Glutamatergic inhibition of voltage-operated calcium channels in the avian cochlear nucleus

Abstract

The auditory nerve serves as the only excitatory input to neurons in the avian cochlear nucleus, nucleus magnocellularis (NM). NM neurons in immature animals are dependent upon auditory nerve signals; when deprived of them, many NM neurons die, and the rest atrophy. Auditory nerve terminals release glutamate, which can stimulate second messenger systems by activating a metabotropic glutamate receptor (mGluR). Therefore, it is possible that the effecters of mGluRstimulated signal transduction systems are needed for NM neuronal survival. This study shows that mGluR activation in NM neurons attenuates voltage-dependent changes in [Ca2+],. Voltage-dependent Ca2+ influx was also attenuated by increasing CAMP with forskolin, VIP, or 8-bromo-CAMP, indicating that mGluR activation may stimulate adenylate cyclase. The main results may be summarized as follows. NM neurons possess high voltage-activated Ca*+ channels that were modulated by quisqualate, glutamate, and (?)transACPD, in that order of potency. Glutamatergic inhibition of Ca2+ influx was not blocked by L-AP3 or L-AP4, which antagonize the actions of mGluRs in other neural systems; it was blocked by serine-Ophosphate. Finally, the attenuation of voltage-dependent Ca*+ influx was duplicated by CAMP accumulators. Since NM neurons have high rates of spontaneous activity and higher rates of driven activity, the expression of this mGluR turns out to be very valuable: without it, [Ca2+], could reach lethal concentrations. These results provide an important clue as to the identity of an intracellular signal that may play an important role in NM neuronal survival.

Glutamate Inhibits GABA Excitatory Activity in Developing Neurons

“…When compared with a group (n ϭ 32) receiving GABA plus kainate (5 M), the group treated with GABA plus CCG showed a much greater decrease (t test; p Ͻ 0.0001). Thus, activation of a CCGsensitive mGluR inhibited GABA-mediated C a 2ϩ rises, probably at a postsynaptic site, as described for mGluR activation in other systems (Lachica et al, 1995).…”

Initial Phase of Neuropathic Pain within a Few Hours after Nerve Injury in Mice

“…The spontaneous periodic activity in the spiral ganglion neurons is required for the refinement and maintenance of tonotopic maps in the auditory system (Tritsch et al, 2007). The absence of afferent activities results in sustained elevation of the intracellular calcium concentration, which causes cell death in some of the cochlear nucleus neurons (Lachica et al, 1995;Zirpel et al, 1998). Basal firing in peripheral sensory nerves is also important in the maintenance of sensory functions of adult animals.…”

Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns

“…Accumulating evidence indicates that this spontaneous activity plays a critical role in neuronal survival (Lachica et al 1995;Zirpel and Rubel 1996) and in the normal physiological and anatomical development of central auditory connections (Gabriele et al 2000;Kitzes et al 1995;Russell and Moore 1995;reviewed in Sanes and Friauf 2000). Spontaneous activity in the immature auditory system is rhythmic and oscillatory, consisting of bursts of activity that are separated by periods of low-frequency events (Jones and Perez 2001;Kotak and Sanes 1995;Lippe 1994), a pattern that is reminiscent of the activity patterns in other developing systems (reviewed in Zhang et al 2000).…”

“…In this nucleus, glutamate released from 8th nerve terminals activates postsynaptic metabotropic glutamate receptors (mGluRs) that mobilize intracellular calcium. This activates protein kinases A and C, which in turn inhibit voltagegated calcium channels, thereby preventing accumulation of toxic levels of [Ca 2ϩ ] i (Lachica et al 1995;Zirpel and Rubel 1996;Zirpel et al 1998).…”

“…In this nucleus, glutamate released from 8th nerve terminals activates postsynaptic metabotropic glutamate receptors (mGluRs) that mobilize intracellular calcium. This activates protein kinases A and C, which in turn inhibit voltagegated calcium channels, thereby preventing accumulation of toxic levels of [Ca 2ϩ ] i (Lachica et al 1995;Zirpel and Rubel 1996;Zirpel et al 1998).Recent evidence has indicated that calcium-dependent mechanisms are also crucial for the survival and maturation of neurons in the LSO (Lohmann et al 1998), but the mechanisms by which synaptic activity increases [Ca 2ϩ ] i in the LSO are poorly understood. We have previously shown that glycinergic/GABAergic synapses in the MNTB-LSO pathway increase [Ca 2ϩ ] i during the period when these synapses are depolarizing and are functionally eliminated (Kandler and Friauf 1995;Kim and Kandler 2003;Kullmann et al 2002).…”