ReviewVisceral sensory inputs to the endocrine hypothalamus
Introduction
Interoceptive feedback signals from the body are conveyed to widely distributed regions of the central nervous system (CNS),1 including regions of the hypothalamus and limbic forebrain that initiate and modulate autonomic and endocrine homeostatic processes. This review article describes the organization of central neural pathways that transmit sensory signals from thoracic and abdominal viscera to endocrine neurons in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. A special emphasis is placed on viscerosensory inputs to parvocellular corticotropin releasing factor (CRF)-containing PVN neurons that control anterior pituitary release of adrenocorticotropic hormone (ACTH), and on inputs to magnocellular PVN and SON neurons that release vasopressin (AVP) or oxytocin (OT) from their axon terminals in the posterior pituitary. The postnatal development of these ascending pathways also is considered. In laboratory rats, central visceral sensory pathways undergo a significant amount of synaptic assembly and refinement during the first two weeks of postnatal life. The anatomical and functional maturation of interoceptive inputs to the endocrine hypothalamus appears to parallel the organism’s newly emerging ability to respond physiologically to certain environmental challenges.
Section snippets
Visceral sensory inputs to spinal cord and caudal brainstem
Sensory signals from the viscera are carried to the CNS by spinal and cranial afferents. In rats, spinal viscerosensory afferents terminate in laminae I–VII of the dorsal horn and intermediate zone, and in lamina X around the central canal [36]. Inputs from visceral and somatic sensory afferents converge onto common second order neurons within the spinal dorsal horn. A subset of these neurons convey the convergent somato- and viscerosensory signals to the diencephalon via the anterolateral
Central visceral sensory pathways to the endocrine hypothalamus
As summarized in Fig. 1, visceral sensory signals are relayed from the NST to the endocrine hypothalamus via direct and indirect ascending pathways [8], [43], [46], [112]. The indirect pathways include relays from the area postrema (AP) and NST to the VLM [8], [15], [53], [117] and PBN [24], [52], [80], [128]. The AP is a circumventricular organ with a reduced or absent blood–brain barrier. Projections from AP neurons to the subjacent NST and also directly to the VLM and PBN [24], [64], [128]
Viscerosensory recruitment of neural inputs to the endocrine hypothalamus
The ability of visceral sensory stimuli to affect pituitary hormone release has been appreciated for many years. Early studies demonstrated posterior pituitary release of antidiuretic and milk-ejection factors (i.e., AVP and OT, respectively) in rats after electrical stimulation of the central end of the cut vagus nerve [16], [31], [78], [79], [131]. A series of studies by Ueta and colleagues subsequently demonstrated that gastrointestinal and vagal stimulation promotes significant activation
Viscerosensory inputs to the endocrine hypothalamus are primarily noradrenergic
Viscerosensory projections from the NST and VLM to the PBN, hypothalamus, CeA, and BNST are primarily (although not exclusively) catecholaminergic, arising from nor/adrenergic A2/C2 neurons within the NST and A1/C1 neurons within the VLM [116], [117], [119]. For convenience, in this article catecholaminergic NST and VLM projection neurons are referred to collectively as noradrenergic (NA) neurons, because they all are immunoreactive for the NA synthetic enzyme dopamine beta hydroxylase (DbH).
Non-catecholaminergic viscerosensory inputs to the hypothalamus
Ascending NA projections to the hypothalamus and limbic forebrain are paralleled by projections arising from a separate and smaller population of non-NA neurons with widely arborizing axon terminals, whose cell bodies are located in the caudal NST and adjacent reticular formation. These neurons appear to co-express immunoreactivity for multiple peptides, including glucagon-like peptide 1 (GLP-1) [48], [65], [74], [119], [120], [121]. The synaptic targets of GLP-1 neurons include CRF neurons in
Postnatal development of viscerosensory inputs to the endocrine hypothalamus
The natural process of neural circuit development offers special opportunities to probe the functional organization of ascending viscerosensory pathways. Developmental research in this area has been fairly limited, but the results are intriguing. The first few postnatal weeks in rats correspond to a so-called “stress hyporesponsive period” (SHRP) characterized by reduced or absent HPA axis responsiveness to certain types of stressors [92], [114], [143], including interoceptive stressors [99],
Conclusion
Visceral sensory information reaches the endocrine hypothalamus via central neural pathways that are primarily, but not exclusively, noradrenergic. NA and complementary peptidergic (e.g., GLP-1) inputs to magnocellular and parvocellular endocrine neurons within the SON and PVN arise directly from medullary NST and VLM neurons, with additional viscerosensory inputs relayed through the pontine PBN and other central sites. The functional importance of these pathways for modulating and driving HPA
References (151)
Differential organization of synapses immunoreactive to phenylethanolamine-n-methyltransferase or neuropeptide Y in the parvicellular compartments of the hypothalamic paraventricular nucleus of the rat
Journal of Chemical Neuroanatomy
(1993)- et al.
