Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

Abstract

A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt) neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP) can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT) can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools has greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

Keywords: AgRP; Hcrt; OVLT; hypocretin; hypothalamus; optogenetics; orexin; pharmacogenetics.

Figure 1

(A) Downstream projections from hypocretin (Hcrt) neurons and their (B) potential functional roles in wakefulness and arousal. Arc, arcuate nucleus; BF, basal forebrain; BNST; bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; DRN, dorsal raphe nuclei; IML, intermediolateral cell column of the spinal cord; LC, locus coeruleus; LH, lateral hypothalamus; MPOA, median preoptic area; NAc, nucleus accumbens; NTS, nucleus of the solitary tract; PreBötz, preBötzinger complex; PVH, paraventricular hypothalamus; RVLM, rostroventral lateral medulla; TMN, tuberomammilary nucleus; vlPAG, ventrolateral periaqueductal gray; VMH, ventromedial hypothalamic nucleus; VTA, ventral tegmental area.

Figure 2

(A) Downstream projections from AgRP neurons and (B) their potential functional roles in food-seeking behavior. BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; LH, lateral hypothalamus; PAG, periaqueductal gray; PBN, parabrachial nucleus; PVH, paraventricular hypothalamus; PVT, paraventricular thalamic nucleus.

Figure 3

(A) Downstream projections from OVLT neurons and (B) their potential functional roles in water-seeking behavior. ACC, anterior cingulate cortex; PBN, parabrachial nucleus; PVH, paraventricular hypothalamus; SON, supraoptic nucleus; vlPAG, ventrolateral periaqueductal gray.