Abstract：To survive in dynamic environments with uncertain resources, animals must adapt their behaviour flexibly, choosing strategies such as persevering with a current choice, exploring alternatives, or disengaging altogether. Previous studies have mainly investigated how forebrain regions represent choice costs and values as well as optimal strategies during such decisions. However, the neural mechanisms by which the brain implements alternative behavioural strategies such as persevering, exploring or disengaging, remains poorly understood. Here we identify a neural hub critical for flexible switching between behavioural strategies, the median raphe nucleus (MRN). Using cell-type specific optogenetic manipulations, fibre photometry and circuit tracing in mice performing diverse instinctive and learnt behaviours, we found that the MRN’s main cell types, GABAergic, glutamatergic (VGluT2-positive), and serotonergic neurons, have complementary functions and regulate perseverance, exploration and disengagement, respectively. Suppression of MRN GABAergic neurons, for instance through inhibitory input from lateral hypothalamus which conveys strong positive valence to the MRN, leads to perseverative behaviour. In contrast, activation of MRN VGluT2+ neurons drives exploration. Activity of serotonergic MRN neurons is necessary for general task engagement. Input from the lateral habenula conveying negative valence suppresses serotonergic MRN neurons, leading to disengagement. These findings establish the MRN as a central behavioural switchboard, uniquely positioned to flexibly control behavioural strategies. These circuits thus may also play an important role in the aetiology of major mental pathologies such as depressive or obsessive-compulsive disorders.

Biography：As a Group Leader at the University of Oxford, Dr. Ahmadlou’s research explores the neural mechanisms underlying adaptive behaviors, including how animals decide to pursue a current goal or switch to a new one. Understanding these brain mechanisms will advance the etiology of many neuropsychiatric disorders such as autism, ADHD, major depressive disorder, anxiety associated disorders, and many others, where adaptive behaviors are malfunctioned. To achieve this understanding, his lab develops novel behavior tasks and analyses, and uses cutting-edge techniques to interrogate the brain circuits in freely-moving and head-fixed mice, such as electrophysiology recording with high-density probes, miniaturized two photon and fluorescence microscopy, fiber photometry, optogenetics and pharmacological manipulations, and virus tracing, in both healthy and disordered brains. 

Before joining Oxford, he was a senior research fellow at UCL's Sainsbury Wellcome Centre, studying how the brain drives exploration. Previously, his PhD research at the Netherlands Institute for Neuroscience, which focused on visual processing and plasticity, was recognized with the 'Dutch Neuroscience Thesis Prize'.