Additional statistical tests were done with Origin 7 software. Mean periods were compared by two-tailed t tests. Distributions
of periods were compared find more using both Levene’s and Brown-Forsythe’s tests for equal variance. Bicuculline methiodide (Sigma) and SR95531 (gabazine; Tocris) were diluted in water or DMSO. Drugs or vehicle controls were added at less than 0.5% of total volume). We thank B. Carlson, T. Holy, J. Huettner, P. Taghert, C. Zorumski, H. Herzel and members of the Herzog lab for helpful discussions. This work was supported by NIH grants MH63104 (to E.D.H.) and F30NS070376 (to G.M.F.). “
“The discovery of miniature endplate potentials at the neuromuscular junction critically shaped the understanding of neurotransmitter release and synaptic transmission. Since its discovery, spontaneous neurotransmitter release has been described at many synapses in the mammalian CNS but only where ligand-gated ion channels underlie the postsynaptic
response. While a number of G protein-coupled receptors (GPCRs) www.selleckchem.com/products/cx-5461.html are known to mediate inhibitory postsynaptic currents (IPSCs) by activating inwardly rectifying K+ channels (GIRKs), these are thought to result from diffusion of transmitter to extrasynaptic sites (Isaacson et al., 1993; Otis and Mody, 1992). The slow intrinsic kinetics of GPCR signaling and the temporal dispersion of activation resulting from long distance diffusion may obscure GPCR-mediated miniature synaptic events. Electrical stimulation in the midbrain evokes vesicular dopamine release. The lack of structural evidence for axon terminals in the rat substantia Peroxiredoxin 1 nigra pars compacta
(Bayer and Pickel, 1990; Groves and Linder, 1983) led to the theory that dopamine release, in this region, arises from the somatodendritic compartment. Somatodendritic release has been measured using multiple assays (Fortin et al., 2006; Heeringa and Abercrombie, 1995; Mendez et al., 2011), including whole-cell recording of a D2 receptor-dependent IPSC (Beckstead et al., 2004). Spontaneous, or unstimulated, somatodendritic release of dopamine has been detected by amperometry and high-performance liquid chromatography from midbrain dopamine neurons in brain slices (Jaffe et al., 1998) and cultures (Fortin et al., 2006), but there is no evidence that this spontaneous release activates a GIRK-mediated conductance. This study reports spontaneous miniature IPSCs (sIPSCs) in dopamine neurons from mouse substantia nigra pars compacta (SN). The results reveal that spontaneous vesicular dopamine release produced sIPSCs by local D2 receptor activation of GIRK channels that were not dependent on voltage-gated sodium and calcium channels or intracellular calcium stores. Whole-cell voltage-clamp recordings were made from SN dopamine neurons in horizontal midbrain slices from wild-type mice, in the presence of NMDA, AMPA, GABAA, GABAB, and nACh receptor antagonists.