Waiting is one of healthcare’s core experiences. It is there in the time it takes to access services; through the days, weeks, months or years needed for diagnoses; in the time that treatment takes; and in the elongated time-frames of recovery, relapse, remission and dying.Funded by the Wellcome Trust, our project opens up what it means to wait in and for healthcare by examining lived experiences, representations and histories of delayed and impeded time.In an era in which time is lived at increasingly different and complex tempos, Waiting Times looks to understand both the difficulties and vital significance of waiting for practices of care, offering a fundamental re-conceptualisation of the relation between time and care in contemporary thinking about health, illness, and wellbeing.

Aggression is an ethologically complex behavior with equally complex underlying mechanisms. Here, I present data on one form of aggression, appetitive or rewarding aggression,  and the behavioral, cellular and system-level mechanisms guiding this behavior. First, I will present one way in which appetitive aggression is modeled in mice, and extend aggression motivation to the concept of compulsive aggression seeking and relapse.  I will then briefly highlight recent advances in computer vision and machine learning for automated scoring of aggressive behavior, the role of specific cell-types in controlling aggression reward, and close with preliminary data on the whole brain aggression reward functional connectome using light sheet fluorescent microscopy (LSFM).

Growing evidence suggests the ventral pallidum (VP) is critical for drug intake and seeking behaviors. Receiving dense projections from the nucleus accumbens as well as dopamine inputs from the midbrain, the VP plays a central role in the control of motivated behaviors. Repeated exposure to cocaine is known to alter VP neuronal firing and neurotransmission. Surprisingly, there is limited information on the molecular adaptations occurring in VP neurons following cocaine intake.To provide insights into cocaine-induced transcriptional alterations we performed RNA-sequencing on VP of mice following cocaine self-administration. Gene Ontology analysis pointed toward alterations in dendrite- and spinerelated genes. Subsequent transcriptional regulator analysis identified the transcription factor Nr4a1 as a common regulator for these sets of morphology-related genes.Consistent with the central role of the VP in reward, its neurons project to several key regions associated with cocaine-mediated behaviors. We thus assessed Nr4a1 expression levels in various projection populations.Following cocaine self-administration, VP neurons projecting to the mediodorsal thalamus (MDT) showed significantly increased Nr4a1 levels. To further investigate the role of Nr4a1 in cocaine intake and relapse, we bidirectionally manipulated its expression levels selectively in VP neurons projecting to the MDT. Increasing Nr4a1 levels resulted in enhanced relapse-like behaviors accompanied by a blockage of cocaine-induced spinogenesis.However, decreasing Nr4a1expression levels completely abolished cocaine intake and consequential relapse-like behaviors. Together, our preliminary findings suggest that drug-induced neuronal remodeling in pallido-thalamic circuits is critical for cocaine intake and relapse-like behaviors.

The anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex as in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. We investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.