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Shaping long-range functional connectivity through prefrontal interneuron plasticity

Neuropsychopharmacology (2022)Cite this article

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Undergirding the study of these dynamic interactions are efforts to map the structural and functional connections between long-range inputs and mPFC interneurons. Indeed, work using trans-synaptic viral tracing, retrograde labelling, optogenetic stimulation, and whole-cell electrophysiology has revealed previously unappreciated specificity in the synaptic targeting and modulation of mPFC interneurons by inputs originating from disparate and intermingled neuronal populations (e.g., [3,4,5,6]). In one striking study, Sanchez-Bellot and colleagues [4] showed that a subset of projection neurons in superficial vHPC preferentially synapses onto diverse mPFC interneurons, whereas a subset in deeper vHPC preferentially targets pyramidal neurons and fast-spiking interneurons. This dissociable connectivity seems to underlie functional specificity, as activation of these parallel pathways promoted exploration and avoidance, respectively.

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Fig. 1: Synaptic plasticity between mPFC interneurons and their long-range afferents is positioned to exert dynamic control of cognition-supporting functional connectivity.

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Funding

Support for this work is provided by the NINDS Intramural Research Program (ZIA NS003168-04).

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Authors and Affiliations

  1. Integrative Neuroscience Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA

    David A. Kupferschmidt & Joshua A. Gordon

  2. National Institute of Mental Health, Bethesda, MD, USA

    Joshua A. Gordon

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  1. David A. Kupferschmidt
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  2. Joshua A. Gordon
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JAG and DAK conducted a literature review, planned and edited the manuscript. DAK wrote the first draft of the manuscript.

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Correspondence to David A. Kupferschmidt.

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Kupferschmidt, D.A., Gordon, J.A. Shaping long-range functional connectivity through prefrontal interneuron plasticity. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01395-1

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  • DOI: https://doi.org/10.1038/s41386-022-01395-1

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