Evaluating the neural basis of temporal order memory for visual stimuli in the rat.

Temporal order memory (memory for stimulus order) is crucial for discrimination between familiar objects and depends upon a neural circuit involving the perirhinal cortex (PRH) and medial pre-frontal cortex. This study examined the role of glutamatergic and cholinergic neurotransmission in the encoding or retrieval of temporal order memory, using a task requiring the animals to discriminate between two familiar objects presented at different intervals. 6-Cyano-7-nitroquinoxaline (CNQX) (AMPA/kainate receptor antagonist), scopolamine (muscarinic receptor antagonist) or 2-amino-5-phosphonopentanoic acid (AP5) (N-methyl-D-aspartate receptor antagonist) was administered before sample phase 2 (to be active during encoding) or before test (to be active during retrieval). Unilateral CNQX administration into the PRH and pre-limbic/infra-limbic cortices (PL/IL) in opposite hemispheres, i.e. to disrupt neurotransmission within the circuit, impaired encoding and retrieval. Administration of scopolamine or AP5 in the PRH-PL/IL circuit impaired encoding. Drug effects in each brain region were then investigated separately. Intra-PRH CNQX, scopolamine or AP5 disrupted encoding, such that the animals explored the recent object significantly more than the old object. In contrast, intra-PL/IL CNQX, scopolamine or AP5 impaired memory performance such that the animals spent an equal amount of time exploring the objects. CNQX but not AP5 or scopolamine impaired retrieval. Furthermore, CNQX impaired novel object preference when infused into the PRH but not PL/IL following a 3 h delay. Thus, encoding of temporal order memory is mediated by plastic processes involving N-methyl-D-aspartate and muscarinic receptors within the PRH-PL/IL circuit, but these two regions make qualitatively different cognitive contributions to the formation of this memory process.