Author ORCID Identifier

0000-0003-0701-3528

Date of Graduation

5-2021

Document Type

Dissertation (PhD)

Program Affiliation

Neuroscience

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Valentin Dragoi, PhD

Committee Member

Ruth Heidelberger, MD, PhD

Committee Member

Xaq Pitkow, PhD

Committee Member

Matthew McGinley, PhD

Committee Member

Fabricio Do Monte, DVM, PhD

Committee Member

Louise McCullough, MD, PhD

Abstract

Cortical columns represent the elementary functional and computational module of the neocortex. Although much is known about its laminar structure and synaptic connectivity, how patterns of spiking activity propagate within columnar circuits when the state of the brain changes remains poorly understood. We used multi-electrode laminar arrays to reveal that brain state modulates the propagation of neural activity across the layers of early and mid-level visual cortex (areas V1 and V4). We found a high prevalence of neuronal synchrony (vigorous (On) and weak (Off) spiking) in rest but low prevalence of synchrony during wakefulness. We next tested whether propagation of synchrony across cortical circuits is state dependent. By optogenetically inducing On and Off state transitions within a single cortical layer during wakefulness, we found that synchronized neural activity propagates to other layers only weakly, and the extent of spread is inversely related to arousal level. In contrast, during rest, optogenetically-induced population activity vigorously propagates throughout the entire cortical column even when neurons are in a desynchronized wake-like state prior to optogenetic stimulation. The influence of the global brain state on the propagation of spiking activity across laminar circuits was explained by changes in the coupling between neurons, where neurons were weakly coupled during wakefulness but strongly coupled during rest. The state-dependent propagation of synchronous activity revealed here could constitute a general principle of signal transmission within the sensory cortex.

In addition to understanding how neuronal coupling modulates synchrony propagation in wakefulness and rest, we probed the functional significance of synchrony by studying the influence of NREM sleep (where high levels of synchrony are observed) on coding and cognitive performance. We used non-human primates to record the changes in activity of single neurons, neuronal populations, and local field potentials in V4 that occur before, during, and after NREM sleep. To test the cognitive effects of naps, monkeys performed a visual discrimination task before and after taking a nap. We found that high levels of synchrony during NREM sleep drive the brain to be further asynchronous after sleep compared to before sleep. Thus, synchrony in NREM sleep improves behavior by modulating population level dynamics., which we mechanistically tested by performing local microstimulation to induce synchrony in V4 of awake animals. Local microstimulation in V4 replicated the changes in neuronal coding and behavioral performance observed after sleep. We uncovered how synchrony in sleep influences neuronal coding changes in single neurons and in neural ensembles that lead to sleep dependent improvement in cognitive performance. Overall, these findings expand our understanding of the functional significance of synchrony, the neurobiology of sleep, and the neuronal coding that drives perception.

Keywords

synchrony; coding; NREM sleep; primate optogenetics; microstimulation; signal propagation; visual cortex

Available for download on Thursday, May 05, 2022

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