Structure

The main parabrachial nuclei are the medial parabrachial nucleus, the lateral parabrachial nucleus, and the subparabrachial nucleus. They are located at the junction of the midbrain and pons.^[4]

Afferents and efferents

The parabrachial nuclei receive visceral afferent information from a variety of sources in the brainstem, including much from the solitary nucleus, which brings taste information and information about the remainder of the body.^[5]

The external, dorsal, internal and superior lateral subnuclei also receive input from the spinal and trigeminal dorsal horn, mainly concerned with pain and other visceral sensations.^[6]

Outputs from the parabrachial nucleus originate from specific subnuclei and target forebrain sites involved in autonomic regulation, including the lateral hypothalamic area, ventromedial, dorsomedial, and arcuate hypothalamic nuclei, the median and lateral preoptic nuclei, the substantia innominate, the ventroposterior parvicellular and intralaminar thalamic nuclei, the central nucleus of the amygdala, and the insular and infralimbic cortex.^[2]

The subparabrachialnucleus and lateral crescent send efferents to the nucleus of the solitary tract, ventrolateral medulla, and spinal cord, where they target many respiratory and autonomic cell groups.^[3] Many of these same brainstem and forebrain areas send efferents back to the parabrachial nucleus as well.^[7][5]

Arousal

Many subsets of neurons in the parabrachial complex that target specific forebrain or brainstem cell groups contain specific neuropeptides,^[8] and appear to carry out distinct functions. For example, a population of neurons in the external lateral parabrachial subnucleus that contain the neurotransmitter calcitonin gene-related peptide (CGRP) appears to be critical for relaying information about hypoxia (low blood oxygen) and/or hypercapnia (high blood CO₂) to forebrain sites to “wake up the brain” (arouse) when breathing is inadequate to meet physiological demands during sleep. This resulting “wakefulness drive to breath” contributes to prevention of asphyxia.^[9]

Recent data indicate that glutamatergic neurons in the medial and lateral parabrachial nuclei, along with glutamatergic neurons in the pedunculopontine tegmental nucleus, provide a critical node in the brainstem for producing a waking state.^[10][11] Lesions of these neurons cause irreversible coma.

Blood sugar control

Other neurons in the superior lateral parabrachial nucleus that contain cholecystokinin have been found to prevent hypoglycemia.^[12]

Thermoregulation

In 2008, neurons in the external lateral parabrachial nucleus were found to mediate cold sensory transmission from the skin to the preoptic area, a thermoregulatory center in the hypothalamus, to stimulate heat production in the cold.^[13] Warm sensory transmission to the preoptic area to avoid hyperthermia in hot environments is mediated by another group of neurons in the dorsal lateral parabrachial nucleus,^[14] which contain dynorphin or cholecystokinin.^[15][16][17]

A study in 2017, has shown this thermosensory information to be relayed through the lateral parabrachial nucleus rather than the thalamus, which drives thermoregulatory behavior.^[18][19] A thermosensory neural pathway from the lateral parabrachial nucleus to the preoptic area induces heat avoidance behavior, and another pathway to the central amygdaloid nucleus induces cold avoidance behavior.^[20]

Taste

Parabrachial neurons in rodents that relay taste information to the ventroposterior parvocellular (taste) nucleus of the thalamus are mainly CGRP neurons in the external medial parabrachial nucleus and they project predominantly contralaterally, as well as a smaller number in the ventral lateral nucleus, which project mainly ipsilaterally.^[21]

Neurons that mediate the sensation of itching, connect to the parabrachial nucleus by way of glutamatergic spinal projection neurons. This pathway triggers scratching in mice.^[22]

Pleasure

The parabrachial nucleus relays satiety and pain-related signals to higher brain regions; when inhibited, this can produce "liking" responses to certain pleasurable stimuli, such as sweet taste.^[23]

Wet dog shakes

The lateral parabrachial nucleus integrates sensory signals, primarily, but not exclusively, from low-threshold mechanoreceptors to initiate the wet dog shake behavior by which mammals remove water and irritants from their back and neck fur. It receives this mechanoreceptor input from group C nerve fibers that connect to spinoparabrachial neurons in the spinal cord.^[24]