ORIGINAL RESEARCH article
Front. Synaptic Neurosci.
This article is part of the Research TopicThe Interplay Between GABA and Glutamate in Systems Physiology and PathophysiologyView all 5 articles
GABAB receptors negatively modulate excitatory plasticity at the mossy fiber synapses onto parvalbumin-expressing Basket and Axo-axonic cells in the Dentate Gyrus
Provisionally accepted
- 1NeuroCure Cluster, Institute of Integrative Neuroanatomy, Charité Medical University of Berlin, Berlin, Germany
- 2The University of Edinburgh Centre for Discovery Brain Sciences, Edinburgh, United Kingdom
- 3Albert-Ludwigs-Universitat Freiburg Physiologische Institute I und II, Freiburg, Germany
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GABAB receptors (GABABRs) are important modulators of neuronal excitability, synaptic transmission and plasticity in principal cells (PCs). While at the cellular level they can inhibit synaptic transmission directly, at the network level, due to a net disinhibitory effect, they promote plasticity in PCs. However, their effect on plasticity in GABAergic interneurons (INs) is less well-understood. In this study, we have combined quantitative immunoelectron microscopy and ex vivo whole-cell recordings to investigate the surface expression of GABABRs and their modulation of synaptic plasticity at mossy fiber (MF) inputs onto parvalbumin-expressing interneurons (PV-INs) in the rat dentate gyrus (DG). Immunoelectron microscopy confirmed the expression of the GABABRs and their effector channel Kir3.1 on PV-IN dendritic shafts. Theta-burst extracellular stimulation of MFs resulted in robust long-term potentiation (LTP) in basket cells (BCs) and axo-axonic cells (AACs), the two main types of DG PV-INs. LTP in both types was strongly reduced, but not abolished, by the GABABR agonist baclofen. Finally, pre-application of SCH-23390, a blocker of Kir3 channels, occluded the inhibitory effect of baclofen on LTP. These results demonstrate that postsynaptic GABABRs negatively regulate synaptic plasticity at MF synapses onto DG perisomatic-inhibitory PV-INs via Kir3 channels.
Keywords: GABAB receptors, excitatory plasticity, mossy fiber synapses, parvalbumin-expressing Basket, axo-axonic cells, Dentate Gyrus
Received: 30 Jun 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Pinto McKay Loureiro, Booker, Kulik and Vida. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Imre Vida, imre.vida@charite.de
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