Gord Fishell

Gord Fishell, Ph.D.

Professor of Neurobiology, Harvard Medical School

The Diverse Landscape of Inhibitory Interneurons

A century ago Ramon y Cajal dubbed the local short axon cells of the brain, the inhibitory interneurons, “the butterflies of the soul”. With characteristic insight, he inferred that these populations, which possess such enormous morphological diversity, would ultimately prove to have an equally impressive breadth of functional attributes. Recent studies have born out this prediction and shown that inhibitory interneurons are much more than simple gatekeepers of excitation. Depending on which interneuron subtype is recruited they are able to refine or unite brain activity in a startling multitude of ways.

The Fishell laboratory is focused on how this diversity is created. Understanding how this is accomplished during development remains one of the most daunting problems in biology. In particular, we wish to understand not only how the vast variety of inhibitory interneuron subtypes are generated but how they subsequently integrate into the bewildering array of neural circuits that are embedded in different brain structures.

Our working hypothesis is that this is achieved through a two-step process. The first involves genetic programs that in accordance with their birthdate create a finite number of cardinal interneuron subtypes. Following the tiling of these newly born cardinal subtypes across different brain structures, local cues act to create the definitive subtypes characteristic of the distinct cortical and subcortical areas. Importantly, as we have explored the molecular control of these events, it has become clear that perturbation of this process can result in a variety of brain dysfunctions including autism spectrum disorder, intellectual disability and schizophrenia. A new and growing interest in the laboratory is therefore aimed at seeing if better understanding of these developmental events can lead to the development of new treatments for these disorders.

Publications View
An anatomical and physiological basis for flexible coincidence detection in the auditory system.
Authors: Authors: Kreeger LJ, Honnuraiah S, Maeker S, Shea S, Fishell G, Goodrich L.
Elife
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Divergent opioid-mediated suppression of inhibition between hippocampus and neocortex across species and development.
Authors: Authors: Caccavano AP, Vlachos A, McLean N, Kimmel S, Kim JH, Vargish G, Mahadevan V, Hewitt L, Rossi AM, Spineux I, Wu SJ, Furlanis E, Dai M, Leyva Garcia B, Wang Y, Chittajallu R, London E, Yuan X, Hunt S, Abebe D, Eldridge MAG, Cummins AC, Hines BE, Plotnikova A, Mohanty A, Averbeck BB, Zaghloul KA, Dimidschstein J, Fishell G, Pelkey KA, McBain CJ.
Neuron
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Differential behavioral engagement of inhibitory interneuron subtypes in the zebra finch brain.
Authors: Authors: Hozhabri E, Corredera Asensio A, Elmaleh M, Kim JW, Phillips MB, Frazel PW, Dimidschstein J, Fishell G, Long MA.
Neuron
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Pyramidal neurons proportionately alter the identity and survival of specific cortical interneuron subtypes.
Authors: Authors: Wu SJ, Dai M, Yang SP, McCann C, Qiu Y, Marrero GJ, Stogsdill JA, Di Bella DJ, Xu Q, Farhi SL, Macosko EZ, Che F, Fishell G.
Res Sq
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Interneuron Diversity: How Form Becomes Function.
Authors: Authors: De Marco García NV, Fishell G.
Cold Spring Harb Perspect Biol
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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.
Authors: Authors: Furlanis E, Dai M, Leyva Garcia B, Vergara J, Pereira A, Pelkey K, Tran T, Gorissen BL, Vlachos A, Hairston A, Huang S, Dwivedi D, Du S, Wills S, McMahon J, Lee AT, Chang EF, Razzaq T, Qazi A, Vargish G, Yuan X, Caccavano A, Hunt S, Chittajallu R, McLean N, Hewit L, Paranzino E, Rice H, Cummins AC, Plotnikova A, Mohanty A, Tangen AC, Shin JH, Azadi R, Eldridge MAG, Alvarez VA, Averbeck BB, Alyahyay M, Reyes Vallejo T, Soheib M, Vattino LG, MacGregor CP, Banks E, Olah VJ, Naskar S, Hill S, Liebergall S, Badiani R, Hyde L, Xu Q, Allaway KC, Goldberg EM, Nowakowski TJ, Lee S, Takesian AE, Ibrahim LA, Iqbal A, McBain CJ, Dimidschstein J, Fishell G, Wang Y.
bioRxiv
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Pyramidal neurons proportionately alter the identity and survival of specific cortical interneuron subtypes.
Authors: Authors: Wu SJ, Dai M, Yang SP, McCann C, Qiu Y, Marrero GJ, Stogsdill JA, Di Bella DJ, Xu Q, Farhi SL, Macosko EZ, Chen F, Fishell G.
bioRxiv
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Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity.
Authors: Authors: Huang S, Rizzo D, Wu SJ, Xu Q, Ziane L, Alghamdi N, Stafford DA, Daigle TL, Tasic B, Zeng H, Ibrahim LA, Fishell G.
Res Sq
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Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development.
Authors:
Nat Commun
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Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity.
Authors:
bioRxiv
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