Activin A regulates the excitability of hippocampal mossy cells

Abstract

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.

Tonic activin signaling shapes cellular and synaptic properties of CA1 neurons mainly in dorsal hippocampus

“…Nevertheless, the question remains whether the electrophysiological effects observed in adult dnActRIB neurons are a direct consequence of the lack of activin receptor signaling or rather reflects adaptive changes over time. In a previous study on (glutamatergic) mossy cells in the hilus of the dentate gyrus, 41 we found that administration of recombinant activin A to wild-type neurons produced electrophysiological effects exactly opposite to those observed in dnActRIB neurons. It is therefore plausible to assume that the altered excitability of mutant mossy cells and, by analogy, of the mutant CA1 pyramidal cells examined here, arose directly from disrupted activin receptor signaling.…”

“…Of note, hilar interneurons, which are not supposed to express the transgene, also showed changes in their firing properties when measured in slices from dnActRIB mice. 41 Thus, elimination of endogenous activin signaling in one cell type may entail adaptive changes in other neurons of the hippocampal network.…”

Activin A Reduces GIRK Current to Excite Dentate Gyrus Granule Cells

“…Concerns that the enhanced excitability of GC after EE would affect sparse coding in the dentate gyrus might be dispelled by our observation that a rise in activin A produces also an excitatory effect in mossy cells of the hilus (Schmidt et al, 2022 ). Mossy cells are glutamatergic neurons, which are excited by collaterals of GC axons (mossy fibers).…”