Project Description
This project aims to define how estrogen receptor β (ERβ) regulation of the oxytocin (OT) system contributes to stress-induced reward impairments, focusing on the paraventricular nucleus (PVN)–basolateral amygdala (BLA)–nucleus accumbens (NAc) circuit. We hypothesize that hypogonadism increases methylation of the OT gene promoter in the PVN, reducing OT transcription and release to the BLA, which in turn decreases ERβ BLA–NAc circuit activity and drives social reward deficits. In Aim 1, we will establish the role of the oxytocinergic system in reward processing under hypogonadal conditions. Gonadectomized and sham-operated mice will undergo mild stress (subthreshold social defeat) followed by behavioral testing (social interaction, sucrose preference, progressive ratio). We will assess OT gene methylation and use fiber photometry with OT biosensors to measure PVN–BLA OT dynamics. In Aim 2, we will determine whether OTR signaling in the BLA–NAc projection is necessary for reward regulation. Using RNAscope, we will quantify OTR expression on ERβ BLA–NAc neurons, and with fiber photometry plus intra-BLA OT infusion, we will test whether OTR activation rescues circuit and behavioral deficits. This multidisciplinary behavioral, molecular, and circuit-level approach will identify hormone–neuropeptide mechanisms underlying stress vulnerability and reward processing, informing novel therapeutic strategies.
Tasks and Responsibilites
The student will be actively involved in both behavioral and circuit-level components of the project. Their primary responsibility will be running the operant conditioning experiments, including training mice to perform the task, monitoring performance, and ensuring that behavior reaches stable baselines before experimental manipulations. They will also assist in implementing stress paradigms and conducting behavioral testing to assess social interaction and reward-related measures. On the circuit side, the student will be trained to assist with fiber photometry experiments, including preparation and calibration of the recording setup, data collection during behavioral sessions, and synchronization of behavioral and neural activity data. They will participate in stereotaxic surgeries by preparing surgical equipment, assisting with animal positioning, and handling post-operative care. For data analysis, the student will learn to process and interpret fiber photometry signals using MATLAB, applying analysis pipelines to extract relevant measures and prepare figures for presentations or reports. Throughout the project, the student will maintain detailed experimental records, follow all animal care and safety protocols, and participate in lab meetings to discuss progress and troubleshoot experiments. This hands-on role will give the student experience in behavioral neuroscience, in vivo circuit monitoring, surgical assistance, and coding for data analysis.
Desired Qualifications
None Listed.