title: Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors.
abstract: Among heterogeneous neural cells in the spinal dorsal horn, parvalbumin (PV)-positive neurons are one subtype of GABA (γ-aminobutyric acid)-containing interneurons. Using an optogenetic approach, we expressed blue light-sensitive cation channel channelrhodopsin-2 (ChR2) via a viral vector on PV neurons in the spinal dorsal horn. Combined with in vitro whole-cell recordings, we activated ChR2 expressed on PV neurons by blue light and recorded GABAA receptor-mediated light-evoked inhibitory postsynaptic currents (L-IPSCs). The L-IPSCs were action potential-dependent and abolished by the GABAA receptor antagonist picrotoxin, indicating a synchronic GABA release from presynaptic terminals. Activation of GABAB receptors (the metabotropic receptors of GABA) on presynaptic terminals by a putative agonist, baclofen, depressed the amplitude of L-IPSCs. This depression was largely occluded by pretreatment with the highly selective Cav2.1 (P/Q-type) Ca(2+) channel blocker ω-agatoxin IVA. N-type Ca(2+) channel blocker ω-conotoxin GVIA showed less effects on either L-IPSCs or baclofen depression. We conclude that optoactivation of PV-ChR2 neurons in the spinal dorsal horn induces GABA release from presynaptic terminals, which is modulated by presynaptic GABAB receptors that are coupled to P/Q-type Ca(2+) channels. Importantly, our studies provide a simple and reliable optogenetic approach to study dorsal horn neural circuits.
authors: School of Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: yangk@ujs.edu.cn.
authors: Kun
authors: K
authors: Yang
authors: School of Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Rui
authors: R
authors: Ma
authors: School of Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Qian
authors: Q
authors: Wang
authors: School of Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Ping
authors: P
authors: Jiang
authors: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China.
authors: Yun-Qing
authors: YQ
authors: Li
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D062308:Optogenetics; D010320:Parvalbumins / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D013376:Substantia Gelatinosa / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; D010320:Parvalbumins; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D005680:gamma-Aminobutyric Acid
keywords: GABA; Optogenetics; Pain; Spinal cord; Whole-cell recordings