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 Ca(2+) 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 [Ca(2+) ](i) responses. By using optical imaging of the fluorescent Ca(2+) -sensitive dye Fura-2, we have explored which [Ca(2+) ](i) routes are triggered by group I mGluR activation in young CIC neurons and whether mGluR-induced [Ca(2+) ](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 [Ca(2+) ](i) responses. A majority of responses consisted of an initial thapsigargin-sensitive Ca(2+) peak, related to store depletion, followed by a plateau phase, sensitive to the store-operated Ca(2+) entry blocker 2-APB. During postnatal development, from P6 to P17, DHPG-induced [Ca(2+) ](i) responses changed. The largest Ca(2+) responses were reached at P6, whereas lower peak and plateau responses were found after hearing onset, at P13-P14 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 [Ca(2+) ](i) increases linked to group I mGluRs in CIC neurons and a regulation of group I mGluR activity and expression during auditory development.
Instituto de Investigación en Discapacidades Neurológicas/Medical School, Universidad de Castilla-La Mancha, Albacete, Spain. juanramon.martinez@uclm.es
Juan R
JR
Martinez-Galan
Francisco C
FC
Perez-Martinez
Jose M
JM
Juiz
D000375:Aging / Q000502:physiology; D000818:Animals; D001303:Auditory Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D015220:Calcium Channels; D018076:DNA, Complementary; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; D012313:RNA; D015544:Inositol 1,4,5-Trisphosphate; C010117:3,4-dihydroxyphenylglycol