Developmental changes in metabotropic glutamate receptor–mediated calcium homeostasis

Abstract

Neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), require eighth nerve activation of metabotropic glutamate receptors (mGluRs) for maintenance of intracellular calcium homeostasis. Interrupting this activation results in an increase in intracellular calcium concentration ([Ca(2+)](i)) followed by cell atrophy, degeneration, and death of many neurons. Although these phenomena are well characterized in late embryonic and posthatch chicks, little is known about the role of mGluRs and calcium homeostasis during the development of synaptic activity in NM. Using Fura-2 imaging, fluorescent 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 key molecules involved in regulating neuronal [Ca(2+)](i) : inositol trisphosphate receptors (IP(3)Rs) and sarcoplasmic/endoplasmic reticulum calcium ATPases (SERCAs). Confocal imaging of Fluo-3-labeled NM was used to investigate the kinetics of global NM neuron calcium signals. Measurements were made at four ages that extend from before synaptic function begins in NM, through functional onset, to mature patterns of spontaneous activity, namely, embryonic days (E) 10, 13, 15, and 18. mGluR5, mGluR1, and SERCA expression peaked at E13 and then decreased with age. IP(3)R expression increased to peak at E18. [Ca(2+)](i) response to mGluR activation increased with age. The rise time of [Ca(2+)](i) signals in NM neurons did not change with development, but E13 neurons were slower to reestablish baseline [Ca(2+)](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 increasing synaptic activity.

Activity‐dependent synaptic integration and modulation of bilateral excitatory inputs in an auditory coincidence detection circuit

“…The physiological results are consistent with anatomical observations, which show gradient expression of mGluR II (stronger in LF neurons) and symmetry between the dorsal and ventral neuropils (Okuda et al 2013;Lu, 2014). Both members of mGluR I (mGluR1 and mGluR5) are detected in chicken NM neurons (Zirpel et al 2000). Our results show that mGluR1 was expressed primarily in cell bodies of NM and NL neurons ( Fig.…”

Translational Concepts of mGluR5 in Synaptic Diseases of the Brain

“…Expression is widespread throughout the mammalian nervous system, including the cerebral cortex (Lopez-Bendito et al, 2002), cerebellar neurons (Berthele et al, 1999), striatal neurons, and the spinal cord (Aronica et al, 2001). Functionally, mGluRs have been implicated as essential mediators of neural development (Zirpel et al, 2000; Di Giorgi Gerevini et al, 2004; Di Giorgi-Gerevini et al, 2005; Jo et al, 2006; Castiglione et al, 2008) and more broadly as important regulators of synaptic strength in the adult brain (Jong et al, 2009; Kumar et al, 2012). …”

Ontogeny of plasma membrane Ca2+ ATPase isoforms in the neural retina of the postnatal rat

“…During development, changes in @Ca 2ϩ # i accompany cell division and differentiation in many neuronal tissues, including the vertebrate retina~Gu et Sugioka et al, 1998;Wong et al, 1998;Zirpel et al, 2000!. Developing retinal cells are subjected to significant @Ca 2ϩ # i loads, arising from ion entry into the cytoplasm via voltage-gated Ca 2ϩ channels, ionotropic glutamate receptor channels, or release from internal stores~Sugioka et al., 1998;Schmid & Guenther, 1999!. Ca 2ϩ fluxes across the plasma membrane, through gap junctions, and between intracellular store compartments and cytoplasm are associated with early synchronized waves of transiently increased @Ca 2ϩ # i~P ozzan et al, 1994!.…”