Presynaptic NR2A-containing NMDARs are required for LTD between the amygdala and the perirhinal cortex: a potential mechanism for the emotional modulation of memory?

Abstract

Visual recognition memory relies on long-term depression like mechanisms within the perirhinal cortex and the activation of the lateral amygdala can enhance visual recognition memory. How the lateral amygdala regulates recognition memory is not known but synaptic plasticity at amygdala-perirhinal synapses may provide a mechanism for the emotional enhancement of recognition memory. In this study we investigate the mechanisms of long-term depression (LTD) at the amygdala-perirhinal synapse in male Lister Hooded rats. We demonstrate that LTD at this input relies on NR2A-containing NMDARs, located presynaptically. Therefore, the underlying mechanisms of LTD, at the amygdala-perirhinal input, which may regulate the emotional context for recognition memory, are different to previously described postsynaptic NR2B-NMDAR mechanisms of intraperirhinal LTD that subserve recognition memory.

Significance Statement: Emotional events are better remembered than emotionally neutral events. The ability of memory enhancement by emotion is dependent on amygdala-mediated alterations of synaptic activity. The amygdala has robust connections with perirhinal cortex, modulating synaptic transmission and plasticity within this region. The perirhinal cortex is necessary for visual-objection recognition, relying on long-term-depression for memory. Despite the importance of emotion to modulate memory in perirhinal cortex the mechanisms are unknown. We provide the first demonstration of the mechanisms underlying LTD at this synapse, dependent on presynaptically-located NR2A-containing NMDARs. We show a role for NMDARs in amygdala-perirhinal plasticity, and that the mechanisms described here are different to those of amygdala-perirhinal LTP (NMDAR-independent) and intraperirhinal plasticity (NMDAR-dependent), both of which are induced postsynaptically.