Nerve Runner: Impulse Express

A nod to Manic Miner (Bug-Byte, 1983) and Jet Set Willy (Software Projects, 1984), with their ladders, ropes, conveyor belts and crumbling floors, and to Skool Daze (Microsphere, 1984), whose characters wander about and talk in speech bubbles. You’re a nerve impulse, and the jobs come in any order, as in Skool Daze. Off the main path, there are eight Nobel medals to find and two puzzles worth extra points. Finish quickly for a speed bonus. The talking cells, each with a job and a personality, are a nod to Once Upon a Time… Life (Il était une fois… la vie, 1987). On Hard your ATP runs down, like the air in Manic Miner. The game is saved in your browser, so you can carry on another day.

The science

• Reflex: heat receptors in the fingertip, with TRPV1 channels, fire at painful heat. In the spinal cord, the dorsal horn passes the signal through an interneuron to the motor neurons, and the hand moves before the brain has felt anything.
• Fright and calm: the sympathetic chain speeds the heart with noradrenaline, and the adrenal glands add adrenaline in the blood. The vagus nerve slows it again with acetylcholine, acting on the heart’s pacemaker, the sinoatrial node.
• Waving: the motor cortex, with its giant Betz cells, sends the command down the corticospinal tract to the motor neurons of the ventral horn. At the neuromuscular junction, the nerve ending makes acetylcholine from choline (eggs are a good source), and acetylcholinesterase breaks it down again in a fraction of a millisecond.
• Remembering: in the hippocampus, glutamate opens AMPA receptors. The NMDA receptor needs glutamate and a depolarised membrane at once, which pushes out the magnesium ion that blocks it. Calcium comes in and the synapse grows stronger: long-term potentiation.
• Along the way: myelin from oligodendrocytes and Schwann cells lets the impulse leap from one node of Ranvier to the next; astrocytes tidy up glutamate; the gut has its own enteric nervous system. The ladders are microtubules and the conveyor belts axonal transport. The hazards: tetrodotoxin from the pufferfish, which blocks sodium channels, and GABA, the brain’s main “stop” messenger. Patches without myelin crumble, as in multiple sclerosis.
• Getting about: a sodium channel in a doorway opens, then shuts its pore for a moment (inactivation) before it can open again. That pause, the refractory period, is why an impulse never turns back. Nodes of Ranvier throw you along, as in saltatory conduction (from the Latin saltare, to leap). The rose thorns in the fingertip are what nociceptors are for.
• Energy: the sodium–potassium pump keeps the membrane ready to fire, and it runs on ATP from mitochondria. In the heart, where about a third of each muscle cell is mitochondria, the electron transport chain runs along the floor: complex I (or complex II), complex III and complex IV pass electrons to oxygen and pump protons, and the protons flow back through ATP synthase. On this site: type II NADH dehydrogenase, a one-protein stand-in for complex I in many bacteria; the caa3 cytochrome c oxidase, a complex IV; and the F1 head of ATP synthase.
• More characters: the cone snail hunts fish with a venomous harpoon, and its conotoxins block the acetylcholine receptors at the neuromuscular junction; a toxin from another cone snail became a painkiller, ziconotide. The control-room operators show the motor homunculus: the hands and lips get the biggest share of the motor cortex. Each synaptic vesicle carries a parcel of about 10,000 acetylcholine molecules.
• Extra quests: the adrenal medulla is a sympathetic ganglion that became a gland: a signal down the splanchnic nerves releases acetylcholine onto its chromaffin cells, and they pour adrenaline into the blood. The hypothalamus is the body’s thermostat (thermoregulation): when Alex is too warm, sympathetic nerves, unusually using acetylcholine, switch on the sweat glands, and the sweat cools the skin as it evaporates.
• Gags with science inside, in the spirit of the series’ episode on neurons: the brainstem’s cough centre holds a vote, because a neuron really does add up its inputs and fire when they cross a threshold (summation); impulses race and bump into each other along the corticospinal tract; and in the dorsal horn, enkephalins, the body’s own opioids, act as traffic police that slow pain down.
• The extras: the medals are for Golgi and Cajal (1906), Sherrington and Adrian (1932), Loewi and Dale (1936), Erlanger and Gasser (1944), Hodgkin, Huxley and Eccles (1963), Katz, von Euler and Axelrod (1970), Kandel, Carlsson and Greengard (2000), and Julius and Patapoutian (2021). “Fast or slow?” is about nerve conduction velocity: thick, myelinated fibres are the fastest. “Loewi’s dream” is his 1921 frog-heart experiment, the first proof that nerves talk with chemicals. Take the medals to the thalamus, which relays nearly every sense to the cortex (smell mostly takes a short cut). Here it’s dressed as the Blue Hall of Stockholm City Hall, where the Nobel banquet is held every 10 December; the prizes are handed out earlier that day at the Stockholm Concert Hall. The Blue Hall is red brick: the architect, Ragnar Östberg, meant to plaster it blue, but liked the brick too much.

Where the game cuts corners

• A nerve impulse doesn’t travel from the brain to the gut and back. Each one runs along a single neuron, in one direction, and is gone in a few milliseconds; the next neuron starts a new one.
• Nobody carries neurotransmitters about. They’re made and stored in the nerve ending that releases them, and choline reaches it through the blood, not in someone’s arms.
• The heart doesn’t go straight from 72 to 130 and back with one delivery. It changes a little with every breath, too.
• A real reflex takes about a tenth of a second, not a run through four screens. Alex would be very burnt otherwise.
• A sodium channel opens because the voltage across the membrane changes, not on a timer, and it stays open for about a millisecond, not a second and a half. Its plug is a short loop of the same protein; the “ball on a chain” picture fits some potassium channels better.
• Nodes of Ranvier don’t throw anything. The impulse only seems to leap: the current runs quickly under the myelin and has to be rebuilt just at each node.
• Botanists would say roses have prickles, not thorns. Your fingertip won’t care.
• The thalamus sees almost every guest, but it doesn’t hold banquets.
• ATP doesn’t run out in a minute: the body makes about its own weight in ATP every day, by recycling the same molecules over and over.
• Cone snails live in warm seas, not in anyone’s arm. If you ever meet one, look but don’t touch.
• There’s no control room in the motor cortex, and nobody there wears a headset. Each part of the body does have its own patch, though.
• Nobody rides a drop of sweat up to the skin, though it would be a short trip: the gland sits only a few millimetres down.
• Neurons don’t vote, and there are no committee meetings in the brainstem. But a neuron does add up the signals telling it to fire and to keep quiet, and fires only when the total is big enough. Majority rules, more or less.