Summary GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc) and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). In vivo morphine treatment resulted in tolerance to the inhibition of RMTg inputs, but not local interneurons or NAc inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.

D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors.DOI: http://dx.doi.org/10.7554/eLife.09358.001

Although the primate insular cortex has been studied extensively, a comprehensive investigation of its neuronal morphology has yet to be completed. To that end, neurons from 20 human subjects (10 males and 10 females; N = 600) were selected from the secondary gyrus brevis, precentral gyrus, and postcentral gyrus of the left insula. The secondary gyrus brevis was generally more complex in terms of dendritic/spine extent than either the precentral or postcentral insular gyri, which is consistent with the posterior-anterior gradient of dendritic complexity observed in other cortical regions. The male insula had longer, spinier dendrites than the female insula, potentially reflecting sex differences in interoception. In comparing the current insular data with regional dendritic data quantified from other Brodmann's areas (BAs), insular total dendritic length (TDL) was less than the TDL of high integration cortices (BA6beta, 10, 11, 39), but greater than the TDL of low integration cortices (BA3-1-2, 4, 22, 44). Insular dendritic spine number was significantly greater than both low and high integration regions. Overall, the insula had spinier, but shorter neurons than did high integration cortices, and thus may represent a specialized type of heteromodal cortex, one that integrates crude multisensory information crucial to interoceptive processes.