| Autor: |
Frye, Hannah E., Izumi, Yukitoshi, Harris, Alexis N., Williams, Sidney B., Trousdale, Christopher R., Sun, Min-Yu, Sauerbeck, Andrew D., Kummer, Terrance T., Mennerick, Steven, Zorumski, Charles F., Nelson, Elliot C., Dougherty, Joseph D., Morón, Jose A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Biol Psychiatry |
| Popis: |
BACKGROUND: Cornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein prominently expressed in the dorsal hippocampus (dHPC), a region that plays a critical role in spatial memory and synaptic plasticity. However, effects of CNIH3 on AMPAR-dependent synaptic function and behavior have not been investigated. METHODS: We assessed a gain-of-function model of Cnih3 overexpression in the dHPC and generated and characterized a line of Cnih3(−/−) C57BL/6 mice. We assessed spatial memory through behavioral assays, protein levels of AMPAR subunits and synaptic proteins by immunoblotting, and long-term potentiation (LTP) in electrophysiological recordings. We also utilized a super-resolution imaging workflow, SEQUIN, for analysis of nanoscale synaptic connectivity in dHPC. RESULTS: Overexpression of Cnih3 in dHPC improved short-term spatial memory in female mice, but not in male mice. Cnih3(−/−) female mice exhibited weakened short-term spatial memory, reduced dHPC synapse density, enhanced expression of calcium-impermeable AMPAR (GluA2-containing) subunits in synaptosomes, and attenuated LTP maintenance compared to Cnih3(+/+) controls; Cnih3(−/−) males were unaffected. Further investigation revealed that deficiencies in spatial memory and changes in AMPAR composition and synaptic plasticity were most pronounced during the metestrus phase of the estrous cycle in female Cnih3(−/−) mice. CONCLUSION: This study identified a novel effect of sex and estrous on CNIH3’s role in spatial memory and synaptic plasticity. Manipulation of CNIH3 unmasked sexually dimorphic effects on spatial memory, synaptic function, AMPAR composition, and hippocampal plasticity. These findings reinforce the importance of considering sex as a biological variable in studies of memory and hippocampal synaptic function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
