A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory

Abstract

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received less study than NMDA receptors; thus, the reported experiments examined the role of mGluRs in familiarity discrimination in the rat PRH. Experiments 1 and 2 assessed the effects of systemic administration of MPEP, a group I mGluR (specifically mGluR5) antagonist, and/or LY341495, a group II mGluR antagonist, on a spontaneous object novelty preference task. Simultaneous antagonism of both group I and II mGluRs impaired familiarity discrimination following a 24-h but not a 15-min delay, while antagonism of either mGluR subtype alone had no effect at either delay. The impairment was in acquisition, as in Experiment 3 coadministration of MPEP and LY341495 did not affect recognition memory performance when administered either after the sample phase or prior to test. The impairment in long-term recognition memory was mediated by mGluRs in the PRH, as localized intracortical antagonism of group I and II mGluRs also produced a deficit (Experiment 4). No evidence was found for an involvement of group III mGluRs in the acquisition of long-term familiarity discrimination (Experiment 5). These findings establish that glutamatergic neurotransmission in the PRH via group I and II mGluRs is crucial for the acquisition, but not for the consolidation or retrieval of long-term object recognition memory.

Figure 1.

(A) Systemic administration of LY341495 (LY) (3 mg/kg), (B) MPEP (3 mg/kg), (C) MPEP (10 mg/kg), had no effect on familiarity discrimination. Systemic administration of LY341495 and MPEP combined (3 mg/kg each) (LY + MPEP) impaired familiarity discrimination at 24 h, but not at 15 min. (D) Drug administered before acquisition and (E) before acquisition and test. Mean discrimination ratio ±SEM (n = 12). (*) P < 0.05; (**) P < 0.01.

Figure 2.

Systemic coadministration of LY341495 (3 mg/kg) and MPEP (3 mg/kg) (LY + MPEP) had no effect on consolidation (injection post-sample) or on retrieval (injection pre-24-h test) of familiarity discrimination. Mean discrimination ratio ±SEM (n = 14).

Figure 3.

Intraperirhinal antagonism of mGluR5 and group II mGluRs impairs familiarity discrimination at 24 h. (A) Histological localization of implanted cannula. (Left) Photomicrograph; cannula tract indicated by a black line; (HPC) hippocampus. (Right) Diagram of the corresponding brain section; arrows indicate location of perirhinal cortex, and the location of each cannula tip is indicated by the dots (Swanson 1998). (B) LY (5 μM) alone (n = 7) animals tested at 24 h. (C) MPEP (100 μM) alone (n = 7) animals tested at 24 h. (D) LY (5 μM) + MPEP (100 μM) animals (n = 6) tested at 24 h, *P < 0.05. (E) EGLU (10 mM) alone (n = 9), animals tested at 24 h. (F) EGLU (10 mM) + MPEP (100 μM) animals (n < 6) tested at 20 min and 24 h, ***P < 0.001. All histograms show the mean discrimination ratio ±SEM.