Autonomic effects induced by pharmacological activation and inhibition of Raphe Pallidus neurons in anaesthetized adult pigs

Systemic administration of dopamine (DA) receptor agonists leads to falls in body temperature. However, the central thermoregulatory pathways modulated by DA have not been fully elucidated. Here we identified a source and site of action contributing to DA's hypothermic action by inhibition of brown adipose tissue (BAT) thermogenesis. Nanoinjection of the type 2 and type 3 DA receptor (D2R/D3R) agonist, 7-OH-DPAT, in the rostral raphe pallidus area (rRPa) inhibits the sympathetic activation of BAT evoked by cold exposure or by direct activation of NMDA receptors in the rRPa. Blockade of D2R/D3R in the rRPa with nanoinjection of SB-277011A increases BAT thermogenesis, consistent with a tonic release of DA in the rRPa contributing to inhibition of BAT thermogenesis. Accordingly, D2R are expressed in cold-activated and serotonergic neurons in the rRPa and anatomical tracing studies revealed that neurons in the posterior hypothalamus (PH) are a source of dopaminergic input to the rRPa. Disinhibitory activation of PH neurons with nanoinjection of gabazine inhibits BAT thermogenesis, which is reduced by pre-treatment of the rRPa with SB-277011A. In conclusion, the rRPa, the site of sympathetic premotor neurons for BAT, receives a tonically-active, dopaminergic input from the PH that suppresses BAT thermogenesis.

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Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity

Nature Communications ◽

10.1038/s41467-021-25380-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xing Xiao ◽

Gagik Yeghiazaryan ◽

Simon Hess ◽

Paul Klemm ◽

Anna Sieben ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Homeostasis ◽

Raphe Nucleus ◽

Receptor Type ◽

Serotonergic Neurons ◽

Dynamic Regulation ◽

Brown Adipose ◽

Raphe Pallidus

AbstractThe wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.

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Raphe pallidus excites a unique class of sympathetic preganglionic neurons

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.1.r82 ◽

1993 ◽

Vol 265 (1) ◽

pp. R82-R89 ◽

Cited By ~ 13

Author(s):

S. F. Morrison

Keyword(s):

Splanchnic Nerve ◽

Short Latency ◽

Ventrolateral Medulla ◽

Conduction Time ◽

Antidromic Activation ◽

Sympathetic Preganglionic Neurons ◽

Preganglionic Neurons ◽

Long Latency ◽

Excitatory Responses ◽

Raphe Pallidus

The responses of splanchnic sympathetic preganglionic neurons (SPNs) to stimulation in raphe pallidus and in rostral ventrolateral medulla (RVLM) were compared to determine the basis for the excitatory responses evoked in the whole splanchnic preganglionic nerve bundle. Most (88%) of the SPNs with a short-latency (32 ms) excitatory response to RVLM stimulation were unaffected by raphe pallidus stimulation, although 12% were excited at a long latency (123 ms). Each of the SPNs with long-latency (114 ms) excitatory responses to RVLM stimulation was also excited by raphe pallidus stimulation at latencies (106 ms) that were 7 ms (P < 0.01) shorter than those evoked from the RVLM. Antidromic activation of raphe pallidus neurons from both the T8 intermediolateral nucleus (98 ms) and from the RVLM (18 ms) indicated that their spinally projecting axons emit collaterals (mean conduction time: 12 ms) into the ventrolateral medulla. In conclusion, the short-latency (70 ms) splanchnic nerve excitation evoked by RVLM stimulation is mediated primarily by SPNs that do not respond to raphe pallidus stimulation. Similarly, the long-latency (162 ms) splanchnic excitation evoked from the raphe pallidus is mediated primarily by SPNs that do not respond to the rapidly conducting sympathoexcitatory pathway from the RVLM. The long-latency (169 ms), RVLM stimulus-evoked excitation of the splanchnic nerve may arise from action potentials conducted on the axonal branches of raphe spinal neurons.

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Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.5.r1295 ◽

1995 ◽

Vol 268 (5) ◽

pp. R1295-R1302 ◽

Cited By ~ 14

Author(s):

M. J. Coleman ◽

R. A. Dampney

Keyword(s):

Arterial Pressure ◽

Sympathetic Activity ◽

Raphe Nuclei ◽

Ventrolateral Medulla ◽

Gamma Aminobutyric Acid ◽

Medullary Raphe ◽

Dose Dependent Decrease ◽

Raphé Nuclei ◽

Raphe Pallidus ◽

Dose Dependent

Microinjection of glutamate into sites within the medullary raphe nuclei (pallidus and obscurus) at levels caudal to the obex resulted in a dose-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate in anesthetized rabbits. The depressor and sympathoinhibitory responses were similar in magnitude to those elicited from the previously described depressor region in the caudal ventrolateral medulla (CVLM) but had a shorter duration, in both intact and barodenervated animals. The bradycardia was not altered by barodenervation but was reduced after administration of propranolol or atropine and abolished after administration of both drugs. The neuroinhibitory compounds gamma-aminobutyric acid or muscimol had no effect on MAP or RSNA when injected into the caudal medullary raphe nuclei but evoked a pressor and sympathoexcitatory response when injected into the CVLM. The results indicate that neurons within the caudal raphe pallidus and obscurus can powerfully inhibit sympathetic activity, but unlike sympathoinhibitory neurons in the CVLM, they are not tonically active and are not capable of producing sustained changes in arterial pressure and sympathetic activity.

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