Transient, activity dependent inhibition of transmitter release from low threshold afferents mediated by GABA A receptors in spinal cord lamina III/IV

Molecular Pain

Rita Bardoni¹  Amy B. MacDermott²  Chiara Betelli¹ 

[1] Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Campi, 287, Modena, 41125, Italy;Departments of Physiology and Cellular Biophysics, Neuroscience, Columbia University, 630 W. 168th Street, New York 10032, NY, USA

关键词: GABAA;    Dorsal horn;    Presynaptic inhibition;   

Others  :  1229049
DOI  :  10.1186/s12990-015-0067-5

 received in 2015-08-04, accepted in 2015-10-06,  发布年份 2015

【 摘 要 】

Background

Presynaptic GABA _Areceptors (GABA _A Rs) located on central terminals of low threshold afferent fibers are thought to be involved in the processing of touch and possibly in the generation of tactile allodynia in chronic pain. These GABA _A Rs mediate primary afferent depolarization (PAD) and modulate transmitter release. The objective of this study was to expand our understanding of the presynaptic inhibitory action of GABA released onto primary afferent central terminals following afferent stimulation.

Results

We recorded evoked postsynaptic excitatory responses (eEPSCs and eEPSPs) from lamina III/IV neurons in spinal cord slices from juvenile rats (P17–P23, either sex), while stimulating dorsal roots. We investigated time and activity dependent changes in glutamate release from low threshold A fibers and the impact of these changes on excitatory drive. Blockade of GABA _A Rs by gabazine potentiated the second eEPSC during a train of four afferent stimuli in a large subset of synapses. This resulted in a corresponding increase of action potential firing after the second stimulus. The potentiating effect of gabazine was due to inhibition of endogenously activated presynaptic GABA _A Rs, because it was not prevented by the blockade of postsynaptic GABA _A Rs through intracellular perfusion of CsF. Exogenous activation of presynaptic GABA _A Rs by muscimol depressed evoked glutamate release at all synapses and increased paired pulse ratio (PPR).

Conclusions

These observations suggest that afferent driven release of GABA onto low threshold afferent terminals is most effective following the first action potential in a train and serves to suppress the initial strong excitatory drive onto dorsal horn circuitry.

【 授权许可】

   
2015 Betelli et al.

【 图 表 】

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