Developmental changes in metabotropic glutamate receptor-mediated calcium homeostasis

Neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), requir e eighth nerve activation of metabotropic glutamate receptors (mGluRs) for maintenance of intracellular calcium homeostasis. Interrupting this activat ion results in an increase in intracellular calcium concentration ([Ca2+](i )) followed by cell atrophy, degeneration, and death of many neurons. Altho ugh these phenomena are well characterized in late embryonic and posthatch chicks, little is known about the role of mGluRs and calcium homeostasis du ring the development of synaptic activity in NM. Using Fura-2 imaging, fluo rescent immunohistochemistry, and Western immunoblotting, we investigated ( 1) the expression and function of group I mGluRs and their role in calcium regulation during development of NM, and (2) the expression of two other ke y molecules involved in regulating neuronal [Ca2+](i) : inositol trisphosph ate receptors (IP(3)Rs) and sarcoplasmic/endoplasmic reticulum calcium ATPa ses (SERCAs). Confocal imaging of Fluo-3-labeled NM was used to investigate the kinetics of global NM neuron calcium signals. Measurements were made a t four ages that extend from before synaptic function begins in NM, through functional onset, to mature patterns of spontaneous activity, namely, embr yonic days (E) 10, 13, 15, and 18. mGluR5, mGluR1, and SERCA expression pea ked at E13 and then decreased with age. IP3R expression increased to peak a t E18. [Ca2+](i) response to mGluR activation increased with age. The rise time of [Ca2+](i) signals in NM neurons did not change with development, bu t E13 neurons were slower to reestablish baseline [Ca2+](i). These results suggest that the mGluR-mediated calcium homeostasis of NM neurons develops in parallel with synaptic activity and appears to be refined with increasin g synaptic activity. J. Comp. Neurol. 421:95-106, 2000. (C) 2000 Wiley-Liss , Inc.