Date of Graduation

5-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Physics (PhD)

Degree Level

Graduate

Department

Physics

Advisor/Mentor

Shew, Woodrow

Committee Member

Li, Jiali

Second Committee Member

Evans, Timothy

Keywords

Rett syndrome; criticality; electrophysiological recordings

Abstract

Rett syndrome (RTT) is a rare neurological disorder, caused by disrupted function of the MECP2 gene, resulting in impaired cognitive and motor functions. Previous studies suggest that although MECP2 has important functions throughout the body, the etiological origins of RTT-related dysfunction should be sought within the brain. However, it remains a mystery how neural population dynamics are altered in the RTT brain and how these alterations relate to motor dysfunction. Previous studies using an RTT mouse model point to abnormal correlations among firing rates of neurons. Here we hypothesize that such disrupted neural activity correlation could be caused by abnormal deviation from a particular dynamical regime, called criticality. Previous experiments and theory suggest that the brain tunes itself along a continuum of states nearby criticality, ranging from synchronized to desynchronized dynamics. Such tuning may take advantage of different computational advantages and tradeoffs near criticality. Here we performed electrophysiological recordings of many single units in the striatum of WT (n=4) and RTT (n=4) awake mice. The mice were head-fixed on a computer-controlled wheel with alternating rest and forced-run periods. We used a new theory-driven data analytic technique to assess proximity to criticality in a time-resolved way. In addition, we analyzed paw coordination during running. We found that, during the forced run condition, RTT mice exhibited decreased paw coordination and tended to drag their hind paws more than the WT mice. For both WT and RTT mice, we found that the striatum is closer to criticality during rest periods than during forced run periods, we found that the WT mice were further away from criticality than the RTT. Our results suggest that in RTT mice, neural dynamics are less tunable, unable to reach the desynchronized state. If the desynchronized state is beneficial for active behaviors like our forced run condition, then the inability to reach that state may contribute to decreased motor coordination and hypoactivity in RTT mice.

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