Article

5-HT2C-like receptors in the brain of Xenopus laevis initiate sex-typical fictive vocalizations.

Department of Biology, Boston University, Boston, Massachusetts 02215, USA.
Journal of Neurophysiology (impact factor: 3.32). 06/2009; 102(2):752-65. DOI:10.1152/jn.90469.2008 pp.752-65
Source: PubMed

ABSTRACT Vocalizations of male and female African clawed frogs (Xenopus laevis) are generated by brain stem central pattern generators. Serotonin (5-HT) is likely important for vocal initiation because, when applied in vitro, sex-typical fictive vocalizations are evoked from isolated brains. To explore the mechanisms underlying vocal initiation, we identified the types of serotonin receptors mediating vocal activation pharmacologically using a whole brain, fictive preparation. The results showed that 5-HT(2C)-like receptors are important for activation of fictive vocalizations in the sexes. 5-HT(2C) receptor agonists elicited fictive vocalizations, and 5-HT(2C) receptor antagonists blocked 5-HT-induced fictive vocalizations, whereas agonists and antagonists of 5-HT(2A) and 5-HT(2B) receptors failed to initiate or block 5-HT-induced fictive vocalizations in the sexes. The results indicate that serotonin initiates fictive vocalizations by binding to 5-HT(2C)-like receptors located either within or upstream of the vocal central pattern generator in both sexes. We conclude that the basic mechanism of vocal initiation is shared by the sexes despite the differences in the actual vocalizations between males and females. Sex-typical vocalizations, therefore, most likely arise from activation of different populations of 5-HT(2C) receptor expressing cells or from differential activation of downstream pattern generating neurons.

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  • Article: Voltage oscillations in Xenopus spinal cord neurons: developmental onset and dependence on co-activation of NMDA and 5HT receptors.
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    ABSTRACT: The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 microM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2-5 microM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT1alpha receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a selective 5HT1alpha receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4-8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an 'apparent' decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg2+ block. When the membrane potential was depolarized by approximately 20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1alpha-like pharmacology.
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Keywords

5-HT(2C)-like receptors
 
5-HT-induced fictive vocalizations
 
actual vocalizations
 
antagonists
 
block 5-HT-induced fictive vocalizations
 
central pattern generators
 
different populations
 
differential activation
 
downstream pattern
 
female African clawed frogs
 
fictive preparation
 
fictive vocalizations
 
serotonin initiates fictive vocalizations
 
serotonin receptors mediating vocal activation pharmacologically
 
sex-typical fictive vocalizations
 
Sex-typical vocalizations
 
vocal central pattern generator
 
vocal initiation
 
Vocalizations
 
whole brain
 

Heather J Yu