S-060
Changes in Spatial Memory and Exploration Patterns in a GluN2A Knockdown Rat Model
Fernanda Mariana Silva1, Severino Freund2, María Florencia Acutain3, María Veronica Baez4
  1. Instituto de Biología Celular y Neurociencia (IBCN)-CONICET.
  2. 1UA de HIstología, Embriología, Biología Celular y Genética. Facultad de Medicina - UBA
Presenting Author:
Fernanda Mariana Silva
fernandamariana2305@gmail.com
During embryonic stage, neurons predominantly express N-methyl-D-aspartate receptors (NMDARs) containing GluN2B regulatory subunits. After birth, and in response to neural activity, GluN2A expression is increased and GluN2A-containing NMDARs localize at synapses, supporting neuronal maturation and synaptic refinement. Our previous work showed that GluN2A knockdown (GluN2A-KD) in the hippocampus of young adult Wistar rats induced a cognitive deficit in the contextual component of an Inhibitory avoidance paradigm. Here, we evaluated the effects of GluN2A-KD on spatial memory. For this reason, three-month-old male and female rats were injected at the CA1 dorsal hippocampus with an adeno-associated viral vector carrying either a shRNA against GluN2A (2A-shRNA) or a scrambled sequence (sc-shRNA). 14 days later, animals were tested in a battery of spatial tasks (Barnes maze, reverse Barnes maze, and an object exploration task) . Male GluN2A-KD rats acquired learning criteria in the Barnes maze, whereas females did not. Both male and female GluN2A-KD rats exhibited reduced cognitive flexibility in the reverse Barnes maze. Moreover, GluN2A expression levels correlated with spatial learning indexes. In the object exploration task, GluN2A-KD rats displayed an increase in object interaction and clustering behavior compared to controls. These findings suggest that proper GluN2A expression is essential for long-term spatial memory, cognitive flexibility, and exploratory spatial patterns.