Immunocytochemical studies of the 5-HT1A receptor in ventral medullary neurons that project to the intermediolateral cell column and contain serotonin or tyrosine hydroxylase immunoreactivity

Abstract

Activation of serotonin-1A receptors (5-HT(1A)R) in the medulla oblongata lowers sympathetic nerve discharge and blood pressure. Binding sites for 5-HT(1A)R ligands are present in ventral medullary nuclei [e.g., rostral ventrolateral medulla (RVLM), raphe pallidus (RPa), and parapyramidal region (PPR)] that project to sympathetic preganglionic neurons in the intermediolateral cell column (IML). However, the projections and the neurochemical contents of the ventral medullary neurons that are likely to be involved in the hypotensive actions of 5-HT(1A) agonists are unclear. Using a sheep antibody to a fragment of the third intracellular loop of the 5-HT(1A)R, we localized 5-HT(1A)R immunoreactivity (ir) to IML-projecting neurons that were retrogradely labeled with rhodamine beads injected into the IML of adult male rats. The percentages of IML-projecting neurons containing 5-HT(1A)R-ir were 49% in RPa, 34% in PPR, and 44% in RVLM. Using multiple-immunofluorescence labeling, we also demonstrated 5-HT(1A)R-ir in serotonergic (5-HT) and in catecholaminergic (tyrosine hydroxylase; TH-ir) neurons of the ventral medulla. The percentages of 5-HT-ir neurons containing 5-HT(1A)R-ir were 28% in RPa, 18% in PPR, and 31% in raphe obscurus. In addition, 5-HT(1A)R-ir was present in 14% of TH-ir neurons of the RVLM. Moreover, some IML-projecting neurons in the PPR and RPa were doubly immunolabeled for 5-HT(1A)R-ir and 5-HT, and some IML-projecting neurons in the RVLM were doubly immunolabeled for 5-HT(1A)R-ir and TH-ir. These data provide anatomical evidence for the presence of 5-HT(1A)R on serotonergic and catecholaminergic bulbospinal neurons and for their potential role in directly modifying the activity of these ventral medullary neurons.

Central efferent pathways for cold‐defensive and febrile shivering

“…Activation of 5‐HT 1A receptors in the rostral medullary raphe region eliminated shivering responses to skin cooling and to PGE 2 injection into the MPO. The 5‐HT 1A receptor is negatively coupled to adenylate cyclase via G i proteins probably leading to inhibition of neuronal functions (Barnes & Sharp, 1999) and these receptors are located on spinal‐projecting neurons in the medullary raphe region (Helke et al 1997), consistent with the potential localization of 5‐HT 1A receptors on the cell bodies of putative shivering‐mediating premotor neurons in the rRPa. Application of 8‐OH‐DPAT in the piglet medullary raphe or in the lateral paragigantocellular nucleus attenuated cooling‐evoked shivering (Hoffman et al 2007; Brown et al 2008), although the time course of the microdialysis application allowed for the possibility that the 8‐OH‐DPAT applied in the lateral paragigantocellular nucleus diffused into the rostral medullary raphe region to inhibit shivering.…”

Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response

“…Consequently, genetic loss or pharmacological block of SERT at multiple sites within the CNS could ultimately alter the excitability (increase or decrease) of sympathetic preganglionic neurons. For example, 5-HT can act directly within the RVLM to inhibit the sympathetic premotor neurons, likely via 5-HT 1A receptors, although excitation via 5-HT 2 receptors has been reported 47-51 . Altered SERT function could also have less direct effects on the excitability of RVLM neurons by modulating input from other brain regions.…”

5‐HT1A RECEPTORS IN STRESS‐INDUCED CARDIAC CHANGES: A POSSIBLE LINK BETWEEN MENTAL AND CARDIAC DISORDERS

“…This brain stem region also represents the major source of descending 5‐HT projections to the spinal sympathetic neurons. Many bulbospinal neurons located in the raphe/parapyramidal area are serotonergic and express inhibitory 5‐HT 1A autoreceptors on their perikarya and dendrites 45 . Retrograde viral tracing revealed that this same area contains presympathetic cardiomotor neurons; 17 their neurotransmitter phenotype is currently unknown.…”