Samuel Hauke, “Learning and Estrogen Signaling Recruits Excitatory Neurons in the Mouse Dorsal Hippocampus into a Spatial Memory Engram”
Mentor: Karyn Frick
Poster #11
Learning stimulates neuronal activity in the dorsal hippocampus (DH), resulting in contact formation and information transmission between neurons. The mechanistic changes elicited by learning are commonly referred to as synaptic plasticity. Weak learning leads to faster degradation of these associations, preventing spatial memory recall. The potent estrogen, 17β-estradiol (E2), increases consolidation of spatial information by increasing the strength of synaptic connections on top of learning alone, perhaps stabilizing them into a spatial engram, or ensemble of cells responsible for maintaining the memory. The specific cell types making up engrams is unknown. We hypothesize spatial learning and supplemental E2 increases pyramidal neuron activation in the DH. Our objective was to observe the effects of object training, E2 infusion into the DH, and both on hippocampal CA1 pyramidal neuron activation via the Tet-Tag viral approach. Gonadectomized male and female C57BL/6 mice were infused bilaterally with a 1:1 mixture of the activity-dependent viruses AAV9-c-fos-tTa and AAV9-TRE-EGFP and implanted with bilateral cannulae in the DH. Mice then acquired 30 s of exploration time between 2 identical objects and were bilaterally infused with vehicle or E2. Controls were handled and placed back in their cage or infused with vehicle or E2. Next, DH CA1 was sectioned and immunohistochemically labeled for overlap of DAPI, green fluorescent protein (GFP), and WFS1, to label overall cells, viral production of GFP, and pyramidal neurons, respectively. Results showed that training+E2 significantly produced more GFP tagging than other conditions in both sexes, with half of the activated cells being pyramidal neurons. These data support our hypothesis that E2 signaling and learning leads to recruitment of excitatory neurons into a hippocampal engram. Further work aims to strengthen knowledge of engram composition by determining the extent of interneuron and astrocytic activation by each condition, which will expand our understanding of memory-related neurodegenerative diseases.