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Modulation of GluN2B subunit-containing NMDA receptors expression and spatial long-term memory in medial septal immunolesioned rats

Beselia G, Dashniani M, Burjanadze M, Solomonia R, Kruashvili L, Chkhikvishvili N (2017) Modulation of GluN2B subunit-containing NMDA receptors expression and spatial long-term memory in medial septal immunolesioned rats. Neuroscience 2017 Abstracts 428.01 / UU39. Society for Neuroscience, Washington, DC.

Summary: The hippocampus is important in the formation of spatial memory in both humans and animals. The N-methyl-D-aspartate (NMDA) type of glutamate receptors in the hippocampus has been reported to be essential for spatial learning and memory as well as for the induction of synaptic plasticity. Evidence accumulated from recent studies suggest that GluN2A and GluN2B subunit-containing NMDA-Rs preferentially contribute to the induction of hippocampal LTP and LTD. Using a Morris water maze (MWM) task, the LTP- blocking GluN2A antagonist had no significant effect on any aspect of performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory consolidation.1The present study was designed to investigate the effect of selective immunolesions of cholinergic and GABA-ergic1septohippocampal projection neurons [using 192 IgG-saporin (SAP) or GAT1-1 saporin (GAT), respectively] on spatial memory assessed in MWM and NMDA receptor GluN2B subunit expression in the rat hippocampus. We used MWM training protocol with eight training trials. One day after training, probe test with the platform removed was performed to examine long-term spatial memory retrieval. We found that immunolesions of medial septal cholinergic or GABAergic neurons did not affect spatial learning as exhibited by a decreased latency to find the hidden platform across the eight training trials. Trained control and SAP treated rats spent significantly longer than chance (15 s) performances such as swimming time in test sector (where the hidden platform was1located). Moreover, they spent significantly longer in test sector than the opposite sector, confirming the establishment of long-1term memory. In contrast, the preference for test sector was abolished in medial septal GAT treated rats. Because GAT treated rats learned the location of the hidden platform during training, the result suggest that GAT level of NR2B subunit of NMDA receptor in the hippocampus was decreased significantly in the GAT treated group compared with the control and SAP treated groups.1In conclusion, our findings suggest that immunolesion of medial septal GABAergic neurons can interrupt hippocampus dependent1spatial memory, possible through modulation of NMDA receptor subunit expression in the hippocampus. Moreover, our finding that selective lesions of medial septal GABAergic neurons affect probe-test performance but not spatial learning, suggests that septohippocampal GABAergic projections are involved specifically in the consolidation or retrieval, but not in the acquisition of long- term memory.

Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)