Recruitment of hippocampal neurons to encode behavioral events in the rat: Alterations in cognitive demand and cannabinoid exposure

Successful performance by rats of a delayed-nonmatch-to-sample (DNMS) task is hippocampal dependent. We have shown that neurons in hippocampus differentially encode task-relevant events. These responses are critical for correct DNMS performance and are diminished by exogenous cannabinoids. We therefore reasoned that hippocampal neural correlates of behavior are likely shaped during learning; however, to date, no work has examined these correlates during DNMS acquisition training. Consequently, the present study assessed the emergence of hippocampal neural encoding when (i) cognitive task demands were increased through prolongation of delay intervals between sample and nonmatch phase and (ii) when animals are under cannabinoid treatment and performance is compromised. Adult, male Long-Evans rats were trained to perform the DNMS task without delay and then implanted with multielectrode recording arrays directed to CA3 and CA1 subfields of the hippocampus. Following recovery, single units were isolated and animals divided into two treatment groups: vehicle or WIN 55,212-2 (WIN-2, 0.35 mg/kg). Ensemble firing was monitored during retraining in DNMS task at 0 s, and subsequently delay intervals were progressively increased to 1-10 s, 11-20 s, and 21-30 s when animals met criterion (80% correct) at each respective interval. Hippocampal CA3 and CA1 principal cells were isolated and recorded throughout treatment. Extension of the delay led to an increase in the number of task-correlated neurons in controls. This recruitment of novel cells was reduced/prevented in the presence of WIN-2 and was paralleled by impairment in acquisition learning at longer delay intervals. Moreover, WIN-2 suppressed hippocampal ensemble firing during the sample (encoding) but not nonmatch phase of the DNMS task across all delays. These cannabinoid-induced alterations in hippocampal neuronal activity may explain the observed deficits in DNMS performance.