Title

Developmental Participation of VIP Interneurons in Cortical Dynamics

Date of Award

Fall 10-1-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdepartmental Neuroscience Program

First Advisor

Higley, Michael

Abstract

In the mammalian cerebral cortex, local and long-range synaptic connections are believed to relay information related a diverse array of cognitive, emotional, and physiological functions to influence the computations performed by single neurons. While the anatomical connectivity of a single neuron is static on short timescales, its functional involvement in distributed networks may fluctuate rapidly to subserve moment-to-moment changes in behavior. A sparse class of interneurons that express vasoactive intestinal polypeptide (VIP) has been hypothesized to mediate these fluctuations by modulating the gain of cortical micro-circuits in response to neuromodulatory and long-range cortico-cortical inputs. To test this hypothesis, we developed a method to directly measure the functional coupling of individual neurons with distal cortical regions by simultaneous two-photon cellular-resolution and mesoscopic areal-resolution calcium imaging. We used this method to measure how large-scale cortical activity patterns influence the activity of VIP interneurons and their neighboring excitatory neurons, and found that both VIP interneurons and excitatory neurons participate in cortex-wide functional networks that change as a function of behavioral state. Further, we have gained preliminary evidence that the participation of neurons in these networks emerges early in juvenile development and requires both cholinergic and glutamatergic input to VIP interneurons. Efforts are ongoing to better understand the features of large-scale activity patterns that most influence the activity of individual neurons and the mechanisms that couple individual neurons to distributed cortical networks.

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