PT  - JOURNAL ARTICLE
AU  - Edmund M. Talley
AU  - Negar N. Sadr
AU  - Douglas A. Bayliss
TI  - Postnatal Development of Serotonergic Innervation, 5-HT<sub>1A</sub> Receptor Expression, and 5-HT Responses in Rat Motoneurons
AID  - 10.1523/JNEUROSCI.17-11-04473.1997
DP  - 1997 Jun 01
TA  - The Journal of Neuroscience
PG  - 4473--4485
VI  - 17
IP  - 11
4099  - http://www.jneurosci.org/content/17/11/4473.short
4100  - http://www.jneurosci.org/content/17/11/4473.full
SO  - J. Neurosci.1997 Jun 01; 17
AB  - We compared the electrophysiological responses to serotonin (5-HT) of neonatal and juvenile rat hypoglossal motoneurons (HMs) by using intracellular recording techniques in a brainstem slice preparation. In neonatal HMs (≤P8), 5-HT caused a substantial decrease in the amplitude of spike afterhyperpolarization (AHP) that was associated with an increase in the minimal repetitive firing frequency (Fmin). Previous work has shown that this effect of 5-HT was mediated by the 5-HT1A receptor and may be secondary to inhibition of N- and P/Q-type calcium channels. In contrast to results from neonates, we found that 5-HT did not inhibit the AHP in juvenile HMs (≥ P20). Application of a cocktail of calcium channel toxins (ω-Conotoxin-GVIA and ω-Agatoxin-IVA) to juvenile HMs substantially inhibited the AHP, indicating that calcium entry through N- and P/Q-type channels supports the AHP in juvenile HMs, as it does in neonates. In addition, intracellular injection of the long-lasting GTP analog GTPγS induced an agonist-independent increase in Fmin similar to that seen in neonates in the presence of 5-HT. Together, these results suggested that intracellular mechanisms downstream of the 5-HT1A receptor capable of inhibiting the AHP were intact in juvenile HMs. Therefore, we investigated the possibility that age-related changes in effects of 5-HT on the AHP resulted from altered expression of the 5-HT1A receptor. To this end, we performed ligand-binding autoradiography using [3H]8-OH-DPAT, a 5-HT1Aagonist, and in situ hybridization using radiolabeled oligonucleotide probes specific for the 5-HT1A receptor. The two approaches gave remarkably similar results. The highest levels of 5-HT1A receptor expression were found in neonatal HMs, with maximal binding and hybridization at approximately postnatal day 7 (P7) and only low levels of receptor expression by P28. Finally, immunohistochemistry for 5-HT revealed that these developmental changes in 5-HT1A receptor expression occurred coincident with a postnatal increase in serotonergic innervation of the hypoglossal nucleus (nXII). Together, these findings indicate that developmental changes occur in the serotonergic innervation of nXII and in the expression of 5-HT1A receptors in HMs during the early postnatal period, resulting in markedly different effects of 5-HT on firing behavior in neonatal and juvenile HMs.