Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance

Abstract

This Review highlights the processing and integration performed by hindbrain nuclei, focusing on the inputs received by nucleus tractus solitarius (NTS) neurons. These inputs include vagally mediated gastrointestinal satiation signals, blood-borne energy-related hormonal and nutrient signals, and descending neural signals from the forebrain. We propose that NTS (and hindbrain neurons, more broadly) integrate these multiple energy status signals and issue-output commands controlling the behavioral, autonomic, and endocrine responses that collectively govern energy balance. These hindbrain-mediated controls are neuroanatomically distributed; they involve endemic hindbrain neurons and circuits, hindbrain projections to peripheral circuits, and projections to and from midbrain and forebrain nuclei.

Figure 1

a: Afferent input to NTS neurons. The figure highlights input to medial NTS neurons from blood borne energy status signals such as leptin, ghrelin, and glucose, from the gastrointestinal tract (via the vagus nerve) that processing of sensory signals of gastrointestinal origin as well as responding to leptin and other energy status signals, and from hypothalamic neurons (PVH, LH and ARH) that themselves are responsive to energy status signals. For clarity inputs to medial NTS neurons from other parts of the brain and inputs to neurons in other regions of the NTS that receive cranial nerve input of oral (gustatory) and thoracic origin are not included. Figure 1b: Output from NTS neurons. NTS neurons from caudal regions (cNTS) project: to vagal efferent neurons in DMV to control parasympathetic gastrointestinal responses including insulin secretion and gastric emptying; to the intermediolateral cell column of the spinal cord along with projections from neurons in other regions of the hindbrain (RPa, VLM, PBN) and hypothalamus (POA, DMH, ARH) to control sympathetic efferent responses of relevance to energy expenditure and gastrointestinal responses; and to PVH neurons to influence neuroendocrine responses. Neurons from rostral regions of NTS (rNTS) and PBN neurons project to the parvocellular reticular formation (PCRt) to control ingestive consummatory (licking, chewing, swallowing, rejection) response. For clarity input to these response pathways from other brain regions, not highlighted in text, are not included Figure 1c: Rostral projections of NTS neurons. The labeled structures receive monosynaptic projections from neurons located in different regions of the NTS. For clarity other projections of NTS neurons to sites within the hindbrain and to the periphery are not shown.