Research articleOptoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

- PV interneurons in the spinal dorsal horn can be optogenetically labeled and activated.
- Selective activation of PV neurons induces GABA release.
- Activation of GABAB receptors on PV neuron terminals depresses GABA release.
- Baclofen activity on GABA release is mainly mediated by P/Q type Ca2+ channels.

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) Ca2+ channel blocker ω-agatoxin IVA. N-type Ca2+ 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 Ca2+ channels. Importantly, our studies provide a simple and reliable optogenetic approach to study dorsal horn neural circuits.