Abstract
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 GABAA and GABAB receptors. Although activation of GABAA receptors inhibits spike generation, the consequences of GABAB 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 GABAB receptors hyperpolarized SNc DA neurons, as previously described. However, transient stimulation of GABAB 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 GABAA and GABAB receptors could promote a pause-burst pattern of spiking.
Highlights
substantia nigra pars compacta (SNc) DA neurons play an important role in goal directed movement [1,2,3] and reward-based learning [4,5,6,7]
Our studies have identified a novel mechanism of GABAB receptor modulation of SNc dopaminergic neuron activity
While confirming that GABAB receptor signaling can activate Kir3 K+ channels and suppress spiking when stimulation is sustained, our results show that transient activation of GABAB receptors has a very different effect on ongoing pacemaking
Summary
SNc DA neurons play an important role in goal directed movement [1,2,3] and reward-based learning [4,5,6,7]. As a consequence, their electrophysiological properties have been intensively studied [8,9,10,11,12].
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