Nervous system

• 1. Introduction

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  The nervous system is the part of an animal that carries signals to and from every corner of its body. In the simplest worms it amounts to a few hundred cells. In African elephants it swells to around 300 billion. Yet for all this complexity, no one knew until approximately the year 1900 that neurons are the basic units of the brain. The idea that the brain communicates chemically did not arrive until around 1930. We did not grasp the action potential, the electrical signal neurons use to talk to one another, until the 1950s. So how does a system this old and this universal still hold so many puzzles? This documentary follows the cell that defines it, the synapses that join those cells, the long evolutionary road from sponges to elephants, and the moments when a single neuron can hurl a fish out of danger in milliseconds.

• 2. The Cell That Defines It

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  The neuron is the special cell whose presence defines nervous tissue. What sets it apart from every other cell is the synapse, a membrane-to-membrane junction packed with molecular machinery for rapid signalling. Many neurons grow an axon, a protoplasmic protrusion that can reach distant parts of the body and make thousands of synaptic contacts. These axons travel through the body in bundles, and those bundles are the nerves themselves. Even within a single species such as humans, hundreds of different types of neuron exist, each with its own shape and job. Sensory neurons convert physical stimuli like light and sound into neural signals. Motor neurons convert neural signals into the activation of muscles or glands. In many species, though, the great majority of neurons take input only from other neurons and pass their output to still more neurons. Neurons do not work alone. Alongside them sit glial cells, named from the Greek for glue, which provide support and nutrition and maintain homeostasis. In the human brain, the total number of glia is estimated to roughly equal the number of neurons. One important type, the oligodendrocytes of the central nervous system and the Schwann cells of the peripheral nervous system, wraps axons in a fatty substance called myelin. That insulation lets axons carry action potentials far more rapidly. Recent findings show that glia like microglia and astrocytes also act as resident immune cells inside the central nervous system.

• 3. How One Cell Talks To Another

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  Acetylcholine released at a single contact between a motor neuron and a muscle cell triggers rapid contraction. That moment captures the nervous system's defining trick: point-to-point signalling. Instead of broadcasting hormones into the circulation to diffuse toward distant sites, neurons project axons to specific targets and connect with specific cells. Neural signalling is therefore far more precise than hormonal signalling, and far faster. The quickest nerve signals travel at speeds exceeding 100 meters per second. Synapses come in two kinds, electrical and chemical, and the chemical ones are both more common and more varied. At a chemical synapse, the sending cell is called presynaptic and the receiving cell postsynaptic. The presynaptic terminal holds tiny spherical synaptic vesicles filled with neurotransmitter. Electrical stimulation spills their contents into the narrow synaptic cleft, where the neurotransmitter binds receptors on the postsynaptic membrane. The whole transmission takes only a fraction of a millisecond, though its effects can last far longer. There are over a hundred known neurotransmitters, and many have multiple receptor types, yielding hundreds of synapse varieties. Glutamate's receptors are all excitatory or modulatory, while GABA's are all inhibitory, which is why glutamatergic cells get called excitatory neurons and GABAergic cells inhibitory ones. Strictly, that is an abuse of terminology, since the receptors are excitatory or inhibitory, not the neurons. A rule called Dale's principle holds that a neuron releases the same neurotransmitters at all its synapses, with only a few known exceptions.

• 4. Memory In The Synapse

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  Long-term potentiation, abbreviated LTP, is the best-known form of neural memory, and it was discovered in 1973. It works at synapses that use glutamate acting on a special receptor known as the NMDA receptor. That receptor has an associative property. If both cells in the synapse fire at roughly the same time, a channel opens and lets calcium flow into the target cell. The calcium triggers a second messenger cascade that raises the number of glutamate receptors in the target cell, strengthening the synapse. This change can last for weeks or longer. Since 1973, many other synaptic memory traces have been found, strengthening or weakening connections under varying conditions for variable lengths of time. The reward system, which reinforces desired behaviour, depends on a variant of LTP. It is conditioned on an extra input from a reward-signalling pathway that uses dopamine as its neurotransmitter. Taken together, these forms of synaptic modifiability give rise to neural plasticity, the capacity of the nervous system to adapt to changes in its environment. That adaptability has a striking limit in at least one creature, where the nervous system is fixed entirely by the genome.

