Dopamine dependent setting of a circadian oscillator underlying the memory for time of day

Animals learn and remember the time of day that significant conditions occur, and anticipate recurrence at 24-h intervals, even after only one exposure to the condition. On several place-conditioning tasks, animals show context avoidance or preference only near the time of day of the experience. The memory for time of day is registered by a circadian oscillator that is set at the time of the training. We show that manipulations of dopamine (DA) neurotransmission can set a time memory in place preference and avoidance tasks, indicating that time of day is part of the context that is learned. Single injections of the DA agonist, d-amphetamine sulfate given without further exposure to the conditioning apparatus, can reset the timing of anticipatory behavior evoked by previously acquired place-event associations. The data support a model for time memory in which DA signaling sets the phase of a circadian oscillator, which returns to the same state at regular 24-h intervals. The data also raise the possibility that some apparent impairments of memory formation or retention could reflect post-experience resetting of the optimal retrieval time rather than impairment of memory or retrieval per se.