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ORCID

http://orcid.org/0000-0003-3749-4094

Date of Award

Spring 5-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The hippocampus is a critical brain structure for learning and memory. Neuronal inhibition within the hippocampus, performed by a wide variety of inhibitory interneuron subtypes, is required to organize and regulate the cell activity and circuit operations which underly memory formation. Despite the importance of inhibitory interneurons to the function of the hippocampus, detailed descriptions of the role of interneurons in the regulation of network activity have been limited by difficulties associated with identifying and recording from these cells using traditional electrophysiology techniques, especially in awake, behaving animals. To better investigate the function of hippocampal interneurons in awake, behaving animals, we used 2-photon calcium imaging to record from genetically identified interneurons in region CA1 of the hippocampus of mice performing a virtual reality navigation task.Animal movement is a powerful determinant in hippocampal network states, yet the mechanism through which the hippocampus is alternately engaged in distinct states during periods of locomotion or immobility are poorly understood. We investigated the role of hippocampal interneuron during different movement states using in vivo, two-photon calcium imaging in awake, behaving mice performing a virtual reality navigation task. In both somatostatin- and parvalbumin-expressing populations of interneurons, the majority of cells were active during periods of locomotion. However, small subpopulations within these interneuron groups were most active during periods of immobility. These associations between locomotor state and cell activity were stable across days and virtual environments. Anatomically, somatostatin immobility-activated neurons were distinguished by smaller somata than movement-activated neurons. These findings are consistent with a model of distinct hippocampal interneuronal microcircuits differentially activated during either movement or immobility periods. These inhibitory networks may regulate information flow in “labeled lines” within the hippocampus to process information during distinct behavioral states. Next, we investigated the role of hippocampal interneurons during learning. Inhibition, primarily mediated by interneurons, is well known to regulate network excitation and plasticity; however, the relationship between learning and inhibitory activity dynamics remains unclear. We recorded hippocampal CA1 somatostatin- and parvalbumin-expressing interneurons as mice learned a virtual reality task in new visual contexts. Interneuron activity was strongly suppressed upon initial exposure to novel environments, this suppression gradually diminished over subsequent exposures to the same, initially novel, contexts. When learning was prevented through the use of a context in which learning was impossible, activity suppression did not diminish. Interneurons displayed a high degree of stability of suppression response to multiple instances of novelty. These findings suggest that interneurons play an active role in modulating network activity during learning. Their remarkably stable functional architecture suggests that individual interneurons play specific roles during learning, perhaps by differentially regulating excitatory neuron ensembles.

Language

English (en)

Chair and Committee

Edward B. Han

Committee Members

Lawrence Snyder, Timothy Holy, Daniel Kerschensteiner,

Available for download on Sunday, May 15, 2022

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