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The plasticitome of cortical interneurons

Nature Reviews Neuroscience volume 24, pages 80–97 (2023)Cite this article

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Abstract

Hebb postulated that, to store information in the brain, assemblies of excitatory neurons coding for a percept are bound together via associative long-term synaptic plasticity. In this view, it is unclear what role, if any, is carried out by inhibitory interneurons. Indeed, some have argued that inhibitory interneurons are not plastic. Yet numerous recent studies have demonstrated that, similar to excitatory neurons, inhibitory interneurons also undergo long-term plasticity. Here, we discuss the many diverse forms of long-term plasticity that are found at inputs to and outputs from several types of cortical inhibitory interneuron, including their plasticity of intrinsic excitability and their homeostatic plasticity. We explain key plasticity terminology, highlight key interneuron plasticity mechanisms, extract overarching principles and point out implications for healthy brain functionality as well as for neuropathology. We introduce the concept of the plasticitome — the synaptic plasticity counterpart to the genome or the connectome — as well as nomenclature and definitions for dealing with this rich diversity of plasticity. We argue that the great diversity of interneuron plasticity rules is best understood at the circuit level, for example as a way of elucidating how the credit-assignment problem is solved in deep biological neural networks.

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Fig. 1: Cellular learning while normalizing synaptic weights by combining homosynaptic and heterosynaptic plasticity.
Fig. 2: One, two or more factors can determine IN plasticity.
Fig. 3: Opposing forms of IN intrinsic plasticity.
Fig. 4: The plasticitome.

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Acknowledgements

The authors thank A. Watt, W. Gerstner, R. P. Costa, A. Suvrathan, C. Bourque, H. Wong, O. Camiré, S. Rannio and Sjöström laboratory members for help and useful discussions. P.J.S. was supported by Fonds de Recherche du Québec - Santé (FRQS) CB 254033 and Natural Sciences and Engineering Research Council of Canada (NSERC) DG 2017-04730. A.R.M. was supported by doctoral awards from FRQS (287520) and Healthy Brains for Healthy Lives (HBHL). C.Y.C.C. was in receipt of doctoral awards NSERC D3-534171-2019 and Fonds de Recherche du Québec - Nature et technologies (FRQNT) 275075. A.W. was a recipient of HBHL, Integrated Program in Neuroscience(IPN) and Quebec Bio-Imaging Network (QBIN) fellowships. N.C. is an NSERC USRA (552184-2020) and FRQNT BRPC Supplement (298265) recipient. M.H. was funded by Canada Summer Jobs (CSJ).

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Authors and Affiliations

  1. Centre for Research in Neuroscience, Department of Medicine, The Research Institute of the McGill University Health Centre, Montréal, Québec, Canada

    Amanda R. McFarlan, Christina Y. C. Chou, Airi Watanabe, Nicole Cherepacha, Maria Haddad, Hannah Owens & P. Jesper Sjöström

  2. Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada

    Amanda R. McFarlan, Christina Y. C. Chou, Airi Watanabe, Maria Haddad & Hannah Owens

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Contributions

All authors researched data for the article, contributed substantially to discussion of the content and wrote the article. A.R.M, C.Y.C.C, A.W. and P.J.S. reviewed and edited the manuscript before submission.

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Correspondence to P. Jesper Sjöström.

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Glossary

Anti-Hebbian

A rule that disobeys Hebb’s postulate, such as synaptic strengthening resulting from asynchronous firing in connected cells or, conversely, coincident firing eliciting synaptic weakening.

Coincidence detection

A process by which a neuron or a neuronal circuit can detect the occurrence of temporally close but spatially distributed input signals to form associations between distinct events.

Disinhibition

Reduction of inhibitory drive onto an excitatory neuron.

E → I plasticity

Plasticity at synapses from excitatory to inhibitory cells.

E/I balance

The relative contributions of excitatory and inhibitory synaptic input to an individual neuron or in a local circuit.

Excitatory postsynaptic potential (EPSP)-spike potentiation

The ability of long-term potentiation (LTP) to additionally increase the potentiated input’s capacity to drive postsynaptic spiking by altering postsynaptic excitability.

Expression of plasticity

The mechanisms that alter the strength of a synaptic connection, such as the addition or removal of neurotransmitter receptor channels postsynaptically, or changes of release probability presynaptically.

Homeostatic plasticity

The capacity of neurons to regulate their own excitability and synaptic drive slowly over many hours in the face of changes in network structure and activity.

I → E plasticity

Plasticity at synapses from inhibitory to excitatory cells, which has often been called inhibitory long-term potentiation (LTP) or inhibitory long-term depression (LTD).

Induction of plasticity

The processes that trigger the expression of long-term plasticity; typically a repeated activity pattern, but could also be chemical or pharmacological.

Miniature excitatory postsynaptic current

A depolarizing current elicited by excitatory neurotransmitters such as glutamate that promotes spiking in the postsynaptic neuron.

Miniature inhibitory postsynaptic current

A hyperpolarizing current elicited by inhibitory neurotransmitters such as GABA that reduces spiking in the postsynaptic neuron.

Negative feedback

A mechanism that acts similar to a thermostat to keep a parameter such as temperature or activity within reasonable bounds by reducing it if too high and increasing it if too low.

Positive feedback

A mechanism that achieves run-away regenerative events, such as voltage-dependent sodium channels driving action potential rise; the more they depolarize, the more they open and promote further depolarization.

Quantal amplitude

The release of one synaptic vesicle containing a stereotyped amount of neurotransmitter — a quantum — elicits a postsynaptic response of one quantal amplitude.

Reversal potential

The membrane potential at which an ion channel current reverses its sign.

Rheobase

The minimal current amplitude needed to be injected into a cell to elicit an action potential. It is a measure of membrane potential excitability.

Synapse type-specific plasticity

The activity requirements that determine plasticity depend on the synapse type, which in turn is related to the presynaptic and the postsynaptic cell types.

Theta burst stimulation

(TBS). Short bursts of stimulation at high frequency, typically 100 Hz, with the bursts themselves applied at 5–8 Hz, to mimic hippocampal theta rhythm and to achieve pre-priming disinhibition, which yields more long-term potentiation (LTP) while improving biological realism.

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McFarlan, A.R., Chou, C.Y.C., Watanabe, A. et al. The plasticitome of cortical interneurons. Nat Rev Neurosci 24, 80–97 (2023). https://doi.org/10.1038/s41583-022-00663-9

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