Fig. 3: Challenged drinking strengthens seeking representation in dmPFC in compulsive and non-compulsive rats.
a Alcohol seeking was assessed by examining differences in neural population firing patterns prior to task stimuli between approach and no approach trials. Approach was determined by movement to a sipper and into a position to lick from that sipper, as assessed by animal tracking. Animals rarely stayed at one sipper between trials (see sipper occupancy in Fig. 1f prior to CS) or failed to drink if they approached the correct sipper during access (95.08% of correct approaches resulted in at least one lick). When averaged throughout the session, likelihood to approach gradually decreased (b), but when time locked to the session change point for each animal, likelihood to approach exhibited a sharp change (c clear examples, arrows mark change point trials, d mean across sessions). Pre- and post-session change point trials were identified as seeking and not-seeking trials, respectively. e Change in average firing rate between trials increased at the session change point above randomized data (firing rate change jittered by up to +/− 2 trials). (b, d, and e mean +/− sem. b and d: N = 40 Wistar sessions from 7 animals, N = 34 P rat sessions from 7 animals. e N = 6514 neurons from 14 animals over 74 sessions) f After PCA and sorting neurons by their contribution to PC 1, a large remapping in active neurons was observed across trials immediately before and after the session change point (mean over last/first three trials shown). g Trajectories for seeking and not-seeking states were shifted in population activity space. (Mean trajectory, all neurons, only the 3 PCs with large separation effect size shown for clarity. −5 (green dot) to +7 s relative to CS+ onset. Yellow sections: seeking epoch (see h).) h PC separation between seeking and not-seeking trials across all seven stable PCs for each experimental group. (Mean +/− std across PCA subsample trials, only neurons from a given experimental group.) Seeking epoch was selected to capture representations before the CS+, but avoid overlapping in time with CS+/CS−. i Representation strength increased during challenge (quinine) for both strains and was higher in compulsive rats. (Mean +/− std shown across mean PC separation values from each 0.1 s time bin (N = 20) in seeking epoch (h, yellow region). ***: p < 10−3.) Source data are provided as a Source Data file.
