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Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis.

ABSTRACT: Central norepinephrine signaling influences a wide range of behavioral and physiological processes, and the ventral bed nucleus of the stria terminalis (vBNST) receives some of the densest norepinephrine innervation in the brain. Previous work describes norepinephrine neurons as projecting primarily unilaterally; however, recent evidence for cross-hemispheric catecholamine signaling challenges this idea. Here, we use fast-scan cyclic voltammetry and retrograde tracing to characterize cross-hemispheric norepinephrine signaling in the vBNST. We delivered stimulations to noradrenergic pathways originating in the A1/A2 and locus coeruleus and found hemispherically equivalent norepinephrine release in the vBNST regardless of stimulated hemisphere. Unilateral retrograde tracing revealed that medullary, but not locus coeruleus norepinephrine neurons send cross-hemispheric projections to the vBNST. Further characterization with pharmacological lesions revealed that stimulations of the locus coeruleus and its axon bundles likely elicit vBNST norepinephrine release through indirect activation. These experiments are the first to demonstrate contralateral norepinephrine release and establish that medullary, but not coerulean neurons are responsible for norepinephrine release in the vBNST.

SUBMITTER: Fox ME

PROVIDER: S-EPMC5177450 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims: Thermoregulatory responses in homeothermic animals, including humans, are classified into involuntary autonomous and voluntary behavioral thermoregulatory responses. Although behavioral thermoregulatory responses are probably driven by positive (pleasant) and/or negative (unpleasant) emotions, the neuronal mechanisms underlying the induction of negative emotions by hot and cold environments remain poorly understood. The bed nucleus of the stria terminalis is a brain region implicated in stress responses and negative emotions, such as fear, anxiety, and aversion. Various stimuli that cause negative emotions, such as immobilization stress, fox odor, gastric distension, and inflammatory pain, increase noradrenaline release in the rat bed nucleus of the stria terminalis, especially in the ventral bed nucleus of the stria terminalis. It has been reported that the negative emotional component of pain is mediated by noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis. However, the role of intra-ventral bed nucleus of the stria terminalis noradrenergic neurotransmission in the induction of negative emotion by exposure to hot and cold environments remains to be elucidated. For the first step to address this issue, the effects of hot and cold environments on noradrenaline release in the ventral bed nucleus of the stria terminalis were examined.Methods: In vivo microdialysis analyses in unanesthetized, freely moving male Sprague-Dawley rats were performed to examine hot and cold environments-induced noradrenaline release in the ventral bed nucleus of the stria terminalis.Results: Exposure to hot (38°C) and cold (8°C) environments significantly increased noradrenaline release in the ventral bed nucleus of the stria terminalis.Conclusions: The results suggest that exposure to hot and cold environments enhances noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis, which may induce negative emotion, and thereby drive avoidance behaviors, that is, escape from hot and cold environments.

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Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis.

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