• 5. From Sponges To Elephants

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  Sponges have no neurons and no nervous system at all, and the same is true of placozoans and mesozoans, all of which have very simple body plans. Yet sponge cells carry homologs of many genes central to synaptic function, and they form a structure resembling a postsynaptic density whose purpose is still unclear. They communicate through calcium waves that drive simple acts like whole-body contraction. Jellyfish, comb jellies, hydras and corals take a different path with a diffuse nerve net rather than a central nervous system. In most jellyfish that net spreads evenly across the body, while in comb jellies it concentrates near the mouth. The net combines sensory neurons, motor neurons that contract the body wall, and intermediate neurons that read patterns of sensory activity. Radiata build their neurons from only two primordial cell layers, endoderm and ectoderm. The vast majority of living animals are bilaterians, with left and right sides that mirror each other. All bilateria are thought to descend from a common wormlike ancestor that appears as fossils in the Ediacaran period, between 550 and 600 million years ago. Their basic body is a tube running from mouth to anus, with a nerve cord bearing a ganglion for each segment and an especially large front ganglion, the brain. Even humans keep this segmented plan, with the top three segments forming the forebrain, midbrain, and hindbrain. Bilaterians split into protostomes and deuterostomes, distinguished by events early in embryonic development. Protostomes such as insects carry their nerve cord on the ventral side, while deuterostomes including vertebrates carry it on the dorsal side. Most anatomists now hold that the two groups are flipped over relative to each other, a hypothesis first proposed by Geoffroy Saint-Hilaire comparing insects to vertebrates.

• 6. Worms And Insects

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  Earthworms reveal the bilaterian plan at its plainest, with dual nerve cords that run the body's length and merge at the tail and mouth. Transverse nerves connect those cords like the rungs of a ladder, coordinating the animal's two sides. Two ganglia at the head form a nerve ring that works like a simple brain, while photoreceptors on the eyespots report light and dark. One roundworm has gone further into the record than any other animal. The nematode Caenorhabditis elegans has had its entire nervous system mapped into a connectome that includes its synapses, with every neuron and its lineage recorded. Its nervous system is sexually dimorphic. Males have exactly 383 neurons, while hermaphrodites have exactly 302. Because every neuron in C. elegans is uniquely identifiable in the same place with the same connections in every worm, its nervous system is completely specified by the genome, with no experience-dependent plasticity. Arthropods such as insects and crustaceans build their nervous system from a chain of ganglia linked by a ventral nerve cord of two parallel connectives running along the belly. The head segment holds the brain, also called the supraesophageal ganglion, which in insects divides into the protocerebrum, deutocerebrum, and tritocerebrum. Behind it sits the subesophageal ganglion, three pairs of fused ganglia that control the mouthparts, salivary glands, and certain muscles. In insects many cell bodies are electrically passive, sitting at the brain's edge to provide metabolic support while the real signal processing happens in an interior tangle of fibers called neuropil.

• 7. The Cell With A Name

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  A neuron is called identified when its properties set it apart from every other neuron in the animal, and when each individual of the species has exactly one neuron with that set of properties. In human nervous systems there are believed to be none. The best known identified neurons in vertebrates are the gigantic Mauthner cells of fish. Every fish has two, sitting low in the brainstem, one on the left and one on the right. Each Mauthner cell sends an axon that crosses over and travels down the spinal cord, making numerous connections along the way. Its synapses are so powerful that a single action potential drives a major behavioral response. Within milliseconds the fish curves into a C-shape, then straightens, propelling itself rapidly forward. This is a fast escape response, triggered most easily by a strong sound or pressure wave striking the lateral line organ. Mauthner cells are not the fish's only identified neurons; there are about 20 more types, including pairs of Mauthner cell analogs in each spinal segmental nucleus. Such cells have been described as command neurons, defined as neurons capable of driving a specific behavior on their own. They appear most often in fast escape systems, and the squid giant axon and squid giant synapse, famous for their enormous size in early neurophysiology experiments, both serve the squid's escape circuit. The concept has grown controversial, since some neurons that seemed to fit turned out to evoke a response only in limited circumstances.

• 8. When The System Fails

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  The blood-brain barrier seals the brain and spinal cord off from most chemicals in the bloodstream, while tough meningeal membranes and the bones of the skull and vertebral column shield them physically. These defenses make the central nervous system less susceptible than the peripheral one, but they have a flip side. Damage to the central nervous system tends to carry more serious consequences. Nerves usually run deep, though some lie exposed, like the ulnar nerve near the elbow. They can still be hurt, causing pain, loss of sensation, or loss of muscle control, and a nerve squeezed through a tight bony channel produces conditions such as carpal tunnel syndrome. A completely severed nerve often regenerates, but for long nerves the process may take months. Peripheral neuropathy has many sources beyond physical damage, among them diabetes, the inflammatory condition Guillain-Barre syndrome, vitamin deficiency, infections like leprosy or shingles, and poisoning by heavy metals. Many cases have no identifiable cause and are called idiopathic. The spinal cord offers a harder lesson. If swelling is the only injury, symptoms may pass, but if nerve fibers are actually destroyed, the loss of function is usually permanent. Spinal fibers do try to regrow in the same way other nerve fibers do. The obstacle is scar tissue, which forms where the cord is destroyed and cannot be penetrated by the regrowing nerves.