The Role Of ERβ In Sleep And Circadian Regulation

Letters & Science (College of) / Psychological & Brain Sciences

Project Description

This project aims to determine the role of estradiol and estrogen receptors in stress-induced sleep impairments and related behavioral deficits, and to identify the underlying neural circuits involved. In Aim 1, male and female mice will undergo gonadectomy or sham surgery combined with implantation of wireless EEG/EMG telemetry for simultaneous sleep and local field potential recordings from prefrontal cortex (PFC)–BLA circuits. Following baseline assessments, mice will be exposed to acute footshock stress, and the effects of selective ERβ agonist, as well as 17β-estradiol, on preventing sleep, neuronal, and behavioral impairments will be evaluated. In Aim 2, wild-type mice will receive AAV-mediated Cre-dependent excitatory or inhibitory DREADDs in PFC–NAc or PFC–BLA projections, combined with retro-Cre in target regions, enabling projection-specific modulation. After viral expression and surgical preparation, baseline sleep, neuronal activity, and behavioral data will be collected, followed by stress exposure with either CNO or vehicle treatment. Activating these projections is expected to prevent stress-induced impairments, while inhibition in intact mice is predicted to mimic hypogonadal deficits. Post-experiment, brains will be analyzed to confirm electrode and viral targeting. This integrative approach combines hormonal manipulation, chemogenetic circuit modulation, and in vivo electrophysiology to elucidate hormone–circuit interactions in sleep and stress-related behavioral regulation. 

Tasks and Responsibilites

The student will play an active role in all stages of the experimental workflow. They will be responsible for conducting behavioral experiments, including operant conditioning training, ensuring animals reach stable performance levels, and performing subsequent behavioral testing following experimental manipulations. They will carry out stress exposure protocols in accordance with established procedures and maintain accurate, detailed records of behavioral performance. The student will assist in surgical procedures, including preparation for and support during gonadectomy surgeries, gaining experience in aseptic techniques and perioperative care. In addition, the student will contribute to the collection and analysis of sleep data acquired through EEG/EMG telemetry, including scoring sleep/wake states and performing basic signal analysis under supervision. They will also participate in organizing and analyzing data for both behavioral and electrophysiological outcomes, generating summary figures, and assisting in the interpretation of results for presentations and publications. Throughout the project, the student will be expected to follow all animal care and use protocols, adhere to biosafety and ethical guidelines, and participate in regular lab meetings to discuss progress, troubleshoot experimental issues, and contribute to experimental planning. This hands-on involvement will provide comprehensive training in behavioral neuroscience, surgical assistance, and electrophysiological data analysis.

Desired Qualifications

None Listed.