Cornichon Homolog-3 (CNIH3) Modulates Spatial Memory in Female Mice
| Autor: | Sidney B. Williams, Hannah E. Frye, Christopher R. Trousdale, Jose A. Morón, Elliot C. Nelson, Joseph D. Dougherty |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Hippocampal synaptic plasticity
0303 health sciences AMPA receptor Biology Barnes maze Postsynaptic membrane 03 medical and health sciences 0302 clinical medicine nervous system Knockout mouse Spatial learning Excitatory postsynaptic potential Latency (engineering) Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/724104 |
| Popis: | Cornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein that traffics AMPARs to the postsynaptic membrane and potentiates AMPAR signaling. AMPARs are key components of hippocampal synaptic plasticity and memory formation, however the role of CNIH3 in memory has yet to be elucidated. To study the role of CNIH3 on mouse behavior, we bred and characterized a line of Cnih3-/- mice from C57BL/6 Cnih3tm1a(KOMP)Wtsi mice obtained from the Knockout Mouse Project (KOMP). In agreement with previous studies of CNIH3 in the brain, we observed concentrated expression of Cnih3 in the dorsal hippocampus, a region associated with spatial learning and memory. Therefore, we tested Cnih3+/+, Cnih3+/-, and Cnih3-/- mice in the Barnes maze paradigm to measure spatial memory. We observed no change in spatial memory in male Cnih3+/- and Cnih3-/- mice compared to male Cnih3+/+ controls, however, Cnih3-/- female mice made significantly more primary errors, had a higher primary latency, and took less efficient routes to the target in the maze compared to Cnih3+/+ female mice. Next, to investigate an enhancement of spatial memory by Cnih3 overexpression, specifically in the dorsal hippocampus, we developed an AAV5 viral construct to express wild-type Cnih3 in excitatory neurons. Female mice overexpressing Cnih3 made significantly fewer errors, had a lower primary latency to the target, and took more efficient routes to the maze target compared to YFP expressing control females. No change in spatial memory was observed in male Cnih3 overexpression mice. This study, the first to identify sex-specific effects of the AMPAR auxiliary protein CNIH3 on spatial memory, provides the groundwork for future studies investigating the role of CNIH3 on sexually dimorphic AMPAR-dependent behavior and hippocampal synaptic plasticity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|