Brain sources of inhibitory input to the rat rostral ventrolateral medulla

Abstract

The rostral ventrolateral medulla (RVLM) contains neurons critical for cardiovascular, respiratory, metabolic, and motor control. The activity of these neurons is controlled by inputs from multiple identified brain regions; however, the neurochemistry of these inputs is largely unknown. Gamma-aminobutyric acid (GABA) and enkephalin tonically inhibit neurons within the RVLM. The aim of this study was to identify all brain regions that provide GABAergic or enkephalinergic input to the rat RVLM. Neurons immunoreactive for cholera toxin B (CTB-ir), retrogradely transported from the RVLM, were assessed for expression of glutamic acid decarboxylase (GAD67) or preproenkephalin (PPE) mRNA using in situ hybridization. GAD67 mRNA was expressed in CTB-ir neurons in the following regions: the nucleus of the solitary tract (NTS, 6% of CTB-ir neurons), area postrema (AP, 8%), caudal ventrolateral medulla (17%), midline raphe (40%), ventrolateral periaqueductal gray (VLPAG, 15%), lateral hypothalamic area (LHA, 25%), central nucleus of the amygdala (CeA, 77%), sublenticular extended amygdala (SLEA, 86%), interstitial nucleus of the posterior limb of the anterior commissure (IPAC, 56%), bed nucleus of the stria terminals (BNST, 59%), and medial preoptic area (MPA, 53%). PPE mRNA was expressed in CTB-ir neurons in the following regions: the NTS (14% of CTB-ir neurons), midline raphe (26%), LHA (22%), zona incerta (ZI, 15%), CeA (5%), paraventricular nucleus (PVN, 13%), SLEA (66%), and MPA (26%). Thus, limited brain regions contribute GABAergic and/or enkephalinergic input to the RVLM. Multiple neurochemically distinct pathways originate from these brain regions projecting to the RVLM.

Circumventricular Organs

“…There are few, if any, connections to the dorsal motor nucleus of the vagus, but it has been suggested that some area postrema connections within the nucleus of the solitary tract are terminating on dendrites of vagal motor neurons, having cell bodies in the vagal motor nucleus (Shapiro and Miselis, 1985). Other medullary targets of the area postrema efferents are the rostral ventrolateral medulla (Blessing et al, 1987;Bowman et al, 2013), the dorsal aspect of the spinal trigeminal tract and nucleus and the paratrigeminal nucleus (Shapiro and Miselis, 1985); although Cunningham et al (1994) did not confirm these last two projections in a later study. The most prominent efferent projection of the area postrema outside the medulla is to the dorsal pontine region, the target of these fibers being the middle third of the lateral parabrachial nucleus (van der Kooy and Koda, 1983; Shapiro IV.…”

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function

“…In-situ hybridization for custom synthesized and validated prepro-enkephalin (PPE) riboprobe incorporated with digoxigenin (DIG)-11-UTP (Roche Applied Science, Mannheim, Germany) was performed (final concentration 1000 ng/ml) in conjunction with fluorescent immunohistochemical (IHC) detection as described previously (Bowman et al, 2013;Kumar et al, 2010;Parker et al, 2013). No alkaline phosphatase reaction product is seen after hybridization with our PPE mRNA sense probe, or in the absence of antisense DIGriboprobes in rat spinal cord tissue (Kumar et al, 2010;Parker et al, 2013).…”

Sympathoexcitation and pressor responses induced by ethanol in the central nucleus of amygdala involves activation of NMDA receptors in rats

“…Second, other studies have reported that chemical lesions of the CeA in spontaneous hypertensive rats delay the development of hypertension (48) and attenuate cardiovascular responses to acute stress in rats with borderline hypertension (47). Most importantly, anatomic and electrophysiological studies (6,17,45,46) have identified CeA neurons that have axons projecting to presympathetic neurons in the rostral ventrolateral medulla (RVLM). The RVLM provides a key source of excitatory drive to sympathetic preganglionic neurons in the spinal cord regulating the sympathetic nervous system; therefore, it is reasonable to speculate that CeA is one of the key nuclei that plays an important role in the control of sympathetic outflow and AP in response to ethanol challenge.…”