Activin A regulates the excitability of hippocampal mossy cells.

Carla C Schmidt, Fang Zheng, Christian Alzheimer

Hippocampus 2022 May

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Mossy cells (MCs) in the hilus of the dentate gyrus (DG) receive increasing attention as a major player controlling information processing in the DG network. Furthermore, disturbed MC activity has been implicated in widespread neuropsychiatric disorders such as epilepsy and major depression. Using whole-cell patch-clamp recordings from MCs in acute hippocampal slices from wild type and transgenic mice, we demonstrate that activin, a member of the transforming growth factor-β (TGF-β) family, has a strong neuromodulatory effect on MC activity. Disruption of activin receptor signaling reduced MC firing, dampened their excitatory input and augmented their inhibitory input. By contrast, acute application of recombinant activin A strongly increased MC activity and promoted excitatory synaptic drive. Notably, similar changes of MC activity have been observed in a rodent model of depression and after antidepressant drug therapy, respectively. Given that a rise in activin signaling particularly in the DG has been proposed as a mechanism of antidepressant action, our data suggest that the effect of activin on MC excitability might make a considerable contribution in this regard. © 2022 The Authors. Hippocampus published by Wiley Periodicals LLC.

Citation

Carla C Schmidt, Fang Zheng, Christian Alzheimer. Activin A regulates the excitability of hippocampal mossy cells. Hippocampus. 2022 May;32(5):401-410