Noradrenergic and Cholinergic Mechanisms Underlying Pupil-Linked Arousal Modulation of Thalamic Sensory Processing

Columbia Univ New York Morningside, New York NY

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Abstract

Project Summary Neuromodulatory systems, including the locus coeruleus – norepinephrine (LC-NE) system (i.e. noradrenergic system), exert heavy influences on sensory perception and perceptual behavior. In sensory pathways, the thalamus is strategically positioned to dynamically gate information flow to the cortex. Previous work has demonstrated that the timing across population thalamic neurons switched the nature of information flow to the cortex and the switch was manifested in perceptual behavior. More recent work showed that LC activation increased the feature selectivity of individual thalamic relay neurons, and this improvement was due to LC regulation of the interplay between the thalamic relay nucleus and thalamic reticular nucleus. However, how the population coding of sensory information by thalamic neurons is modulated by the LC-NE system remains mostly unknown. The LC is the primary source of norepinephrine to the forebrain, and the malfunction of the LC-NE system has been implicated in major clinical disorders, including schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease, attention deficit hyper-activity disorder (ADHD), and depression. Moreover, abnormal activity in the thalamus has been implicated in brain disorders, including PD, central pain syndrome, and depression. The diversity supplement project will examine the influence of the LC – NE system on thalamic population coding of tactile signals. More specifically, using neuropixels recording in awake thalamus in concert with chemogenetic stimulation of the LC, we will 1) characterize the population coding of a variety of properties of tactile signals, including amplitude, velocity, and direction etc., for neurons in the thalamic relay nucleus and thalamic reticular nucleus with and without LC stimulation, and 2) examine the contribution of thalamic population response to tactile detection performance with and without LC stimulation. This project will provide much-needed insight about how the LC-NE systems modulates thalamic sensory processing. Such information is essential to better understand neurological disorders in which abnormal thalamic activity and noradrenergic activity have been reported.