Hypothalamic Control of the Autonomic Nervous System
Other than a relatively modest projection to the pre-ganglionic neurons from the infralimbic cortex, the hypothalamus is the highest level of the neuraxis that provides substantial input to the autonomic nervous system. It regulates virtually all autonomic functions and coordinates them with each other, and with ongoing behavioral, metabolic, and emotional activity. The hypothalamus contains several sets of neurons, using different neurotransmitters, that provide innervation to the sympathetic and parasympathetic preganglionic neurons, as well as brainstem areas that regulate the autonomic nervous system. Many of these neurons are in the paraventricular nucleus of the hypothalamus. These form populations of small neurons that are typically dorsal or ventral to the main endocrine groups, and most of the paraventricular-autonomic neurons contain messenger ribonucleic acid (mRNA) for either oxytocin or vasopressin. The descending pathways also stain immunohistochemically for these peptides and are probably involved in stress responses.
A second set of
hypothalamic-autonomic neurons is found in the lateral hypothalamic area. These
consist mainly of neurons containing orexin or melanin-concentrating hormone
(MCH) neurons, and some-times the peptide cocaine- and amphetamine-regulated
transcript (CART), which is thought to be involved in regulation of feeding and
metabolism as well as wake-sleep and locomotor activity. A third population of
hypothalamic-autonomic cells is found in the arcuate nucleus and adjacent
retrochiasmatic area. These neurons contain α-melanocyte–stimulating hormone and CART and may also be involved in
feeding and metabolic regulation.
All three sets
of neurons send axons to the brainstem, where they innervate the nucleus of the
solitary tract (which receives visceral afferent input from the glos-sopharyngeal
and vagus nerves), as well as the regions that coordinate autonomic and
respiratory reflexes in the ventrolateral medulla. Other axons innervate the
parasympathetic preganglionic neurons in the Edinger-Westphal nucleus
(pupillary constriction), the superior salivatory nucleus (associated with the
facial nerve, which supplies the submandibular and sublingual salivary glands
as well as the cerebral vasculature), the inferior salivatory nucleus
(associated with the rostral tip of the nucleus of the solitary tract,
supplying the parotid gland), the dorsal motor vagal nucleus (which supplies
the abdominal organs), and the nucleus ambiguus (which is the main source of
vagal input to the thoracic organs, including the esophagus, heart, and lungs).
Finally, there
are descending axons from the hypothalamus that innervate the sympathetic
preganglionic neurons in the thoracic spinal cord. Different populations of
hypothalamospinal neurons contact distinct targets. For example, the main
projection from the orexin neurons is to the upper thoracic spinal cord, which
may be important for autonomic functions associated with ingestion. The
oxytocin neurons innervate specific clusters of sympathetic preganglionic
neurons at multiple spinal cord levels.
In addition,
there is a major input to the medullary raphe nuclei from the preoptic area and
dorsomedial nucleus of the hypothalamus. The medullary raphe nuclei contain
both serotoninergic and glutamatergic neurons that innervate the sympathetic
preganglionic column at multiple levels and regulate populations of neurons
involved in thermoregulation. This pathway is thought to be a major mechanism
for regulating body temperature.
Damage to the descending hypothalamic-autonomic pathway, in the lateral medulla or spinal cord, causes an ipsilateral central Horner syndrome. Such patients not only have a small pupil and ptosis on that side but lack sweating on the affected side of the face and body.
