Signalling routes and developmental regulation of group I metabotropic glutamate receptors in rat auditory midbrain neurons

Group I metabotropic glutamate receptors (mGluRs) are linked to intracellular Ca2+ signalling and play important roles related to synaptic plasticity and development. In neurons from the central nucleus of the inferior colliculus (CIC), the activation of these receptors evokes large [Ca2+]i responses. By using optical imaging of the fluorescent Ca2+-sensitive dye Fura-2, we have explored which [Ca2+]i routes are triggered by group I mGluR activation in young CIC neurons and whether mGluR-induced [Ca2+]i responses are regulated during postnatal development. In addition, real-time quantitative RT-PCR was used to study the developmental expression of both group I mGluR subtypes, mGluR1 and mGluR5. Application of DHPG, a specific agonist of group I mGluRs, was used on CIC slices from young rats to elicit [Ca2+]i responses. A majority of responses consisted of an initial thapsigargin-sensitive Ca2+ peak, related to store depletion, followed by a plateau phase, sensitive to the store-operated Ca2+ entry blocker 2-APB. During postnatal development, from P6 to P17, DHPG-induced [Ca2+]i responses changed. The largest Ca2+ responses were reached at P6, whereas lower peak and plateau responses were found after hearing onset, at P13P14 and P17. qRT-PCR analysis also revealed important differences in the expression of both mGluR1 and mGluR5 subtypes during development, with the highest levels of both subtypes at P7 and a developmental decrease of both transcripts. Our results suggest both intra- and extracellular routes for [Ca2+]i increases linked to group I mGluRs in CIC neurons and a regulation of group I mGluR activity and expression during auditory development. (c) 2012 Wiley Periodicals, Inc.