Neural circuits that allow for reciprocal communication between the brain and viscera are critical for coordinating behavior with visceral activity. At the same time, these circuits are positioned to convey signals from pathologic events occurring in viscera to the brain, thereby providing a structural basis for comorbid central and peripheral symptoms. In the pons, Barrington's nucleus and the norepinephrine (NE) nucleus, locus coeruleus (LC), are integral to a circuit that links the pelvic viscera with the forebrain and coordinates pelvic visceral activity with arousal and behavior. Here, we demonstrate that a prevalent bladder dysfunction, produced by partial obstruction in rat, has an enduring disruptive impact on cortical activity through this circuit. Within 2 weeks of partial bladder obstruction, the activity of LC neurons was tonically elevated. LC hyperactivity was associated with cortical electroencephalographic activation that was characterized by decreased low-frequency (1-3 Hz) activity and prominent theta oscillations (6 -8 Hz) that persisted for 4 weeks. Selective lesion of the LC-NE system significantly attenuated the cortical effects. The findings underscore the potential for significant neurobehavioral consequences of bladder disorders, including hyperarousal, sleep disturbances, and disruption of sensorimotor integration, as a result of central noradrenergic hyperactivity. The results further imply that pharmacological manipulation of central NE function may alleviate central sequelae of these visceral disorders.Barrington's nucleus ͉ bladder obstruction ͉ electroencephalographic activity ͉ locus coeruleus O veractive bladder is a prevalent disorder, affecting 17% of the population and negatively impacting quality of life (1). Partial bladder obstruction is a common cause of overactive bladder in males and is used to model overactive bladder in laboratory animals (2). Whereas the structural and functional changes induced in bladder by partial obstruction are well studied (3, 4), the impact on brain function has been neglected. The potential for central consequences of bladder dysfunctions exists because neural circuits are present that communicate pelvic visceral status to the brain so that behavior can be coordinated with visceral functions. Barrington's nucleus (the pontine micturition center) and the locus coeruleus (LC) are integral components of a circuit that performs this task (5). Barrington's nucleus neurons project to spinal preganglionic parasympathetic neurons, where they regulate activity of the bladder and other pelvic viscera (6). These projections form the efferent limb of the micturition reflex, in which Barrington's nucleus neurons are activated by bladder distention and in response, initiate bladder contraction (7). The same Barrington's nucleus neurons project to the LC, a major norepinephrine (NE)-containing nucleus with divergent efferent projections that densely innervate the forebrain (8, 9). Among its functions, the LC regulates arousal, shifts in attention, and involv...
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