Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions

Abstract

Central noradrenergic (NA) signaling is broadly implicated in behavioral and physiological processes related to attention, arousal, motivation, learning and memory, and homeostasis. This review focuses on the A2 cell group of NA neurons, located within the hindbrain dorsal vagal complex (DVC). The intra-DVC location of A2 neurons supports their role in vagal sensory-motor reflex arcs and visceral motor outflow. A2 neurons also are reciprocally connected with multiple brain stem, hypothalamic, and limbic forebrain regions. The extra-DVC connections of A2 neurons provide a route through which emotional and cognitive events can modulate visceral motor outflow and also a route through which interoceptive feedback from the body can impact hypothalamic functions as well as emotional and cognitive processing. This review considers some of the hallmark anatomical and chemical features of A2 neurons, followed by presentation of evidence supporting a role for A2 neurons in modulating food intake, affective behavior, behavioral and physiological stress responses, emotional learning, and drug dependence. Increased knowledge about the organization and function of the A2 cell group and the neural circuits in which A2 neurons participate should contribute to a better understanding of how the brain orchestrates adaptive responses to the various threats and opportunities of life and should further reveal the central underpinnings of stress-related physiological and emotional dysregulation.

Activation of NPY receptors suppresses excitatory synaptic transmission in a taste-feeding network in the lower brain stem

“…Because A2 neurons are strongly implicated in satiety mechanisms (reviewed in Ref. 45), including those that survive decerebration (25), an alternative hypothesis to an orexigenic (excitatory) role for NPY on prehypoglossal neurons could involve the colocalization of NPY in a subset of A2 neurons (19,48). In that case, the inhibition of preoromotor neurons observed in the present study could represent a brain stem satiety pathway originating from A2 neurons in the cNST, in which the release of NPY and/or NE suppresses excitatory …”

“…Results from decerebrate preparations in which visceral signals, such as gastric load (49) and glucoprivation (15, 21), modify the amount of a palatable (sweet) stimulus that is consumed, suggest that these local pathways exert a potent influence over this consummatory circuitry (reviewed in Refs. 24,45,46). Although some amino acid-mediated excitatory and inhibitory inputs to IRt/PCRt preoromotor neurons have been identified from the rostral (gustatory) nucleus of the solitary tract (41), little is known of the neurochemical identity of other local modulatory influences on these neurons.…”

The μ-opioid receptor agonist DAMGO presynaptically suppresses solitary tract-evoked input to neurons in the rostral solitary nucleus

“…In the cNST, MOR activation suppresses ST input to A2 (Cui et al 2012) and POMC (Appleyard et al 2005) neurons, effects also compatible with an orexigenic influence since these neuronal populations have been implicated in satiety (Rinaman 2011). Although early reports suggested that rNST DAMGO infusions also increased food intake (Kotz et al 1997), these studies used rather large infusions and the feeding effect was delayed, suggesting that the orexigenic effect may have arisen from ligand spread that suppressed satiety signals in cNST (Kinzeler and Travers 2011).…”

Nicotinic Regulation of Energy Homeostasis

“…Noradrenaline transmission has different effects. Noradrenaline increases in PVH at the onset of the periods of food intake and stimulates carbohydrate intake through binding to α2 receptors (Alexander, Cheung, Dietz, & Leibowitz, 1993); however, noradrenaline in the NTS-PVH pathway is also a principal mediator of several satiation stimuli (Rinaman, 2011).…”