An action potential reaches the axon terminal and opens voltage-gated Ca²⁺ channels.
2. Ca²⁺ entering binds proteins on synaptic vesicles, which fuse with the presynaptic membrane and release neurotransmitter by exocytosis.
3. The neurotransmitter diffuses across the synaptic cleft and binds receptors on the postsynaptic membrane, like a key in a lock.
4. The effect ends when the neurotransmitter is broken down by an enzyme (acetylcholine by acetylcholinesterase), or taken back up by the neuron or by glial cells.

Whether the postsynaptic cell is excited depends on the receptor. An excitatory postsynaptic potential (EPSP) depolarizes the membrane toward threshold; an inhibitory postsynaptic potential (IPSP) hyperpolarizes it away from threshold. A neuron adds its inputs together at the initial segment of the axon. Spatial summation combines inputs from different places, and temporal summation combines repeated inputs from one place that arrive close together. If the total reaches threshold, an action potential fires.

Receptors are either ionotropic (the receptor is itself an ion channel, so the effect is fast) or metabotropic (acting through a G protein and second messenger, so the effect is slower but can alter metabolism or gene expression, and may underlie learning and memory).

In real life. Nicotine binds and activates nicotinic acetylcholine receptors, mimicking acetylcholine. Muscarine from certain mushrooms instead binds muscarinic receptors. Drugs and toxins often act at synapses because a synapse is a place where a molecule can substitute for a transmitter, block a receptor or prevent removal of the transmitter.

6The central nervous system and sensation

From stimulus to perception

Sensation begins at sensory receptors, specialized endings or cells that convert a stimulus into electrical signals. Different receptor types respond to different forms of energy: mechanoreceptors to touch, pressure and stretch, thermoreceptors to temperature, nociceptors to damaging stimuli (pain), chemoreceptors to chemicals such as CO₂ and H⁺, and photoreceptors to light. Receptors inside the body, such as stretch receptors in the walls of the bladder and arteries, supply the information that feedback loops need.

1. A stimulus changes the membrane potential of a receptor (a graded potential).
2. If the change reaches threshold, an action potential travels along a sensory neuron toward the CNS.
3. Synapses pass the signal through the spinal cord or brain stem, usually via the thalamus for conscious senses.
4. The cortex interprets the signal; location of the activity (for example the postcentral gyrus for touch or the occipital lobe for vision) determines what is perceived, and the pattern and frequency of action potentials indicate how strong it is.
5. If a response is needed, motor neurons carry commands to effectors.

Protecting the CNS

The brain and spinal cord are soft and demand a constant, stable chemical environment. They are protected by the skull and vertebral column and by membranes (meninges) and fluid around them. A specialized barrier also controls what enters brain tissue: capillaries in the brain have tight junctions with no gaps between endothelial cells and a thick basement membrane, forming the blood-brain barrier. Small lipid-soluble molecules can cross, while many substances in the blood are kept out and others, such as glucose, enter by specific carrier proteins (Lesson 3). The barrier is one reason that drug design for the brain is difficult.

The brain

The two cerebral hemispheres are connected by the corpus callosum. The cerebellum accounts for about 10% of brain mass.

The spinal cord and reflexes

The spinal cord has posterior (dorsal) regions that receive sensory input and anterior (ventral) regions that send motor output to skeletal muscle; lateral horns in the thoracic, upper lumbar and sacral regions contain autonomic neurons. White columns carry ascending sensory and descending motor tracts. A reflex is a rapid, automatic response handled largely in the cord, which is why the hand withdraws from a hot pan before the brain registers pain. A reflex arc has a receptor, a sensory neuron, an integration centre in the CNS, a motor neuron and an effector.

7The autonomic nervous system

The autonomic system has two divisions that usually act in opposition.

The adrenal medulla acts like a modified sympathetic ganglion: stimulated by preganglionic fibres, it releases epinephrine and norepinephrine into the blood, so the same chemicals act as hormones. Most organs have dual innervation, so their activity reflects the balance of the two divisions. The sympathetic division raises heart rate; the parasympathetic division lowers it. The term "fight or flight" dates from 1915, but the sympathetic system also responds to emotional states, so "fright or freeze" can be included.

8Homeostasis and interdependence

The nervous system is the fast sensor and effector arm of most feedback loops.

• Blood pressure. Baroreceptors in the aorta and carotid arteries report pressure to the medulla, which adjusts heart rate and vessel diameter through the autonomic system (Lesson 8).
• Breathing. The medulla sets the rhythm of breathing and responds to blood CO₂ and pH (Lesson 10).
• Temperature. The hypothalamus compares body temperature with its set point and drives sweating, vasodilation, vasoconstriction and shivering (Lesson 3).
• Digestion. Parasympathetic activity increases motility and secretion; sympathetic activity decreases them, and the enteric network coordinates local reflexes (Lesson 11).
• Endocrine control. The hypothalamus links the nervous and endocrine systems through the pituitary, so many neural signals become hormonal responses (Lesson 7).

In real life. After a stroke or loss of blood flow to the brain, the extracellular K⁺ concentration rises, astrocytes lose their buffering ability and the sodium-potassium pump can fail, so neurons cannot maintain their gradients. In Parkinson disease, loss of dopamine-producing neurons in the substantia nigra disturbs the basal nuclei's control of movement; L-DOPA helps because it can cross the blood-brain barrier and be converted into dopamine. Both conditions show that structure, ions, transmitters and blood supply are linked.

?Quick check

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