Degree Name

Department

Neuroscience

College

Life Sciences

Defense Date

2024-03-08

Publication Date

2024-03-13

First Faculty Advisor

Jeff Edwards

First Faculty Reader

Mike Brown

Honors Coordinator

Rebekka Matheson

Keywords

Hippocampus, Plasticity, Depotentiation, Mice, Neuroscience, Sex Differences

Abstract

Synaptic plasticity of excitatory hippocampal circuits is one of the primary cellular mechanisms of learning and memory. Synaptic plasticity is also implicated in many disease states such as depression, post-traumatic stress disorder, and Alzheimer disease. Long-term potentiation (LTP) is the plastic strengthening of synapses, while long-term depression (LTD) is the weakening of synapses. Depotentiation is the process of reversing previously established long-term potentiation. Depotentiation has not been studied as thoroughly as long-term potentiation and long-term depression. We examined the role of age, metabotropic glutamate receptor 5 (mGluR5), and sex in the process of CA1 hippocampal depotentiation in young CD-1 mice using field electrophysiology. In juvenile (14-34 days, n=11), adolescent (35-59 days, n=8), and young adult mice (70-100 days, n=5), there were no significant age-related differences in CA1 hippocampal LTP or depotentiation (p>0.05). Using MPEP, an antagonist of mGluR5, we showed that hippocampal depotentiation is mGluR5-independent in juvenile mice (control n=11, MPEP n=7, p>0.05). This was also the case for adolescent mice (control n=8, MPEP n=7, p>0.05). Slices from juvenile female mice (n=6) demonstrated significantly larger (p=0.030) depotentiation compared to slices from juvenile male mice (n=4) due to increased magnitude of LTP (p=0.032). Our data on adolescent female (n=4) and male (n=4) mice is underpowered to perform statistical analysis. Our results demonstrate the importance of including female subjects in plasticity research.