Synapses and plasticity
How one neuron changes another, how the connection strengthens or weakens with use, and why that is the mechanism behind a BCI user learning to control a cursor and a stroke patient recovering.
On this page12 min
A spikeSpike Shorthand for an action potential as seen by an electrode, a brief blip about a millisecond wide. Related: Action potentialAction potential The brief, all-or-nothing voltage spike a neuron fires, about a millisecond long and about 100 millivolts tall across its membrane. , Spike sortingSpike sorting Deciding which spikes on an electrode came from which neuron, by clustering their waveform shapes. , Extracellular recordingExtracellular recording Recording with an electrode near neurons rather than inside one; you see small, fast blips from nearby cells rather than the full membrane swing. . Glossary entry arriving at the end of an axon opens calcium channels, vesicles of neurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. Related: SynapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell.. Glossary entry fuse with the membrane, the transmitter diffuses across a 20-nanometre gap and opens channels on the next cell, and that cell’s membrane potentialMembrane potential The voltage across a cell's membrane, about −70 millivolts at rest, set by ion concentrations and which channels are open. Related: Resting potentialResting potential The steady membrane voltage of a neuron that is not firing, typically −60 to −70 millivolts. , Action potentialAction potential The brief, all-or-nothing voltage spike a neuron fires, about a millisecond long and about 100 millivolts tall across its membrane. , Ion channelIon channel A protein pore in the membrane that lets specific ions through, often only when the voltage or a chemical tells it to open. . Glossary entry moves by a fraction of a millivolt. That is a synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning., NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential.. Glossary entry. There are perhaps a hundred trillion of them in your head, and each one’s strength changes with use. The changing is plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. Related: Spike-timing-dependent plasticity (STDP)Spike-timing-dependent plasticity (STDP) A rule in which a synapse strengthens if the input spike arrives just before the output spike and weakens if it arrives just after., SynapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell.. Glossary entry, it is the physical basis of learning, and it is also the reason a person can learn to drive a cursor with a decoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry that was fit badly.
Excitation and inhibition
Glutamate is the main excitatory transmitter: it opens channels that let sodium in and depolarize the next cell by a millivolt or less per synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry. GABA is the main inhibitory one: it opens chloride channels that hold the cell near rest. A cortical pyramidal neuron receives tens of thousands of synapsesSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry, roughly 80 percent excitatory, and it fires when enough excitatory inputs arrive close together in time and space to overcome the leak, the inhibition, and the threshold. Cortex is a balance: excitation and inhibition track each other closely, and nearly every network rhythm in the next explainer comes from the interplay.
The coincidence detector
One glutamate receptor, the NMDA receptor, only passes current when the transmitter is present and the membrane is already depolarized (a magnesium ion blocks it at rest and is expelled by depolarization). So it opens when the presynaptic neuron fired and the postsynaptic neuron was active at the same time. It passes calcium, and calcium is the signal that changes the synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry. This one molecule implements Hebb’s rule from 1949: cells that fire together wire together.
Long-term potentiation and depression
A brief high-frequency burst of input to a synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry can double its strength for hours, days, or longer: long-term potentiation, discovered in the hippocampus in 1973 and found nearly everywhere since. Low-frequency input weakens it: long-term depression. The mechanisms involve inserting or removing receptors from the postsynaptic membrane and, over longer times, growing or shrinking the synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry itself. Spike-timing-dependent plasticitySpike-timing-dependent plasticity (STDP) A rule in which a synapse strengthens if the input spike arrives just before the output spike and weakens if it arrives just after. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning.. Glossary entry is the temporal version: if the input spikeSpike Shorthand for an action potential as seen by an electrode, a brief blip about a millisecond wide. Related: Action potentialAction potential The brief, all-or-nothing voltage spike a neuron fires, about a millisecond long and about 100 millivolts tall across its membrane. , Spike sortingSpike sorting Deciding which spikes on an electrode came from which neuron, by clustering their waveform shapes. , Extracellular recordingExtracellular recording Recording with an electrode near neurons rather than inside one; you see small, fast blips from nearby cells rather than the full membrane swing. . Glossary entry arrives a few milliseconds before the output spikeSpike Shorthand for an action potential as seen by an electrode, a brief blip about a millisecond wide. Related: Action potentialAction potential The brief, all-or-nothing voltage spike a neuron fires, about a millisecond long and about 100 millivolts tall across its membrane. , Spike sortingSpike sorting Deciding which spikes on an electrode came from which neuron, by clustering their waveform shapes. , Extracellular recordingExtracellular recording Recording with an electrode near neurons rather than inside one; you see small, fast blips from nearby cells rather than the full membrane swing. . Glossary entry, the synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry strengthens; a few milliseconds after, it weakens. Causality gets rewarded.
A BCI decoder is fit once and then left fixed for weeks while a person practices with it daily. The decoder is imperfect. What happens to performance?
Improves, often a lot. Studies in monkeys and humans show that with a fixed decoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry, the recorded neurons’ tuning shifts over days toward what the decoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry rewards, and performance climbs. The brain treats the decoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry as a new limb and learns it. This is plasticity in service of an engineering shortcut, and it is why the field talks about co-adaptation: a learning user and a learning decoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry, ideally not fighting.
Homeostasis
If potentiation ran unchecked, every synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry would saturate. Neurons scale all their synapsesSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry up or down to keep their average firing in a working range, over hours to days. This homeostatic plasticity is why a network can learn without exploding and why, after a sensory loss, the deprived cortex becomes more excitable and takes on new inputs, which is the basis of sensory substitution and of the cross-modal reorganization seen in blind and deaf people.
