The Different Effects on Recognition Memory of Perirhinal Kainate and NMDA Glutamate Receptor Antagonism: Implications for Underlying Plasticity Mechanisms

Abstract

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay. For both drugs, impairment was found when the drug was present during acquisition but not when it was present during retrieval. Experiments in vitro indicate that selective antagonism of NMDA receptors containing NR2A subunits blocks perirhinal long-term potentiation (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long-term depression (LTD). However, recognition memory after a 24 h delay was impaired only when both an NR2A and an NR2B antagonist were infused together, not when either was infused separately. These results establish that kainate receptors have a role in recognition memory that is distinct from that of NMDA receptors, that there must be at least two independent underlying memory mechanisms in the infused region, that this region and no other is necessary for both short-term and long-term familiarity discrimination, and that perirhinal-dependent long-term recognition memory does not rely solely on processes used in NMDA-dependent LTP or LTD (although it might be independently supported by components of each type of process with one substituting for the other).

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

“…The bulk of research on synaptic plasticity within the perirhinal cortex has focussed on long-term depression (LTD) due to its possible role in recognition memory (see below and Jerusalinsky et al, 1997;Warburton et al, 2003;Wan et al, 2004;Barker et al, 2006a;Griffiths et al, 2008;Seoane et al, 2009). Ziakopoulos et al (1999) demonstrated that the perirhinal cortex could also undergo depressive synaptic plasticity; short-term depression in the form of paired-pulse depression (PPD) could be induced with a 200 ms IPI and this PPD was GABA B -dependent (Ziakopoulos et al, 2000).…”

“…There is much evidence to support this claim as glutamatergic signalling, crucial for synaptic plasticity, is also required for object recognition memory (de Lima et al, 2005;Winters and Bussey, 2005b;Barker et al, 2006a;Nilsson et al, 2007;Barker and Warburton, 2008). In rats, the perirhinal administration of AP-5 (Winters and Bussey, 2005b;Barker et al, 2006a) or systemic administration of MK-801 (de Lima et al, 2005;Nilsson et al, 2007) impairs object recognition tasks performance by disrupting glutamatergic signalling via the NMDA receptor.…”

“…In rats, the perirhinal administration of AP-5 (Winters and Bussey, 2005b;Barker et al, 2006a) or systemic administration of MK-801 (de Lima et al, 2005;Nilsson et al, 2007) impairs object recognition tasks performance by disrupting glutamatergic signalling via the NMDA receptor. Similar pharmacological challenges of the NMDA receptor also disrupt perirhinal LTP and LTD (Ziakopoulos et al, 1999;Cho et al, 2000;Karasawa et al, 2008).…”

“…The AMPA receptor has also been implicated in both object recognition memory (Winters and Bussey, 2005b) as well as baseline neuronal transmission (Park et al, 2006) and synaptic plasticity (Griffiths et al, 2008) in the perirhinal cortex. Additionally, a role for the kainate receptor in object recognition memory (Barker et al, 2006a) and perirhinal synaptic plasticity (Park et al, 2006) has been proposed. Functional dissociations have already been shown between NMDA and kainate receptors; kainate receptors mediate recognition memory at short but not long delays whereas NMDA receptors mediate recognition memory at long but not short delays (Barker et al, 2006a).…”

“…Additionally, a role for the kainate receptor in object recognition memory (Barker et al, 2006a) and perirhinal synaptic plasticity (Park et al, 2006) has been proposed. Functional dissociations have already been shown between NMDA and kainate receptors; kainate receptors mediate recognition memory at short but not long delays whereas NMDA receptors mediate recognition memory at long but not short delays (Barker et al, 2006a). In another study, Barker et al (2006b) demonstrate that perirhinal mGlu receptors are also involved in recognition memory.…”