Developing Neonatal Rat Sympathetic and Sensory Neurons Differ in Their Regulation of 5-HT3Receptor Expression

Abstract

Serotonin 5-HT3 receptors (5-HT3Rs) are ligand-gated ion channels expressed by many peripheral neurons and are involved in several physiological processes. To learn more about the developmental regulation of 5-HT3R expression, we investigated rat sympathetic and vagal sensory neurons. We found that sympathetic and sensory neurons differ in their regulation of 5-HT3R expression during early postnatal life and as these neurons develop in culture. In SCG neurons 5-HT3R transcript levels are low at postnatal day 1 (P1) and increase 7.5-fold by P21; this increase occurs even after elimination of preganglionic innervation. In comparison, 5-HT3R mRNA levels in P1 nodose neurons are over 14-fold greater than in P1 SCG and change little by P21. We show that 5-HT3R transcript levels in nodose neurons depend on intact target innervation and drop by 60% after axotomy. When P1 SCG neurons develop in culture, we observed a significant increase in 5-HT3R expression: after 7 d in culture, transcript levels increase ninefold versus a threefold increase for neurons developing for 7 d in vivo. In contrast, 5-HT3R mRNA levels in cultured nodose neurons drop by 70% within 24 hr; however, this drop is transient. After 2 d, transcript levels begin to increase, and after 7 d, they are above initial values. We show that this delayed increase in 5-HT3R expression depends on neurotrophins. In both nodose and sympathetic neurons we found that the changes in 5-HT3R gene expression correlate directly with the appearance of 5-HT-evoked current densities.