Responses of hippocampal cells can be conditioned during paradoxical sleep.

To test the hypothesis that new associations can be acquired during sleep, we developed a conditioning paradigm in which both conditioned (CS) and unconditioned (US) stimuli were non-awakening intra-cerebral stimulations. The CS was a stimulation of the Medical Geniculate body and the US a stimulation of the Central Grey. An increase in hippocampal multiunit activity to CS was taken as the conditioned response. CS-US pairings were presented across 14 sessions, with 15 trials per session and a 24-h inter-session interval. Three groups were studied: in a group the CS-US pairings were given during the awake state (group W), and in two groups pairings were presented during sleep, either slow-wave sleep (group SWS) or paradoxical sleep (group PS). In the last group, to test the possibility of transfer to the awake state of the hippocampal response acquired in PS, the CS alone were presented interspersed with periods of wakefulness. Results showed that, before pairing, CS presentation induced no change in hippocampal multiunit activity in the three groups. After pairing, no hippocampal response to CS presentation occurred in SWS. In contrast, in the W group and in the PS group, a marked increase in hippocampal activity appeared to CS. The hippocampal response in the PS group developed progressively across sessions; it occurred only two sessions later than in the W group. Moreover, when the CS-evoked response reached the asymptotic level in PS, the presentation of CS alone in awake animals elicited the hippocampal response. These results suggest that a cellular conditioning can be established during PS and that the cellular conditioned response developed in PS can be transferred to the awake state.