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

Chad M. Estep, Daniel J. Galtieri, Enrico Zampese, Joshua A. Goldberg, Lars Brichta, Paul Greengard, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageAmerican English
Article numbere0169044
JournalPLoS ONE
Issue number12
StatePublished - Dec 2016

Bibliographical note

Funding Information:
This work was supported by grants from the JPB Foundation (DJS, PG) and the National Institutes of Health (P50NS047085) (DJS). The Fisher Center for Alzheimer’s Research (PG) and the Leon Black Family Foundation (PG).

Publisher Copyright:
© 2016 Estep et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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