Why an engineer needs this
Three reasons. Learning to use a device. Cochlear implantCochlear implant The most successful neural prosthesis: an electrode array in the inner ear that stimulates the auditory nerve in up to 22 bands. Related: Vocoder (noise vocoder)Vocoder (noise vocoder) A simulation of what a cochlear implant delivers: the loudness envelope of each frequency band, applied to noise in that band. . Glossary entry users take months to a year to reach their best speech understanding; the implant does not change, the auditory cortex does. Every prosthesis and every BCIBrain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. Related: DecoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. , Closed loopClosed loop A system in which the output feeds back to influence the input, such as a user adjusting their brain activity while watching the cursor it controls. . Glossary entry depends on the user’s plasticity, and the rate of learning is part of the design. Rehabilitation. StrokeStroke Loss of blood supply to part of the brain; rehabilitation after it is the largest clinical use of neurotechnology today. Glossary entry recovery is plasticity: undamaged cortex taking over functions. Rehabilitation technology, including BCI-driven robotics and vagus nerve stimulation paired with therapy, works by promoting it, and the pairing timing matters for exactly the STDPSpike-timing-dependent plasticity (STDP) A rule in which a synapse strengthens if the input spike arrives just before the output spike and weakens if it arrives just after. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. . Glossary entry reasons above. Neuromodulation mechanisms. Whether deep brain stimulation works by silencing, by driving, or by inducing plasticity is still argued; the answer decides how to program it.
Deep dive Neuromodulators and the third factor 3 min
Dopamine, acetylcholine, noradrenaline, and serotonin are released broadly and change how plastic synapsesSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry are, rather than carrying specific signals. A synapseSynapse The junction where one neuron signals to another, usually by releasing a chemical that opens channels on the next cell. Related: Synaptic plasticitySynaptic plasticity The strengthening or weakening of synapses with use, the physical basis of learning. , NeurotransmitterNeurotransmitter A chemical released at a synapse that changes the next neuron's membrane potential. . Glossary entry that would not change on its own will potentiate if dopamine arrives shortly after, which is how reward teaches: three-factor learning, with the third factor saying “that was worth remembering.” Vagus nerve stimulation paired with rehabilitation exploits this by triggering noradrenaline and acetylcholine release at the moment of a movement, and it was approved for strokeStroke Loss of blood supply to part of the brain; rehabilitation after it is the largest clinical use of neurotechnology today. Glossary entry rehabilitation on that basis.
Deep dive Plasticity and the foreign body response 2 min
An implanted array records fewer neurons each year as scar tissue grows and neurons near the electrodesElectrode The conductor that turns ion currents in tissue into electron currents in a wire; its chemistry and contact quality set the noise you live with. Related: Silver/silver-chloride (Ag/AgCl)Silver/silver-chloride (Ag/AgCl) The standard electrode material for biopotentials, because its chemistry produces a stable, low-noise, low-drift interface with salty gel. , Electrode impedanceElectrode impedance How hard it is to push current through the skin-electrode contact, typically 5 to 50 kilohms with gel and megohms dry, higher at low frequencies. , Half-cell potentialHalf-cell potential The DC voltage that appears wherever a metal meets an electrolyte; two electrodes with different half-cell potentials produce an offset that can swamp the signal. . Glossary entry die or retreat. Meanwhile the surviving neurons’ tuning drifts. DecodersDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. Related: ClassifierClassifier An algorithm that assigns each trial a label, such as left hand or right hand, after being trained on labelled examples. , Kalman filterKalman filter An estimator that blends a prediction from a motion model with a noisy measurement, weighting each by how much it trusts it; the decoder behind most intracortical cursor control. , Brain-computer interface (BCI)Brain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. . Glossary entry that were fit to a stable population must be refit, and the user re-learns. Whether the drift is the tissue, the electrodesElectrode The conductor that turns ion currents in tissue into electron currents in a wire; its chemistry and contact quality set the noise you live with. Related: Silver/silver-chloride (Ag/AgCl)Silver/silver-chloride (Ag/AgCl) The standard electrode material for biopotentials, because its chemistry produces a stable, low-noise, low-drift interface with salty gel. , Electrode impedanceElectrode impedance How hard it is to push current through the skin-electrode contact, typically 5 to 50 kilohms with gel and megohms dry, higher at low frequencies. , Half-cell potentialHalf-cell potential The DC voltage that appears wherever a metal meets an electrolyte; two electrodes with different half-cell potentials produce an offset that can swamp the signal. . Glossary entry, or the brain’s own plasticity is an open question that matters enormously for chronic BCIsBrain-computer interface (BCI) A system that turns measured brain activity into control of something outside the body, from a cursor to a wheelchair to a speech synthesizer. Related: DecoderDecoder The algorithm that maps neural signals to intended actions, such as a classifier or a Kalman filter. , Closed loopClosed loop A system in which the output feeds back to influence the input, such as a user adjusting their brain activity while watching the cursor it controls. . Glossary entry; Phase 6 returns to it.
Explain what this page was about to your roommate in three sentences. No jargon they would not know.
We pass a message when calcium opens pouches that spill chemical across a 20 nanometer gap and shift the next cell by less than a millivolt, with about 80 percent of inputs pushing toward firing and the rest holding back. We strengthen the link when the input lands a few milliseconds before the output fires and weaken it when the order flips, and a short fast burst can double strength for hours or longer. We rely on this change when a person learns a fixed cursor decoder over days and when cochlear users gain speech understanding over months to a year while the device stays the same.
Yours does not have to match. Check that the three ideas are there.