NDLI: PKG and PKA Signaling in LTP at GABAergic Synapses

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PKG and PKA Signaling in LTP at GABAergic Synapses

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PKG and PKA Signaling in LTP at GABAergic Synapses

Content Provider	PubMed Central
Author	Nugent, Fereshteh S. Niehaus, Jason L. Kauer, Julie A.
Abstract	Drugs of abuse usurp the mechanisms underlying synaptic plasticity in areas of the brain, a process that may contribute to the development of addiction (Kauer & Malenka, 2007). We previously reported that GABAergic synapses onto dopaminergic neurons in the ventral tegmental area (VTA) exhibit long term potentiation (LTPGABA) blocked by in vivo exposure to morphine. The presynaptically-maintained LTP requires that retrogradely released nitric oxide (NO) activates a presynaptic cGMP signaling cascade. Previous work reported that inhibitory GABAA receptor synapses in the VTA are also potentiated by cAMP (Bonci & Williams, 1997; Melis et al., 2002). Here we explored the interactions between cGMP-dependent (PKG) and cAMP- dependent (PKA) protein kinases in the regulation of these GABAergic synapses and LTPGABA. Activation of PKG was required for NO-cGMP signaling and was also essential for the induction of synaptically-elicited LTPGABA, but not for its maintenance. Whereas synapses containing GABAA receptors were potentiated by NO-cGMP signaling, synapses containing GABAB receptors on the same cells were not potentiated. Moreover, although the cAMP-PKA system potentiated GABAA synapses, synaptically-induced LTPGABA was independent of PKA activation. Surprisingly, however, raising cGMP levels saturated potentiation of these synapses, precluding further potentiation by cAMP and suggesting a convergent endpoint for both signaling pathways in the regulation of GABAergic release. We further found that persistent GABAergic synaptic modifications observed with in vivo morphine did not involve the presynaptic cAMP-PKA cascade. Taken together, our data suggest a synapse-specific role for NO-cGMP-PKG signaling pathway in opioid-induced plasticity of VTA GABAA synapses.
Related Links	http://dx.doi.org/10.1038/npp.2009.5
Starting Page	1829
File Format	PDF
ISSN	1740634X
e-ISSN	1740634X
Journal	Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Issue Number	7
Volume Number	34
Language	English
Publisher Date	2009-06-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article

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