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G protein-coupled receptors (GPCRs) affect many physiological processes by modulating both intrinsic membrane conductances and synaptic transmission. This study describes spontaneous miniature inhibitory postsynaptic currents mediated by vesicular dopamine release acting locally on metabotropic D 2 receptors leading to the activation of a G protein-coupled inwardly rectifying potassium conductance...
Cellular responsiveness to many neuromodulators is controlled by endocytosis of the transmembrane receptors that transduce their effects. Endocytic membrane trafficking of particular neuromodulator receptors exhibits remarkable diversity and specificity, determined largely by molecular sorting operations that guide receptors at trafficking branchpoints after endocytosis. In this Review, we discuss...
By distinguishing groups of dopamine neurons that differ in their projection patterns and intrinsic properties, Lammel and colleagues report in this issue of Neuron that mesocorticolimbic dopamine neurons of the ventral tegmental area (VTA) form a distinct subclass of dopamine cells.
Changes in cytosolic calcium are crucial for numerous processes including neuronal plasticity. This study investigates the regulation of cytosolic calcium by corticotropin-releasing factor (CRF) in midbrain dopamine neurons. The results demonstrate that CRF stimulates the release of intracellular calcium from stores through activation of adenylyl cyclase and PKA. Imaging and photolysis experiments...
Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sensitive,...
Control of trafficking of g protein-linked receptors is thought to be an important regulatory mechanism for receptor signaling. Finn and Whistler test the hypothesis that agonist-induced trafficking of opioid receptors regulates the development of tolerance and dependence. The results show that measures of tolerance and withdrawal to morphine are decreased under conditions where receptors are trafficked...
The mesolimbic system is known to play a role in self-administration of opioids and psychostimulants. Although morphine and cocaine act by separate cellular mechanisms initially, the present study describes a common change in synaptic regulation of dopamine cells in the ventral tegmental area 1 week after termination of chronic treatment with either drug. Normally, D1 receptor activation augmented...
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