Immunocytochemical evidence of stimulatory control by the ventral noradrenergic bundle of parvicellular neurons of the paraventricular nucleus secreting corticotropin-releasing hormone and vasopressin in rats
Brain Research
(1986) - et al.
The central organization of the vagus nerve innervating the colon of the rat
Gastroenterology
(1993) - et al.
In vitro brainstem-gastric preparation with intact vagi for study of primary visceral afferent input to dorsal vagal complex in caudal medulla
Journal of the Autonomic Nervous System
(1995) - et al.
Relays from the spinal cord and solitary nucleus through the parabrachial nucleus to the forebrain in the cat
Brain Research
(1990) - et al.
Prolactin-releasing peptide-immunoreactivity in A1 and A2 noradrenergic neurons of the rat medulla
Brain Research
(1999) - et al.
The relationship of efferent projections from the area postema to vagal motor and brain stem catecholamine-containing cell groups: an axonal transport and immunohistochemical study in the rat
Neuroscience
(1994) - et al.
The role of gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats
Gastroenterology
(2002) - et al.
Evidence that cholecystokinin induces immediate early gene expression in the brainstem, hypothalamus and amygdala of the rat by a CCKA receptor mechanism
Neuropharmacology
(1994) - et al.
Comparative study of dopamine- and noradrenaline-immunoreactive terminals in the paraventricular and supraoptic nuclei of the rat
Neuroscience Letters
(1987)
Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat
Brain Research Reviews
Calcitonin gene-related peptide and substance P in afferents to the upper gastrointestinal tract in the rat
Neuroscience Letters
The neuroanatomical axis for control of energy balance
Frontiers in Neuroendocrinology
Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis
Trends in Neuroscience
Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness
Frontiers in Neuroendocrinology
Most neurons in the nucleus tractus solitarii do not send collateral projections to multiple autonomic targets in the rat brain
Experimental Neurology
Feeding-induced c-fos expression in the nucleus of the solitary tract and dorsal medullary reticular formation in neonatal rats
Neuroscience Letters
Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat
Neuroscience
Synaptic inputs from the stomach to tuberoinfundibular neurons in the paraventricular nucleus of the hypothalamus in rats
Brain Research
Electrophysiological properties of neurons in the caudal ventrolateral medulla projecting to the paraventricular nucleus of the hypothalamus in rats
Brain Research
Adrenergic projection from the caudal part of the nucleus of the tractus solitarius to the parabrachial nucleus in the rat: immunocytochemical study combined with a retrograde tracing method
Brain Research
Neurons in the caudal ventrolateral medulla projecting to the paraventricular hypothalamic nucleus receive synaptic inputs from the nucleus of the solitary tract: a light and electron microscopic double-labeling study in the rat
Neuroscience Letters
Simultaneous monoaminehistofluorescence and neuropeptide immunocytochemistry: III. Ontogeny of catecholamine varicosities and neurophysin neurons in the rat supraoptic and paraventricular nuclei
Peptides
Neuropeptide Y modulation of A1 noradrenergic input to supraoptic vasopressin cells
Neuroscience Letters
Efferent projections from the parabrachial nucleus demonstrated with the anterograde tracer Phaseolus vulgaris leucoagglutinin
Brain Research Bulletin
A serotonin-containing pathway from the area postrema to the parabrachial nucleus in the rat
Neuroscience
Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in rat hypothalamus and brainstem
Neuroscience
The postnatal ontogeny of monoamine-containing neurones in the central nervous system of the albino rat
Brain Research
Capsaicin pretreatment attenuates multiple responses to cholecystokinin in rats
Journal of the Autonomic Nervous System
Inhibitory action of the ventral noradrenergic bundle on the lateral hypothalamic neurons through alpha-noradrenergic mechanisms in the rat
Brain Research
Electron microscopic examination of the catecholaminergic innervation of neurophysin- or vasopressin-containing neurons in the rat hypothalamus
