Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

Abstract

Ootsuka, Youichirou, and William W. Blessing. Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit. Am J Physiol Regul Integr Comp Physiol 288: R909 -R918, 2005. First published November 18, 2004; doi:10.1152/ajpregu.00564. 2004.-Neurons in the rostral medullary raphé/parapyramidal region regulate cutaneous sympathetic nerve discharge. Using focal electrical stimulation at different dorsoventral raphé/parapyramidal sites in anesthetized rabbits, we have now demonstrated that increases in ear pinna cutaneous sympathetic nerve discharge can be elicited only from sites within 1 mm of the ventral surface of the medulla. By comparing the latency to sympathetic discharge following stimulation at the ventral raphé site with the corresponding latency following stimulation of the spinal cord [third thoracic (T3) dorsolateral funiculus] we determined that the axonal conduction velocity of raphé-spinal neurons exciting ear pinna sympathetic vasomotor nerves is 0.8 Ϯ 0.1 m/s (n ϭ 6, range 0.6 -1.1 m/s). Applications of the 5-hydroxytryptamine (, 80 g/kg in 0.8 ml) to the cerebrospinal fluid above thoracic spinal cord (T1-T7), but not the lumbar spinal cord (L2-L4), reduced raphé-evoked increases in ear pinna sympathetic vasomotor discharge from 43 Ϯ 9 to 16 Ϯ 6% (P Ͻ 0.01, n ϭ 8). Subsequent application of the excitatory amino acid (EAA) antagonist kynurenic acid (25 mol in 0.5 ml) substantially reduced the remaining evoked discharge (22 Ϯ 8 to 6 Ϯ 6%, P Ͻ 0.05, n ϭ 5). Our conduction velocity data demonstrate that only slowly conducting raphé-spinal axons, in the unmyelinated range, contribute to sympathetic cutaneous vasomotor discharge evoked by electrical stimulation of the medullary raphé/parapyramidal region. Our pharmacological data provide evidence that raphé-spinal neurons using 5-HT as a neurotransmitter contribute to excitation of sympathetic preganglionic neurons regulating cutaneous vasomotor discharge. Raphé-spinal neurons using an EAA, perhaps glutamate, make a substantial contribution to the ear sympathetic nerve discharge evoked by raphé stimulation.5-hydroxytryptamine2A receptors; kynurenic acid; SR-46349B; sympathetic preganglionic neuron; cutaneous blood flow NEURONS IN THE ROSTRAL MEDULLARY raphé/parapyramidal region regulate cutaneous vasomotor tone by controlling cutaneous sympathetic preganglionic neuronal activity (7,39,42,45). Identification and characterization of the relevant neurons is an important task. Activity of these neurons contributes to the heat exchange aspect of thermoregulation as well as to the integrated bodily response to nociceptive or salient environmental events (7,21,35,36,39,42,45,49). Neuroanatomic studies using transneuronal transport of live virus injected into the tail vasculature indicate that a proportion of sympathetic premotor raphé-spinal neurons synthesize serotonin (5-hydroxytryptamine, 5-HT) (32, 44).Although 5-HT is a neurotransmitter traditionally considered...

Central circuitries for body temperature regulation and fever

“…7G) (101) and that nanoinjection of glutamate or NMDA into similar spinal sites elicits BAT thermogenesis (84,101). Furthermore, cutaneous sympathetic nerve discharge evoked by stimulation of the rMR was eliminated by spinal application of an antagonist for excitatory amino acid receptors (123). These findings indicate that the glutamatergic pathway from the rMR to the IML is an essential component of the premotor signaling that controls BAT thermogenesis and cutaneous vasoconstriction (Fig.…”

“…Consistent with this idea, blockade of serotonin receptors in the IML attenuates cooling-evoked BAT thermogenesis, and this attenuation is ascribable to blockade of 5-HT 1A and 5-HT 7 receptors in the IML (80). Raphe-spinal serotonergic signaling is also involved in the regulation of cutaneous vasomotion through 5-HT 2A receptors in the spinal cord, as evidenced by a physiological study in which CVC sympathetic nerve discharge evoked by stimulation of the rMR was reduced by spinal application of a 5-HT 2A receptor antagonist (123). In further support of the significant role of serotonergic neurons in cold defense, mice whose central serotonergic neurons are almost all eliminated show blunted BAT thermogenic and shivering responses to intense cold exposure (53) and acute inhibition of central serotonergic neurons transiently lowers body temperature under room temperature (135).…”

Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction

“…Having established that neurons in the same DMH locus as those required for BAT SNA responses were not necessary for tail CVC responses, we sought to determine whether the activity of neurons in the rRPa, a locus of sympathetic premotor neurons for CVC drive (2,39,41,58), is necessary for the activation of tail CVC neurons evoked by PGE 2 into the POA by observing the effect on tail CVC neuronal discharge (n ϭ 9 CVC neurons) of muscimol into the rRPa subsequent to PGE 2 into the POA. These rats had received prior bilateral nanoinjections of muscimol into the DMH that were without effect on the neuronal activation elicited by PGE 2 into the POA (Figs.…”

“…7, C and D). The rRPa injection sites were located within the region of the rostral ventromedial medulla containing putative sympathetic premotor neurons necessary for activation of cutaneous vasoconstriction (39,41,58) and BAT thermogenesis (3,29,30,34,35).…”

Serotonin and Blood Pressure Regulation

“…Intravenous administration of a 5-HT 2A -receptor agonist facilitates the cutaneous sympathetic outflow (Blessing and Seaman, 2003), potentially at the IML site of sympathetic preganglionic neurons (Ootsuka and Blessing, 2005), and thus could contribute to an elevated arterial pressure in response to central 5-HT 2A -receptor agonist administration.…”