JULIE KAUER

..This common response may represent a starting point for dissecting early changes that underlie addiction...

..Here we put this work into the context of other examples of synaptic plasticity at GABAergic synapses...

..Here, we review evidence that TRPV channels in the central nervous system might contribute to many basic neuronal functions including resting membrane potential, neurotransmitter release and synaptic plasticity...

..This review focuses on alterations in cellular and synaptic physiology in the ventral tegmental area (VTA) in response to addictive drugs...

..These neuroadaptations to opioid drugs might contribute to early stages of addiction, and may potentially be exploited therapeutically using drugs targeting GABA(A) receptors...

..However, unlike the case for any previously described form of LTD, activation of cyclic AMP-dependent protein kinase (PKA) is necessary and sufficient to trigger LTD at synapses on VTA dopamine neurons...

..Innovative treatments directly targeting these drug-induced changes in brain reward components and circuits may be efficacious in reducing drug use and relapse...

..We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse...

..Our results support the notion that after psychostimulant exposure, excitatory synapses on NAc neurons alter their response to further psychostimulant for long periods of time...

..Dysregulation of this mechanism could contribute to the impairment in cognitive performance associated with abnormal PFC dopamine receptor activation...

..Reversing or preventing these drug-induced synaptic modifications may prove beneficial in the treatment of one of society's most intractable health problems...

..Field potential recordings may provide a convenient approach to explore the basic electrophysiological properties of VTA neurons and the development of addiction-related processes in this brain region...

..Like other forms of hippocampal synaptic plasticity, TRPV1-mediated LTD may have a role in long-term changes in physiological and pathological circuit behavior during learning and epileptic activity...

..Taken together, our data suggest a synapse-specific role for NO-cGMP-PKG signaling pathway in opioid-induced plasticity of VTA GABA(A) synapses...

..Thus, recycling endosomes supply AMPA receptors for LTP and provide a mechanistic link between synaptic potentiation and membrane remodeling during synapse modification...

..I expect our work to elucidate the cellular mechanisms by which opioid compounds alter the normal function of this brain area essential for normal reward processing. ..

..This work will provide insight into the proteins and signaling molecules required for regulation of normal synaptic transmission and plasticity at CNS excitatory synapses. ..

..I expect our work to elucidate the cellular mechanisms by which opioid compounds alter the normal function of this brain area essential for normal reward processing. ..

..We expect that the proposed studies will confirm our in vitro work, and provide important new leads to use in that work. ..

..We will continue using electrophysiological methods to examine the effects of amphetamine on neurons in the VTA slice preparation. ..

..Here we will explore the novel hypothesis that TRPV1 contributes to hippocampal excitability, and could represent a novel therapeutic target for epileptic seizures. ..