Synaptic activity-induced Ca2+ signaling in avian cochlear nucleus magnocellularis neurons

Neurons of the avian cochlear nucleus magnocellularis (NM) receive glutamatergic inputs from the spiral ganglion cells via the auditory nerve and feedback GABAergic inputs primarily from the superior olivary nucleus. We investigated regulation of Ca2+ signaling in NM neurons with ratiometric Ca2+ imaging in chicken brain slices. Application of exogenous glutamate or GABA increased the intracellular Ca2+ concentration ([Ca2+]i) in NM neurons. Interestingly, GABA-induced Ca2+ responses persisted into neuronal maturation, in both standard and energy substrate enriched artificial cerebrospinal fluid. More importantly, we found that electrical stimulation applied to the glutamatergic and GABAergic afferent fibers innervating the NM was able to elicit transient [Ca2+]i increases in NM neurons, and the amplitude of the Ca2+ responses increased with increasing frequency and duration of the electrical stimulation. Antagonists for ionotropic glutamate receptors significantly blocked these [Ca2+]i increases, whereas blocking GABAA receptors did not affect the Ca2+ responses, suggesting that synaptically released glutamate but not GABA induced the Ca2+ signaling in vitro. Furthermore, activation of GABAA receptors with exogenous agonists inhibited synaptic activity-induced [Ca2+]i increases in NM neurons, suggesting a role of GABAA receptors in the regulation of Ca2+ homeostasis in the avian cochlear nucleus neurons.

► Synaptic glutamate results in [Ca2+]i increases in avian cochlear nucleus neurons.
► Ionotropic glutamate receptors primarily mediate these [Ca2+]i increases.
► GABAA receptors inhibit these [Ca2+]i increases, regulating calcium homeostasis.