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. 2020 Sep 23;7(5):ENEURO.0376-19.2020. doi: 10.1523/ENEURO.0376-19.2020

Figure 5.

Figure 5.

GABAARs, rather than GIRKs, mediate N/OFQ effects in VTA neurons. A, Example recording showing that the K+ channel blocker BaCl2 (100 μm) did not prevent a N/OFQ-induced outward current in a VTA neuron. B, Blue violin plots representing the distributions of responses of VTA neurons to 10 nm N/OFQ (blue horizontal line = mean; white circle = median; black rectangle = 25th and 75th percentiles). Gray circles show individual responses (single 100 nm experiment in black). There was no difference detected between the distribution of control observations in p22–p36 from adult animals in the presence of BaCl2 have a similar distribution (one tailed permutation analysis of the means, p = 0.2). C, Recordings in 500 nm TTX, 10 μm DNQX, and 10 μm bicuculline to block synaptic activity, AMPARs, and GABAARs, respectively, showed an almost complete elimination of outward currents in VTA neurons in response to N/OFQ (two-tailed permutation analysis of the means, p = 0.16; one tailed permutation analysis of the SDs, p = 0.03). D, Example recording of GABAAR-mediated iontophoretic responses to GABA (in 30 μm CGP35348 to block GABABRs) showing an augmentation of response amplitude in response to 100 nm N/OFQ. E, Summary of the N/OFQ (100 nm)-induced change in iontophoretic response versus change in Iholding, showing both inward and outward N/OFQ-induced currents are highly correlated with N/OFQ-induced changes in iontophoresis amplitude (t = 3.904; df = 4; p = 0.02). F, Example recording in a SNc neuron showing repeated responses to high-concentration (100 nm) N/OFQ, and blockade of the N/OFQ response by BaCl2. G, Summary data from SNc neurons showing minimal desensitization in control experiments with repeated within cell N/OFQ applications at high concentration. H, Summary data from SNc neurons show that BaCl2 prevents a second response to N/OFQ, indicating that in the SNc, N/OFQ outward currents are mediated by K+ channels; **p < 0.01. I, Recording locations for VTA and SNc recordings where N/OFQ was tested in the presence of BaCl2.