Diverse behavioral representation by neocortical PV interneuron dynamics converges between SI and V1

More, Alexander

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Year:: 2023
Contributor:: More, Alexander (creator); Connors, Barry (Reader); Moore, Christopher (Advisor); Berson, David (Reader); Crandall, Shane (Reader); Brown University. Department of Neuroscience (sponsor)
Genre:: theses
Subject:: Fast-spiking interneurons; Neocortex; Inhibition
Extent:: XI, 154 p.

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Abstract:: The Neocortex is a complex brain structure that represents the outside world, optimizes behavior, and provides associations based on prior learning. The Neocortex achieves these computations through flexible neural representations created by many cell types and mechanisms. Local inhibitory interneurons are leading contributors, acting through inhibition to shape excitatory activity. Parvalbumin-positive interneurons (PV) are the most numerous interneurons in Neocortex and exert powerful local control on signal relay by neighboring pyramidal cell ensembles. Despite intensive study, substantial debate exists as to how PV contribute to active processing, with opposing views regarding the value of their increased versus decreased activity. In this thesis, I describe the discovery of two distinct PV cell ensembles that show increased and decreased activity that predicts success in sensory detection, a motif shared between Primary Somatosensory (SI) and Visual Neocortex (V1). Specifically, the “Hit” PV ensemble fires more on successfully perceived trials, while the “Miss” ensemble shows decreased activity. Our modeling suggests that Hit PV receive contextual signals that they translate into optimal signal relay and improved perception. Specifically, the model predicts that increased Hit PV firing suppresses Miss PV, in turn disinhibiting pyramidal neurons and amplifying sensory relay. Further, discoveries I made in V1 support the view that the Hit PV ensemble is key to contextual behavioral control. First, I found that Hit PV predominate in Layer II versus Layer III, consistent with enhanced top-down input. Second, I discovered a substantial population of non-sensory Hit PV, attuned to context and not the outside world, a feature not found amongst Miss PV. To study PV selectively, I employed two-photon calcium imaging combined with a threshold-level sensory detection task. To selectively control activity in such genetically-defined cell classes, I helped develop a unique optogenetic-chemogenetic combined molecular control tool, Bioluminescent-Optogenetics (BL-OG). I further helped develop tools for photo-switching BL-OG efficacy ‘on’ with 2-photon light. This new tool should provide a direct method for selectively controlling specific, functionally-defined ensembles, such as those I discovered in V1. These results demonstrate a common computational architecture exists among PV cells across Primary Sensory Neocortical areas, and show direct evidence for functional specialization of Layer II versus Layer III.
Notes:: Thesis (Ph. D.)--Brown University, 2023

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Citation

More, Alexander, "Diverse behavioral representation by neocortical PV interneuron dynamics converges between SI and V1" (2023). Neuroscience Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:5rtp8se2/

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Neuroscience Theses and Dissertations

Theses and Dissertations for the Neuroscience department.
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