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01-06-2022 | Original Article

GABA_B receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord

Authors: Mingwei Zhao, Caifeng Shao, Jiaxue Dong, Qian Chen, Rui Ma, Ping Jiang, Wei-Ning Zhang, Kun Yang

Published in: Brain Structure and Function | Issue 5/2022

Abstract

The substantia gelatinosa (SG, lamina II of spinal cord gray matter) is pivotal for modulating nociceptive information from the peripheral to the central nervous system. γ-Aminobutyric acid type B receptors (GABA_BRs), the metabotropic GABA receptor subtype, are widely expressed in pre- and postsynaptic structures of the SG. Activation of GABA_BRs by exogenous agonists induces both pre- and postsynaptic inhibition. However, the actions of endogenous GABA via presynaptic GABA_BRs on glutamatergic synapses, and the postsynaptic GABA_BRs interaction with glutamate, remain elusive. In the present study, first, using in vitro whole-cell recordings and taking minimal stimulation strategies, we found that in rat spinal cord glutamatergic synapses, blockade of presynaptic GABA_BRs switched “silent” synapses into active ones and increased the probability of glutamate release onto SG neurons; increasing ambient GABA concentration mimicked GABA_BRs activation on glutamatergic terminals. Next, using holographic photostimulation to uncage glutamate on postsynaptic SG neurons, we found that postsynaptic GABA_BRs modified glutamate-induced postsynaptic potentials. Taken together, our data identify that endogenous GABA heterosynaptically constrains glutamate release via persistently activating presynaptic GABA_BRs; and postsynaptically, GABA_BRs modulate glutamate responses. The results give new clues for endogenous GABA in modulating the nociception circuit of the spinal dorsal horn and shed fresh light on the postsynaptic interaction of glutamate and GABA.

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Title: GABAB receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord
Authors: Mingwei Zhao
Caifeng Shao
Jiaxue Dong
Qian Chen
Rui Ma
Ping Jiang
Wei-Ning Zhang
Kun Yang
Publication date: 01-06-2022
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 5/2022
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-022-02481-2

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GABA_B receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord

Abstract

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Abstract

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