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J Neurophysiol 97: 3365-3375, 2007. First published March 21, 2007; doi:10.1152/jn.00686.2006
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Metabotropic Glutamate Receptors in the Lateral Superior Olive Activate TRP-Like Channels: Age- and Experience-Dependent Regulation

F. Aura Ene, Abigail Kalmbach and Karl Kandler

Department of Neurobiology and Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 3 July 2006; accepted in final form 11 March 2007

The lateral superior olive (LSO) is the primary auditory nucleus for processing of interaural sound level differences, which is one of the major cues for sound localization. During development, survival and maturation of LSO neurons critically depend on synaptic activity and intracellular calcium signaling. Before hearing onset, glutamatergic synaptic inputs from the cochlear nucleus (CN) to the LSO activate group I metabotropic glutamate receptors (mGluRs), which leads to calcium release from intracellular stores and large calcium influx from the extracellular milieu. Here, we investigated the nature of the mGluR-activated membrane channel that mediates the influx of extracellular calcium. Using Fura-2 calcium imaging in brain stem slices of neonatal and juvenile mice, we found that this calcium channel is blocked by Ni2+, La3+, and 2-aminoethoxydiphenylborane (2-APB), known antagonists of transient receptor potential (TRP) channels. During postnatal development, the contribution of extracellular calcium influx to mGluR-mediated Ca2+ responses gradually decreased and was almost abolished by the end of the third postnatal week. Over this period, the contribution of Ca2+ release from internal stores remained unchanged. The developmental decrease of TRP-like channel-mediated calcium influx was significantly less in congenitally deaf waltzer mice, suggesting that early auditory experience is necessary for the normal age-dependent downregulation of functional TRP channels.


Address for reprint requests and other correspondence: K. Kandler, Department of Neurobiology, University of Pittsburgh School of Medicine, Biomedical Science Tower W1457, 3500 Terrace Street, Pittsburgh, PA 15261 (E-mail: kkarl{at}pitt.edu)







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