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Dorsal-Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion
Valero-Aracama, M.J.; Zheng, F.; Alzheimer, C. Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion. Int. J. Mol. Sci.2023, 24, 13145.
Valero-Aracama, M.J.; Zheng, F.; Alzheimer, C. Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion. Int. J. Mol. Sci. 2023, 24, 13145.
Valero-Aracama, M.J.; Zheng, F.; Alzheimer, C. Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion. Int. J. Mol. Sci.2023, 24, 13145.
Valero-Aracama, M.J.; Zheng, F.; Alzheimer, C. Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion. Int. J. Mol. Sci. 2023, 24, 13145.
Abstract
The functional and neurophysiological distinction between dorsal and ventral hippocampus affects also GABAergic inhibition. In line with his notion, ventral CA1 pyramidal cells displayed a more dynamic and effective response to inhibitory input compared to their dorsal counterparts. We posit that this difference is effected by the dorsal-ventral gradient of activin A, a member of the transforming growth factor-β family, which is increasingly recognized for its modulatory role in brain regions involved in cognitive functions and affective behavior. Lending credence to this hypothesis, we found that in slices from transgenic mice expressing a dominant-negative mutant of activin receptor IB (dnActRIB), inhibitory transmission was enhanced only in CA1 neurons of dorsal hippocampus, where basal activin A level is much higher than in ventral hippocampus. We next asked how a rise in endogenous activin A would affect GABAergic inhibition along the longitudinal axis of the hippocampus. We performed ex vivo recordings from wild type and dnActRIB mice after overnight exposure to an enriched environment (EE), which engenders a robust increase in activing A levels in both dorsal and ventral hippocampi. Compared to control mice from standard cages, the behaviorally induced surge in activin A produced a decline in ventral inhibition, an effect that was absent in slices from dnActRIB mice. Underscoring the essential role of activin in the EE-associated modulation of ventral inhibition, this effect was mimicked by acute application of recombinant activin A in control slices. In summary, both genetic and behavioral manipulations of activin receptor signaling affected the dorsal-ventral difference in synaptic inhibition, suggesting that activin A regulates the strength of GABAergic inhibition in a region-specific fashion.
Biology and Life Sciences, Neuroscience and Neurology
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