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Excitatory actions of GABA in developing chick vestibular afferents: effects on resting electrical activity
Celso Cortes1, Fabian Galindo, Salvador Galicia
1Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Av. 13 Sur 2702 Colonia Volcanes CP, 72410, Puebla, Pue., México.
Insights
Gamma-aminobutyric acid (GABA) enhances vestibular afferent activity during chicken development. This excitatory effect of GABA diminishes with age, suggesting a role in regulating spontaneous activity and glutamate release.
Area of Science:
- Neuroscience
- Developmental Biology
- Auditory and Vestibular Systems
Background:
- Vestibular afferents are crucial for balance and spatial orientation.
- The role of neurotransmitters like GABA in vestibular development is not fully understood.
- Understanding developmental changes in neurotransmission is key to deciphering sensory system maturation.
Purpose of the Study:
- To investigate the developmental effects of gamma-aminobutyric acid (GABA) on vestibular afferent activity.
- To characterize the role of GABAergic signaling in the inner ear during embryonic and early postnatal development.
- To elucidate the mechanisms underlying GABA's influence on vestibular afferent excitability.
Main Methods:
- Isolated inner ear preparations from embryonic (E15-E21) and postnatal (P5) chickens.
- Application of GABA and muscimol to record multiunit activity of vestibular afferents.
- Use of GABAA receptor antagonists (bicuculline, picrotoxin) and chloride channel blockers (9-AC).
- Co-application with glutamatergic antagonists (CNQX, MCPG, 7ClKyn) to assess presynaptic interactions.
Main Results:
- GABA and muscimol increased the basal discharge frequency of vestibular afferents in a dose-dependent manner.
- The excitatory effect of GABA was strongest in early embryonic stages (E15-E17) and decreased significantly by later embryonic (E21) and postnatal (P5) stages.
- GABAA receptor antagonists and chloride channel blockers reduced the excitatory effect of GABA, indicating a GABAA receptor-mediated mechanism.
- Glutamatergic antagonists also reduced basal discharge and GABA's effect, suggesting presynaptic involvement.
Conclusions:
- GABA exerts an excitatory influence on vestibular afferent resting activity during development, likely mediated by GABAA receptors.
- This excitatory role diminishes with developmental progression, possibly due to changes in chloride ion gradients.
- GABA acts presynaptically, potentially facilitating spontaneous activity and modulating glutamate release, but is not the primary neurotransmitter in these synapses.
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.
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