Datensatz

Zusammenfassung

The brainstem noradrenergic nucleus, locus coeruleus (LC), is a component of disparate theories of brain function, including those concerning decision making, control of sleep and wakefulness, computational models of learning, sensory salience, and the physiology of correlated brain activity (ensembles/networks) and of hemodynamic responses (fMRI). Moreover, the LC has long been a clinical treatment target for a range of neuropsychiatric and neurological disorders (mood disorders, PTSD, ADHD, chronic pain) and its degeneration is implicated in Alzheimer’s. The role of the LC in such diverse brain functions and diseases may be due to its global projections throughout the central nervous system transmitting a homogenous noradrenergic signal. We present the emerging perspective of a modular and heterogeneous LC that provides targeted neuromodulation. This new perspective requires updating theories relevant to systems and computational neuroscientists, pharmacologists, and psychologists. Speakers will provide a primer on state-of-the-art methods and review their findings on LC development, genetics, and physiology in animal models of anxiety and cognition. N. Totah will present large-scale recordings of LC single units and evidence that LC neuronal ensembles consisting of different cell types provide targeted neuromodulation. L. Schwarz will present anatomical and in vivo imaging studies that demonstrate how a specific subset of LC neurons projecting to the forebrain facilitate behavioral flexibility in mice. D. Chandler will present the results of studies investigating how specific LC efferent pathways adapt in response to acute stressor exposure and how they contribute to the generation of anxiety-like behavior. T. Pickering will describe how the organizational specialization of the LC can both act to suppress painful sensitization while also signaling its salience and he will consider how this discrete modularity is defined and its consequences for sensory inference and action planning. J. McCall will present anatomical and electrophysiological evidence for segregated contributions of afferent and efferent LC circuits in negative affective behaviors. P. Jensen will describe how viral and intersectional genetic strategies are uncovering the developmental and molecular basis of LC heterogeneity, including its complex pattern of axonal projections and their behavioral correlates. Collectively, the speakers will advance the view that progress in understanding the role of the LC in behavior, brain function, and neuropsychiatric and neurological disorders will require attention to the modular nature of the LC.