Bilateral Cerebellar Stimulation Enhances Functional Recovery and Influences Cortical Coherence in a Mouse Model of Traumatic Brain Injury
cairo shetka1, Eyoel Desalegn1, Yu Liu1, Detlef Heck1
1University of Minnesota Duluth
Objective:
In a previous study, we demonstrated that bilateral optogenetic cerebellar stimulation was able to improve functional recovery in mice with traumatic brain injury (TBI). This project aims to extend these behavioral data and begin investigating the underlying electrophysiology.
Background:
TBIs constitute a major health burden and can profoundly impair daily functioning. Their sequelae are quite variable; affecting motor, cognitive, and behavioral functions. This heterogeneity, alongside limited mechanistic insight, has hindered therapeutic progress and few effective treatments exist. Emerging research in animal and human models suggests that cerebellar stimulation may benefit TBI recovery.
Design/Methods:
Baseline brain function in adult ChR2-Pcp2Cre(+) mice (5 males, 1 female) was assessed using various behavioral-cognitive tasks and exploratory homecage monitoring. The mice were then subjected to repeated closed head TBI via a CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) protocol before the installation of 2 blue light LEDs (470nm) centered on the Cerebellar Lobule Simplex, along with recording electrodes in mPFC, bilateral CA1, and M1. Half received cerebellar stimulation (CBST; 12 days, twice daily, 5Hz sinusoidal voltage, 2s on, 3s off for 20 mins) and half received no stimulation (NOST). All behavioral tasks were then repeated with concurrent recording of neuronal activity. The ultrasonic vocalizations (USVs) generated by a pilot group of 4 male mice (2 CBST, 2 NOST) in the presence of a novel female were also recorded post TBI.
Results:
CBST mice demonstrated increased exploration behavior and enhanced coherence in local field potential between recorded regions. CBST mice also vocalized at a higher rate in the presence of a female and used USVs of significantly longer duration and wider bandwidth.
Conclusions:
Our behavioral data are consistent in demonstrating cerebellar stimulation as beneficial to functional TBI recovery and USVs are a novel measure of this. Electrophysiology suggests increased functional interaction between cortical regions as a potential mechanism.
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