Neuronal and behavioral correlations in the medial prefrontal cortex and nucleus accumbens during cocaine self-administration by rats

Up to 31 neurons per animal were simultaneously recorded from the medial pr efrontal cortex and nucleus accumbens in 15 rats during i.v. cocaine self-a dministration sessions, using a multi-channel, single-unit recording techni que. Alterations of neuronal activity (both excitatory and inhibitory) were found a few seconds before each lever press for cocaine infusion; we have called these pre-lever press neuronal activations "anticipatory responses". A derailed video analysis revealed that these neuronal firing alterations were associated with specific portions of the behavioral sequence performed before each lever press in both recording areas. Some of the simultaneousl y recorded neurons displayed similar firing patterns in relation to a given behavioral episode within the behavioral sequence (turning, raising head, etc.), while others fired at different times relative to each behavioral ev ent, Cross-correlational analyses revealed inter-regional and intra-regiona l correlated firing patterns between pairs of simultaneously recorded media l prefrontal cortex and nucleus accumbens neurons. This correlated firing o ccurred in the neurons with and without anticipatory responses, although th e incidence of correlations between anticipatory neuron pairs was much high er than that between non-anticipatory neuron pairs (18.4% vs 3.6%), Many co rrelated neuron pairs displayed a time lag in the peak of correlational act ivity that indicated a temporal sequence in correlated activity. In contrad iction to our hypothesis, the temporal pattern of correlation reveals that there are more cases in which nucleus accumbens neurons fired ahead of medi al prefrontal cortex neurons. The results suggest that multiple mesocorticolimbic neuronal circuits may c ode sequential steps during the behavioral sequence performed to obtain an infusion of cocaine. The observed correlated firing between the medial pref rontal cortex and the nucleus accumbens indicates that dynamic, coherent ac tivity occurs within the mesocorticolimbic circuit. Because this circuit is hypothesized to drive drug-seeking behavior, we suggest that this correlat ed firing between the nucleus accumbens and the medial prefrontal cortex ma y participate in the control of cocaine self-administration. In addition, t he finding that correlated activity within the nucleus accumbens more often precedes that of the medial prefrontal cortex suggests that the nucleus ac cumbens may play a prime role in the initiation of cocaine self-administrat ion. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.