title: Frontostriatal Circuit Dynamics Correlate with Cocaine Cue-Evoked Behavioral Arousal during Early Abstinence.
abstract: 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 h 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 the 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.
authors.affiliation: Interdepartmental PhD Program in Neuroscience, University of California, Los Angeles , Los Angeles, California 90095.
authors.forename: Wesley C
authors.identifier: 0000-0002-7361-7760
authors.initials: WC
authors.lastname: Smith
authors.affiliation: Department of Neurobiology, University of California, Los Angeles , Los Angeles, California 90095.
authors.forename: Matthew H
authors.identifier: 0000-0002-8055-9343
authors.initials: MH
authors.lastname: Rosenberg
authors.affiliation: Department of Bioengineering, University of California, Los Angeles , Los Angeles, California 90095.
authors.forename: Leslie D
authors.identifier: 0000-0002-4030-9171
authors.initials: LD
authors.lastname: Claar
authors.affiliation: Undergraduate Interdepartmental Program for Neuroscience, University of California, Los Angeles , Los Angeles, California 90095.
authors.forename: Victoria
authors.identifier: 0000-0003-4202-8311
authors.initials: V
authors.lastname: Chang
authors.affiliation: Undergraduate Interdepartmental Program for Neuroscience, University of California, Los Angeles , Los Angeles, California 90095.
authors.forename: Sagar N
authors.initials: SN
authors.lastname: Shah
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095; Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095; Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Wendy M
authors.identifier: 0000-0003-1192-3065
authors.initials: WM
authors.lastname: Walwyn
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095; Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095; Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Evans
authors.affiliation: Interdepartmental PhD Program in Neuroscience, University of California, Los Angeles, Los Angeles, California 90095; Department of Neurobiology, University of California, Los Angeles, Los Angeles, California 90095; Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095; Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Sotiris C
authors.initials: SC
authors.lastname: Masmanidis
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003344:Cortical Synchronization / Q000187:drug effects / Q000502:physiology; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011680:Pupil / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D066328:Ventral Striatum / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
keywords: cocaine; conditioned arousal; large-scale recordings; prefrontal cortex; pupillometry; striatum