Authors: Justin Webb
Mentors: Jeffrey Edwards
Insitution: Brigham Young University
Understanding the mechanisms underlying depotentiation in the context of previously induced long-term potentiation (LTP) is crucial for unraveling the processes of memory consolidation and forgetting. Our research is focused on synaptic plasticity in the hippocampus, the primary brain region responsible for mediating learning and memory. Using electrophysiology and neuropharmacological techniques, our goal is to elucidate the cellular mechanisms behind depotentiation, a reversal of the increase in postsynaptic response and overall synaptic strength characteristic of LTP. By doing this research, we hope to both fill existing gaps and resolve conflicting views about the processes and receptors involved in depotentiation. Experiments were performed on hippocampal brain slices of young mice. We induced LTP in hippocampal CA1 neurons using high-frequency electrical stimulation, and then elicited depotentiation in the same neurons via low-frequency electrical stimulation. This creates a cellular event analogous to learning and subsequently forgetting a new memory trace. Our preliminary findings show that depotentiation still occurs in the presence of MPEP, a metabotropic glutamate receptor (mGluR5) antagonist, suggesting that the depotentiation mechanism is independent of mGluR5. Additionally, because female rodent models have largely been ignored in prior electrophysiology experiments involving LTP and depotentiation, we investigated and observed gender-related differences, which show female mice exhibiting more pronounced depotentiation than their male counterparts. Building on these findings, our research will continue to identify gender-related differences in both juvenile and adolescent mice, as well as explore the role of NMDA receptors on depotentiation. We will also extend the temporal gap between LTP induction and depotentiation to explore the impact of early-phase versus late-phase LTP on subsequent depotentiation. This research aims to shed light on the intricate mechanisms of synaptic plasticity and its implications for learning, memory, and potential therapeutic modulation of these processes in the context of conditions like Alzheimer's disease, post-traumatic stress disorder (PTSD), and other disorders of learning and memory.