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Cerebral cortex

Classifying inhibitory synapses in the cortex: beyond cell types

Nature Reviews Neuroscience volume 24, page 269 (2023)Cite this article

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About 20% of cortical neurons in the mammalian brain are inhibitory GABAergic interneurons that balance the level of excitation within cortical networks and are thus critical for information processing. Although it has long been known that cortical GABAergic neurons have diverse morphologies, classifying them into distinct types (or subclasses) only became possible with recent advances in the tools available to measure their physiological and molecular properties. Even within neurons of the same type, however, it became clear that each of the numerous synapses formed by an individual neuron with its postsynaptic partners can have different physiological and morphological properties. This prompted researchers to move beyond cell types and instead examine the functional classification of GABAergic synapses.

In 2000, in one of the pioneering studies in this field, Gupta, Wang and Markram set out to explore the properties of the synapses formed by distinct types of cortical GABAergic neurons in slices of rat somatosensory cortex. They performed 800 quadruple patch-clamp recordings, in each of which both GABAergic and pyramidal neurons were patched simultaneously, combined with post hoc histology to reconstruct the 3D structure of the recorded neurons. Using this approach, the authors measured the temporal dynamics of inhibitory synaptic transmission from morphologically and physiologically defined GABAergic neurons to distinct types of postsynaptic neurons. They assessed 3,000 potential GABAergic connections, from which they identified three types of GABAergic synapses. These were classified by testing the recovery of the postsynaptic response to a single evoked action potential (AP) following the delivery (500 ms earlier) of a short train of APs in the GABAergic neuron: in one set of synapses the test response was facilitated (when compared to the first response to the AP train), in another it was depressed and in the third it was unchanged.

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References

Original article

  • Gupta, A., Wang, Y. & Markram, H. Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287, 273–278 (2000)

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  1. Department of Biological Sciences, KAIST, Daejeon, Republic of Korea

    Seung-Hee Lee

  2. Center for Synaptic Brain Dysfunctions, IBS, Daejeon, Republic of Korea

    Seung-Hee Lee

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  1. Seung-Hee Lee
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Correspondence to Seung-Hee Lee.

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Lee, SH. Classifying inhibitory synapses in the cortex: beyond cell types. Nat Rev Neurosci 24, 269 (2023). https://doi.org/10.1038/s41583-023-00683-z

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