@article {6346,
	title = {IP3 receptor sensitization during in vivo amphetamine experience enhances NMDA receptor plasticity in dopamine neurons of the ventral tegmental area.},
	journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience},
	volume = {30},
	year = {2010},
	month = {2010 May 12},
	pages = {6689-99},
	abstract = {<p>Synaptic plasticity in the mesolimbic dopamine (DA) system is critically involved in reward-based conditioning and the development of drug addiction. Ca2+ signals triggered by postsynaptic action potentials (APs) drive the induction of synaptic plasticity in the CNS. However, it is not clear how AP-evoked Ca2+ signals and the resulting synaptic plasticity are altered during in vivo exposure to drugs of abuse. We have recently described long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated transmission onto DA neurons that is induced in a manner dependent on bursts of APs. LTP induction requires amplification of burst-evoked Ca2+ signals by preceding activation of metabotropic glutamate receptors (mGluRs) generating inositol 1,4,5-trisphosphate (IP3). In this study, using brain slices prepared from male rats, we show that repeated in vivo exposure to the psychostimulant amphetamine (5 mg/kg, i.p., 3-7 d) upregulates mGluR-dependent facilitation of burst-evoked Ca2+ signals in DA neurons of the ventral tegmental area (VTA). Protein kinase A (PKA)-induced sensitization of IP3 receptors mediates this upregulation of mGluR action. As a consequence, NMDAR-mediated transmission becomes more susceptible to LTP induction after repeated amphetamine exposure. We have also found that the magnitude of amphetamine-conditioned place preference (CPP) in behaving rats correlates with the magnitude of mGluR-dependent Ca2+ signal facilitation measured in VTA slices prepared from these rats. Furthermore, the development of amphetamine CPP is significantly attenuated by intra-VTA infusion of the PKA inhibitor H89. We propose that enhancement of mGluR-dependent NMDAR plasticity in the VTA may promote the learning of environmental stimuli repeatedly associated with amphetamine experience.</p>
},
	keywords = {4, 5-Trisphosphate Receptors, Amphetamine, Animals, Calcium, Central Nervous System Stimulants, Classical, Conditioning, Cyclic AMP-Dependent Protein Kinases, Dopamine, Inositol 1, Isoquinolines, Long-Term Potentiation, Male, N-Methyl-D-Aspartate, Neurons, Protein Kinase Inhibitors, Rats, Receptors, Space Perception, Sprague-Dawley, Sulfonamides, Synaptic Transmission, Ventral Tegmental Area},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.4453-09.2010},
	author = {Ahn, Kee-Chan and Bernier, Brian E and Harnett, Mark T and Morikawa, Hitoshi}
}
@article {6348,
	title = {Burst-timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons.},
	journal = {Neuron},
	volume = {62},
	year = {2009},
	month = {2009 Jun 25},
	pages = {826-38},
	abstract = {<p>Bursts of spikes triggered by sensory stimuli in midbrain dopamine neurons evoke phasic release of dopamine in target brain areas, driving reward-based reinforcement learning and goal-directed behavior. NMDA-type glutamate receptors (NMDARs) play a critical role in the generation of these bursts. Here we report LTP of NMDAR-mediated excitatory transmission onto dopamine neurons in the substantia nigra. Induction of LTP requires burst-evoked Ca2+ signals amplified by preceding metabotropic neurotransmitter inputs in addition to the activation of NMDARs themselves. PKA activity gates LTP induction by regulating the magnitude of Ca2+ signal amplification. This form of plasticity is associative, input specific, reversible, and depends on the relative timing of synaptic input and postsynaptic bursting in a manner analogous to the timing rule for cue-reward learning paradigms in behaving animals. NMDAR plasticity might thus represent a potential neural substrate for conditioned dopamine neuron burst responses to environmental stimuli acquired during reward-based learning.</p>
},
	keywords = {2-Amino-5-phosphonovalerate, 4, 5-Trisphosphate, Action Potentials, Animals, Biophysics, Calcium, Dopamine, Dose-Response Relationship, Drug, Electric Stimulation, Enzyme Inhibitors, Excitatory Amino Acid Antagonists, Gene Expression Regulation, Inositol 1, Intracellular Signaling Peptides and Proteins, Long-Term Potentiation, Male, Mesencephalon, Methoxyhydroxyphenylglycol, N-Methyl-D-Aspartate, Neural Pathways, Neuronal Plasticity, Neurons, Peptide Fragments, Rats, Receptors, Sprague-Dawley, Time Factors},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2009.05.011},
	author = {Harnett, Mark T and Bernier, Brian E and Ahn, Kee-Chan and Morikawa, Hitoshi}
}
