Periaqueductal gray matter projection to the parabrachial nucleus in rat

Abstract

The efferent projections from the periaqueductal gray matter (PAG) to the parabrachial nucleus (PB) were studied in the rat following microinjections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into restricted regions of the PAG. The dorsomedial and dorsolateral PAG columns project almost exclusively to the superior lateral PB subnucleus, whereas the lateral and ventrolateral PAG columns project to five lateral PB sites: dorsal lateral subnucleus, medial and lateral crescent areas (which flank the dorsal lateral PB subnucleus), central lateral subnucleus (rostral portion), and superior lateral subnucleus. The PAG region lying near the cerebral aqueduct projects to five lateral PB sites: external lateral subnucleus (inner subdivision), medial and lateral crescent areas, central lateral subnucleus (rostral portion), and dorsal lateral subnucleus. The internal lateral PB subnucleus, which projects exclusively to the intralaminar thalamic nuclei, and the Kölliker-Fuse nucleus were not innervated by the PAG. The PAG selectively innervates individual PB subnuclei that may be part of the spino-parachio-forebrain pathway. All PAG columns, including the aqueductal region, project to the superior lateral PB subnucleus, a presumed nociceptive relay site that receives inputs from multiple spinal cord regions (laminae I, V, and VIII) and projects to the ventromedial and retrochiasmatic hypothalamic areas-two regions that have been implicated in complex goal-directed behavior (e.g., food intake and reproductive function). Earlier studies demonstrated that the dorsal lateral and external lateral PB subnuclei (inner division) receive overlapping inputs from the superficial dorsal horn (laminae I and II) and the nucleus tractus solitarius, and both PB subnuclei send projections to limbic forebrain areas (e.g., hypothalamus, preoptic region, amygdala). Because the PAG projects to both of these PB subnuclei, this projection system possibly functions as a behavioral state-dependent filter system that modulates ascending nociceptive and/or visceral information as it is relayed through the PB to forebrain sites.

Midbrain modulation of the cardiac baroreflex involves excitation of lateral parabrachial neurons in the rat

“…Current evidence suggests that dorsolateral pontine-evoked modulation of the arterial baroreflex primarily originates from the ventrolateral regions of the LPBN and involves descending projections to both the NTS (9,24) and the RVLM (24)(25)(26)31). Yet, neuroanatomical data suggest that there are few direct projections from the dorsal PAG to the ventrolateral PBN (23). Instead, descending projections from the dorsal PAG primarily terminate in the central and superior lateral regions of the LPBN.…”

“…In a more recent study from our lab, utilizing smaller microinjection volumes, we confirmed that activation of lateral PBN (LPBN) neurons was essential for dorsal PAG evoked increases in MAP and heart rate (HR), as well as changes in breath timing (16). This observation corroborated neuroanatomical data showing that dorsal PAG neurons primarily project to the LPBN and not the medial PBN (23). Unexpectedly however, we demonstrated that bilateral blockade of LPBN area neurons with the GABA-A receptor agonist muscimol or the glutamate receptor antagonist kynurenic acid was approximately 20% more effective at attenuating dorsal PAG evoked increases in HR than changes in MAP.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…The thalamus is crucial in relaying nociceptive information via the ascending pain pathways and further projects onto the cortical regions which are involved in pain perception and emotional pain processing. The spinoparabrachial pathway is involved in the cognitive-affective dimension of pain as these neurons from the dorsal horn of the spinal cord project onto the parabrachial area, where they form synaptic connections with third order neurons that terminate in the ventral medial nucleus of the hypothalamus and the central nucleus of the amygdala (Bester et al, 1997;Derbyshire et al, 1997;Krout et al, 1998). The spinothalamic tract plays an important role in sympathetic and motivational responses to pain, as it projects onto the parabrachial nucleus and the PAG via the spinomesencephalic tract (Allen and Pronych, 1997;Jatsu Azkue et al, 1997;Keay et al, 1997).…”

“…The spinothalamic tract plays an important role in sympathetic and motivational responses to pain, as it projects onto the parabrachial nucleus and the PAG via the spinomesencephalic tract (Allen and Pronych, 1997;Jatsu Azkue et al, 1997;Keay et al, 1997). The PAG functions as a behavioural state-dependent relay station for modulation of both the descending and ascending pain pathways (Krout et al, 1998), and it also projects to the parabrachial nucleus which is known to be involved in emotional response to pain (Hunt and Mantyh, 2001;Lovick, 1996;Lumb and Lovick, 1993). …”

Neurokininergic Mechanism within the Lateral Crescent Nucleus of the Parabrachial Complex Participates in the Heart-Rate Response to Nociception

“…These include the lateral reticular formation, periaqueductal gray matter, and spinal trigeminal nucleus. All are innervated by spinal afferents, activated by noxious stimulation, and project to LPB (Cechetto et al, 1985;McMahon and Wall, 1985;Milner and Pickel, 1986;Herbert et al, 1990;Lanteri-Minet et al, 1994;Bernard et al, 1995;Craig, 1995;Feil and Herbert, 1995;Krout et al, 1998;Imbe et al, 1999;Keay and Bandler, 2002). However, it is not clear whether these projections contain substance P.…”