TY - JOUR T1 - Frontostriatal circuit dynamics correlate with cocaine cue-evoked behavioral arousal during early abstinence JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0105-16.2016 SP - ENEURO.0105-16.2016 AU - Wesley C. Smith AU - Matthew H. Rosenberg AU - Leslie D. Claar AU - Victoria Chang AU - Sagar N. Shah AU - Wendy M. Walwyn AU - Christopher J. Evans AU - Sotiris C. Masmanidis Y1 - 2016/06/16 UR - http://www.eneuro.org/content/early/2016/06/16/ENEURO.0105-16.2016.abstract N2 - It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 hours of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion as measured by rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue-evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25-45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity.Significance Statement: Frontostriatal circuits are implicated in drug craving and relapse, which can be triggered during abstinence by drug-associated cues. This study used large-scale neural recordings with silicon microprobe technology to simultaneously examine prefrontal and striatal activity in cocaine-conditioned mice. We found relationships between the level of cocaine cue-evoked neural inhibition, frontostriatal network synchrony, and conditioned arousal measured via pupillometry. This work shows that pupil dilation is a highly sensitive measure of arousal to cocaine cues. Furthermore, the results demonstrate the effectiveness of using large-scale recordings spanning multiple brain areas to examine the neural correlates of interindividual variability among drug-experienced animals. ER -