Central Neurocircuits Regulating Food Intake in Response to Gut Inputs-Preclinical Evidence

Kirsteen N Browning, Kaitlin E Carson, Kirsteen N Browning, Kaitlin E Carson

Abstract

The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.

Keywords: brainstem; feeding; gastrointestinal; vagus.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the neuroanatomical connections between the gastrointestinal (GI) tract and brainstem vagal nuclei involved in the regulation of food intake. Sensory information from the GI tract is relayed centrally via the afferent vagus which responds both directly (via neuropods) and indirectly (via paracrine signaling) to gastrointestinal stimulation. At the level of the dorsal hindbrain, afferent vagal inputs enter the brainstem via the tractus solitarius (TS) and terminate on neurons of the nucleus of the tractus solitarius (NTS). The integrated signal is relayed from the NTS to the adjacent dorsal motor nucleus of the vagus (DMV) via catecholaminergic, glutamatergic, and predominantly gamma aminobutyric acid (GABA)-ergic, synapses. The DMV contains preganglionic parasympathetic motoneurons that relayed the resulting output signal to the GI tract via the efferent motor vagus. EEC—enteroendocrine cells; CC—central canal.
Figure 2
Figure 2
Schematic representation of the neuroanatomical connections between the gastrointestinal (GI) tract and central nervous system nuclei involved in regulation of GI functions and feeding. Note the location of the nuclei are not intended to be anatomically accurate. AP—area postrema; NTS—nucleus of the tractus solitarius, DMV—dorsal motor nucleus of the vagus; DVC—dorsal vagal complex; PBN—parabrachial nucleus; VTA/SN—ventral tegmental area/Substantia Nigra; PVN—paraventricular nucleus of the hypothalamus; VMH—ventromedial hypothalamus; LH—lateral hypothalamus; ARC—arcuate nucleus; CeA—central nucleus of the amygdala; BNST—bed nucleus of the stria terminalis.

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