DEVELOPING NEONATAL RAT SYMPATHETIC AND SENSORY NEURONS DIFFER IN THEIR REGULATION OF 5-HT3 RECEPTOR EXPRESSION

Serotonin 5-HT3 receptors (5-HT(3)Rs) are ligand-gated ion channels ex pressed by many peripheral neurons and are involved in several physiol ogical processes. To learn more about the developmental regulation of 5-HT3R expression, we investigated rat sympathetic and vagal sensory n eurons. We found that sympathetic and sensory neurons differ in their regulation of 5-HT3R expression during early postnatal life and as the se 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 in crease occurs even after elimination of preganglionic innervation. In comparison, 5-HT3R mRNA levels in P1 nodose neurons are over 14-fold g reater than in P1 SCG and change little by P21. We show that 5-HT3R tr anscript 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 incre ase for neurons developing for 7 d in vivo, 117 contrast, 5-HT3R mRNA levels in cultured nodose neurons arop by 70% within 24 hr; however, t his drop is transient, After 2 d, transcript levels begin to increase, and after 7 d, they are above initial values, We show that this delay ed increase in 5-HT3R expression depends on neurotrophins. In both nod ose and sympathetic neurons we found that the changes in 5-HT3R gene e xpression correlate directly with the appearance of 5-HT-evoked curren t densities.