GABA(B) receptors negatively modulate excitatory plasticity at the mossy fiber synapse onto parvalbumin-expressing basket and axo-axonic cells in the dentate gyrus

GABA(B)受体负向调节齿状回苔藓纤维突触与表达小白蛋白的篮状细胞和轴突-轴突细胞之间的兴奋性可塑性

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Abstract

INTRODUCTION: GABA(B) receptors (GABA(B)Rs) 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. METHODS: In this study, we have combined quantitative immunoelectron microscopy and ex vivo whole-cell recordings to investigate the surface expression of GABA(B)Rs and their modulation of synaptic plasticity at mossy fiber (MF) inputs onto parvalbumin-expressing interneurons (PV-INs) in the rat dentate gyrus (DG). RESULTS: Immunoelectron microscopy confirmed the expression of the GABA(B)Rs 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 GABA(B)R agonist baclofen. DISCUSSION/CONCLUSION: Finally, pre-application of SCH-23390, a blocker of Kir3 channels, occluded the inhibitory effect of baclofen on LTP. These results demonstrate that postsynaptic GABA(B)Rs negatively regulate synaptic plasticity at MF synapses onto DG perisomatic-inhibitory PV-INs via Kir3 channels.

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