Date of Graduation

7-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Physics (PhD)

Degree Level

Graduate

Department

Physics

Advisor/Mentor

Shew, Woodrow L.

Committee Member

Kumar, Pradeep

Second Committee Member

Westerman, Erica L.

Keywords

Rett syndrome (RTT); Excitatory neurons; Inhibitory neurons; membrane; cortical processing; brain function

Abstract

Our brain consists of billions of neurons, properly coordinating to process information and realize brain functions. Among them, there are two types of neurons: excitatory neurons and inhibitory neurons. The firing of excitatory neurons increases the membrane potential of downstream neurons, and thus excites other neurons to fire. The firing of inhibitory neurons, in contrast, decreases the membrane potential of downstream neurons, and thus inhibits other neurons to fire. The interplay of excitatory and inhibitory neurons shape the spiking activity in the population. Thus, the `balance of excitation and inhibition' plays an important role in cortical processing and brain functions. An imbalance towards either excitation or inhibition leads to dysfunctional circuit mechanisms, and is related to many brain disorders. Here, we explore the influence of the balance of excitation and inhibition on cortical states and a devastating neurodevelopmental disorder - Rett syndrome (RTT).In Chapter 1, we built a family of models where varying the ratio of inhibitory synaptic strength relative to excitatory synaptic strength tunes the network dynamics to two possible cortical states - criticality and asynchronous dynamics. And our work shows that the two distinct and competing scenarios can be generated in the same neural system, when the excitation and inhibition are properly balanced. In Chapter 2, we studied how the RTT-related imbalance of excitation and inhibition influences cortical dynamics and motor function in freely behaving rats by comparing normal rats with a transgenic rat model of RTT. Our results suggest that excessive inhibition in RTT gives rise to an excessive synchrony in primary motor cortex, which is related to stereotyped intracortical and cortex-body interactions and less complexity in movement.

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