Excitatory actions of GABA in developing chick vestibular afferents: Effects on resting electrical activity

Abstract

The aim of this study was to characterize the effect of γ-aminobutyric acid (GABA) in the resting multiunit activity of the vestibular afferents during development using the isolated inner ear of embryonic and postnatal chickens (E15-E21 and P5). GABA (10(-3) to 10(-5) M; n = 133) and muscimol (10(-3) M) elicited an increase in the frequency of the basal discharge of the vestibular afferents. We found that GABA action was dose-dependent and inversely related to animal age. Thus, the largest effect was observed in embryonic ages such as E15 and E17 and decreases in E21 and P5. The GABAA receptor antagonists, bicuculline (10(-5) M; n = 10) and picrotoxin (10(-4) M; n = 10), significantly decreased the excitatory action of GABA and muscimol (10(-3) M). Additionally, CNQX 10(-6) M, MCPG 10(-5) M and 7ClKyn 10(-5) M (n = 5) were co-applied by bath substitution (n = 5). Both the basal discharge and the GABA action significantly decreased in these experimental conditions. The chloride channel blocker 9-AC 0.5 mM produced an important reduction in the effect of GABA 10(-3) (n = 5) and 10(-4) M (n = 5). Thus, our results suggest an excitatory role of GABA in the resting activity of the vestibular afferents that can be explained by changes in the gradient of concentration of Cl(-) during development. We show for the first time that the magnitude of this GABA effect decreases at later stages of embryonic and early postnatal development. Taking into account the results with glutamatergic antagonists, we conclude that GABA has a presynaptic action but is not the neurotransmitter in the vestibular afferent synapses, although it could act as a facilitator of the spontaneous activity and may regulate glutamate release.

Novel functions of GABA signaling in adult neurogenesis

“…GABA excitatory role during the first postnatal week was assessed in a recent study with chick vestibular afferents (Cortes et al, 2013). The inner ear of chicken was isolated and tested with GABA antagonists and agonists.…”

“…This study confirmed that GABA’s excitatory property decreases gradually along neuronal maturation. Since NMDARs had already been characterized as the main vestibular afferent neurotransmitter for many species, the study evaluated the correlations between the glutamatergic and GABAergic inputs, and found that GABA is involved in the activation of NMDARs and regulation of glutamate release (Cortes et al, 2013). …”

Physiological Differences in the Follicular, Luteal, and Menstrual Phases in Healthy Women Determined by Electrovestibulography: Depression, Anxiety, or Other Associations?

“…Figure 8d shows the control and MDD IH33 responses from [12] with the more “depressive like” menses response overlaid. Cortes et al [25] suggested that GABA could act as a facilitator in the spontaneous discharge of the vestibular afferents by altering the intracellular Ca++ concentration. In support, diazepam (a GABA-A receptor agonist) has been observed to significantly reduce spontaneous neuronal activity in the medial VN [11].…”

Neuropharmacological Targets for Drug Action in Vestibular Sensory Pathways

“…GABA-like immunoreactivity in efferent endings of the mammal was reported in the squirrel monkey but not rat or guinea pig and in the bird GABA labeling was reported for the pigeon with weak labeling in the chicken [ 25 ]. Electrophysiological studies also showed that the application of GABA agonists and antagonists had no direct effect on the vestibular afferents [ 26 ]. These investigators plausibly argued that GABA is not the neurotransmitter in the afferent synapse, but may be a facilitator of glutamate release.…”