Astrocyte Modulation of Hippocampus-Dependent Fear Learning (2015)

Undergraduate: Daniel Barrus

Faculty Advisor: Don Lysle
Department: Psychology & Neuroscience

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Pro-inflammatory immune signaling has been implicated in the onset of Post-Traumatic Stress Disorder (PTSD). Additionally, preclinical rodent findings suggest a role of pro-inflammatory cytokine release by hippocampal astrocytes in Stress-Enhanced Fear Learning (SEFL), an animal model of PTSD in which animals are exposed to a severe stressor (Context A) and subsequently exposed to a mild stressor in a distinct context (Context B). However, little is known about the precise role of hippocampal astrocytes in the brain¿¿¿s fear circuitry. We utilized Designer Receptors Exclusively Activated by Design Drugs (DREADDs) in a modified version of the SEFL paradigm in order to isolate the contribution of Gq-pathway cytokine signaling in the hippocampus to SEFL induction. Gq-DREADD technology enables the selective stimulation of Gq-pathway G protein-coupled receptors (Gq-GPCRs), which allowed us to pharmacologically induce hippocampal astrocyte activation without the use of a severe stressor (Context A of SEFL). As such, we were able to test the response of pharmacologically activated hippocampal astrocytes to a mild stressor (Context B of SEFL) in the absence of exposure to Context A. The pharmacological stimulation of the Gq-signaling pathway in the hippocampus prior to exposure to Context B resulted in a strong behavioral fear response that was resistant to extinction. This finding suggests that pro-inflammatory immune signaling in the hippocampus is critical to the induction of SEFL.