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Updated: Sep 29, 2025
Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
Published on: July 24, 2019
Activin A regulates the excitability of hippocampal mossy cells
Carla C Schmidt1, Fang Zheng1, Christian Alzheimer1
1Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
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.
Insights
Activin, a TGF-β family member, modulates mossy cell (MC) activity in the hippocampus. This finding is significant for understanding neuropsychiatric disorders like depression and epilepsy.
Area of Science:
- Neuroscience
- Cellular Biology
- Molecular Biology
Background:
- Mossy cells (MCs) in the dentate gyrus (DG) are crucial for hippocampal information processing.
- Dysfunctional MC activity is linked to neuropsychiatric disorders, including epilepsy and major depression.
Purpose of the Study:
- To investigate the neuromodulatory effects of activin on MC activity in the DG.
- To explore the potential role of activin signaling in the pathophysiology and treatment of depression.
Main Methods:
- Whole-cell patch-clamp recordings were performed on MCs in acute hippocampal slices from wild-type and transgenic mice.
- The effects of disrupting activin receptor signaling and applying recombinant activin A were examined.
Main Results:
- Disruption of activin receptor signaling decreased MC firing and altered excitatory/inhibitory inputs.
- Application of activin A increased MC activity and enhanced excitatory synaptic drive.
- Observed changes in MC activity resemble those in rodent models of depression and after antidepressant treatment.
Conclusions:
- Activin exerts a potent neuromodulatory effect on hippocampal mossy cells.
- Activin's influence on MC excitability may contribute to the antidepressant effects of activin signaling in the DG.
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