In recent years, considerable progress has been achieved in deciphering the cellular and network functions of GABAergic transmission in the intact developing brain. First, in vivo studies in non-mammalian and mammalian species confirmed the long-held assumption that GABA acts as a mainly depolarizing neurotransmitter at early developmental stages. At the same time, GABAergic transmission was shown to spatiotemporally constrain spontaneous cortical activity, whereas firm evidence for GABAergic excitation in vivo is currently missing. Second, there is a growing body of evidence indicating that depolarizing GABA may contribute to the activity-dependent refinement of neural circuits. Third, alterations in GABA actions have been causally linked to developmental brain disorders and identified as potential targets of timed prophylactic interventions. In this article, we review these major recent findings and argue that both depolarizing and inhibitory GABA actions may be crucial for physiological brain maturation.
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http://dx.doi.org/10.1177/1073858417701382 | DOI Listing |
J Neurochem
January 2025
School of Life Science, Nanchang University, Nanchang, China.
Activation of the brain-penetrant beta3-adrenergic receptor (Adrb3) is implicated in the treatment of depressive disorders. Enhancing GABAergic inputs from interneurons onto pyramidal cells of prefrontal cortex (PFC) represents a strategy for antidepressant therapies. Here, we probed the effects of the activation of Adrb3 on GABAergic transmission onto pyramidal neurons in the PFC using in vitro electrophysiology.
View Article and Find Full Text PDFMicroRNA-502-3p (MiR-502-3p), a synapse enriched miRNA is considerably implicated in Alzheimer's disease (AD). Our previous study found the high expression level of miR-502-3p in AD synapses relative to controls. Further, miR-502-3p was found to modulate the GABAergic synapse function via modulating the GABA A receptor subunit α-1 (GABRA1) protein.
View Article and Find Full Text PDFPharmacol Res
January 2025
Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Vienna, Austria. Electronic address:
α6-containing GABA receptors (α6GABARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavior. Activation of α6GABARs enhances the precision of sensory inputs, enables rapid and coordinated movement and adequate responses to the environment, and protects the brain from information overflow.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
The Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Asahikawa, Japan.
The evolution of brain-expressed genes is notably slower than that of genes expressed in other tissues, a phenomenon likely due to high-level functional constraints. One such constraint might be the integration of information by neuron assemblies, enhancing environmental adaptability. This study explores the physiological mechanisms of information integration in neurons through three types of synchronization: chemical, electromagnetic, and quantum.
View Article and Find Full Text PDFNeuropharmacology
January 2025
Developmental Exposure Alcohol Research Center, Behavioral Neuroscience Program, Department of Psychology, Binghamton, NY, 13902-6000, USA. Electronic address:
Alcohol binge drinking has a multitude of effects on CNS function, including changes in inflammatory cytokines such as IL-6 and IL-1β that may contribute to mood fluctuations associated with the intoxication-withdrawal cycle. Widely throughout the brain, including the amygdala, IL-6 mRNA is enhanced during intoxication, whereas IL-1β is initially suppressed during alcohol intoxication, with increased expression seen shortly after ethanol clearance, during acute hangover. Furthermore, induction of neuroimmune genes appears to be muted during adolescence in the amygdala, suggesting a broader functional immaturity of the adolescent neuroimmune system in structures involved in negative affect associated with ethanol exposure.
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