Transient activation of GABA_B receptors suppresses SK channel currents in substantia nigra pars compacta dopaminergic neurons

Dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) are richly innervated by GABAergic neurons. The postsynaptic effects of GABA on SNc DA neurons are mediated by a mixture of GABA_A and GABA_B receptors. Although activation of GABA_A receptors inhibits spike generation, the consequences of GABA_B receptor activation are less well characterized. To help fill this gap, perforated patch recordings were made from young adult mouse SNc DA neurons. Sustained stimulation of GABA_B receptors hyperpolarized SNc DA neurons, as previously described. However, transient stimulation of GABA_B receptors by optical uncaging of GABA did not; rather, it reduced the opening of small-conductance, calcium-activated K⁺ (SK) channels and increased the irregularity of spiking. This modulation was attributable to inhibition of adenylyl cyclase and protein kinase A. Thus, because suppression of SK channel activity increases the probability of burst spiking, transient co-activation of GABA_A and GABA_B receptors could promote a pause-burst pattern of spiking.