Distinct Contributions of Hippocampal NMDA and AMPA Receptors to Encoding and Retrieval of One-Trial Place Memory

Abstract

Allocentric place memory may serve to specify the context of events stored in human episodic memory. Recently, our laboratory demonstrated that, analogous to event-place associations in episodic memory, rats could associate, within one trial, a specific food flavor with an allocentrically defined place in an open arena. Encoding, but not retrieval, of such flavor-place associations required hippocampal NMDA receptors; retrieval depended on hippocampal AMPA receptors. This might have partly reflected the contributions of these receptors to encoding and retrieval of one-trial place, rather than flavor-place, memory. Therefore, the present study developed a food-reinforced arena paradigm to study encoding and retrieval of one-trial allocentric place memory in rats; memory relied on visuospatial information and declined with increasing retention delay, still being significant after 6 h, the longest delay tested (experiments 1 and 2). Hippocampal infusion of the NMDA receptor antagonist D-AP-5 blocked encoding without affecting retrieval; hippocampal infusion of the AMPA receptor antagonist CNQX impaired retrieval (experiment 3). Finally, we confirmed that the D-AP-5 infusions selectively blocked induction of long-term potentiation, a form of synaptic plasticity, whereas CNQX impaired fast excitatory transmission, at perforant-path dentate gyrus synapses in the dorsal hippocampus in vivo (experiment 4). Our results support that encoding, but not retrieval, of one-trial allocentric place memory requires the NMDA receptor-dependent induction of hippocampal synaptic plasticity, whereas retrieval depends on AMPA receptor-mediated fast excitatory hippocampal transmission. The contributions of hippocampal NMDA and AMPA receptors to one-trial allocentric place memory may be central to episodic memory and related episodic-like forms of memory in rats.

Improved Long-Term Potentiation and Memory in Young Tau-P301L Transgenic Mice before Onset of Hyperphosphorylation and Tauopathy

“…One possibility is a differential stabilization of MTs by tau that could contribute importantly to vesicular transport (Zhang et al, 2005) and in turn to synaptic plasticity and memory. The trafficking of NMDA and AMPA receptors, critically implicated in LTP and memory formation (Davis et al, 1992;Malinow and Malenka, 2002;Bast et al, 2005), depends heavily on stable MT-mediated transport (Setou et al, 2000(Setou et al, , 2002Yuen et al, 2005). Possibly, MT stability is improved in the tau-P301L mice, despite a possible reduced binding of mutant tau (Hong et al, 1998;Perez et al, 2000;Zhang et al, 2004), which could, however, be balanced by the higher concentration of tau.…”

Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

“…Thus, one should consider the possibility that the lentivirus-based expression of a dnWNT interfered with synaptic plasticity in post-mitotic granule cells. However, previous work has indicated that blocking hippocampal synaptic plasticity (by blocking NMDA receptors and LTP) does not impair spatial memory retention in the water maze but does impair acquisition (Steele and Morris 1999;Day and Morris 2001;Bast et al 2005). Because our findings are the reverse (intact acquisition, impaired retention) of this pattern of impairment, it is unlikely that impaired synaptic plasticity of post-mitotic granule cells was a contributing factor.…”

NMDA Receptor Subunit NR2A Is Required for Rapidly Acquired Spatial Working Memory But Not Incremental Spatial Reference Memory

“…The SWM deficit in NR2A Ϫ/Ϫ mice is consistent with previous pharmacological studies. AP5 produces SWM impairments in a number of experimental paradigms, suggesting a crucial and obligatory role for NMDARs in a rapid, flexible hippocampal memory system (Tonkiss and Rawlins, 1991;Steele and Morris, 1999;Lee and Kesner, 2002;Day et al, 2003;Bast et al, 2005). More recently, we have shown that acute infusion of D-AP5 directly into dorsal hippocampus impairs SWM performance on the T-maze rewarded alternation task (McHugh et al, 2008).…”