Brain Research
Ultrastructural demonstration of dopamine-b-hydroxylase immunoreactive nerve terminals on vasopressin neurons in the paraventricular nucleus of the rat by double-labeling immunocytochemistry
Neuroscience Letters
Interconnections between the neuroendocrine hypothalamus and the central autonomic system
Frontiers in Neuroendocrinology
Further studies on the role of cholecystokinin-A and B receptors in secretion of anterior pituitary hormones in male rats
Neuropeptides
Maternal separation in neonatal rats elicits activation of the hypothalamic–pituitary–adrenocortical axis: a putative role for corticotropin-releasing factor
Psychoneuroendocrinology
Tracing of projection neurons from the cervical dorsal horn to the medulla with the anterograde tracer biotinylated dextran amine
Autonomic Neuroscience: Basic and Clinical
Adrenergic mechanisms in the control of corticotropin secretion
Journal of Endocrinology
Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts
Journal of Comparative Neurology
Expression of the glucagon-like peptide-1 receptor gene in rat brain
Journal of Neurochemistry
The bed nucleus of the stria terminalis: a target site for noradrenergic actions in opiate withdrawal
Annals of the New York Academy of Sciences
Cranial visceral afferent pathways through the nucleus of the solitary tract to caudal ventrolateral medulla or paraventricular hypothalamus: target-specific synaptic reliability and convergence patterns
The Journal of Neuroscience
Noradrenergic inputs to the bed nucleus of the stria teminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic–pituitary–adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine
The Journal of Neuroscience
Plasma hormone levels and central cFos expression in ferrets after systemic administration of cholecystokinin
American Journal of Physiology Regulatory Integrative and Comparative Physiology
Catecholamines, serotonin, acetylcholine, and g-aminobutyric acid in the rat brain: biochemical studies
The intrinsic organization of the central extended amygdala
Annals of the New York Academy of Sciences
A1 catecholamine cell group: fine structure and synaptic input from the nucleus of the solitary tract
Journal of Comparative Neurology
Vagus-post-pituitary reflex; antidiuretic effect
Clinical Journal of Physiology
Effect of excitatory amino acid on the hypothalamo-pituitary-adrenal axis in the rat during the stress-hyporesponsive period
Neuroendocrinology
Distributions of spinothalamic, spinohypothalamic, and spinotelencephalic fibers revealed by anterograde transport of PHA-L in rats
The Journal of Neuroscience
Development of the uptake and storage of L-[3H]norepinephrine in the rat brain
Journal of Neurochemistry
Cited by (79)
Skeletal interoception in bone homeostasis and pain
2022, Cell MetabolismParaventricular nucleus–Medullary interactions: How they help enable endocrine responses to metabolic stress
2022, Current Opinion in Endocrine and Metabolic ResearchGenetic Identification of Vagal Sensory Neurons That Control Feeding
2019, CellCitation Excerpt :This reveals that hypothalamic hunger circuits, which traditionally have been studied in the context of long-term nutritional signals such as leptin, also receive real-time information about the mechanical status of the gut. The ascending pathway that transmits this information from vagal mechanoreceptors to AgRP neurons is unknown, but it likely involves NTS neurons that project to the hypothalamus either directly (D’Agostino et al., 2016; Roman et al., 2017) or via a relay in the PBN (Rinaman, 2007; Roman et al., 2016). Indeed, we found that stimulation of Oxtr+ intestinal mechanoreceptors activated cells in the NTS and AP as well as their downstream target, the PBN, including two cell types that are known to inhibit food intake: Th+ neurons in the NTS and Calca+ neurons in the PBN.
Physiological feelings
2019, Neuroscience and Biobehavioral ReviewsFunctional neuroanatomy of peripheral inflammatory physiology: A meta-analysis of human neuroimaging studies
2018, Neuroscience and Biobehavioral ReviewsCentral regulation of energy metabolism by estrogens
2018, Molecular Metabolism