LTPGABA in the VTA and its Modulation by Opioids

[unreadable] DESCRIPTION (provided by applicant): My primary area of interest is in the ventral tegmental area (VTA). This brain area consists of a heterogeneous population of neurons, plays a role in endogenous reward and is affected by many drugs of abuse. My colleague and I have found a novel long-term potentiation (LTP) of GABAergic synapses onto VTA dopaminergic neurons which can be altered by opioids in vitro. My project focuses on the characterization of this inhibitory LTP, and its underlying mechanisms. Additionally, I am interested in defining the molecular mechanisms by which opioids modify the excitability of the VTA neurons through the alterations of GABAergic transmission; and plasticity in the VTA. All experiments will be conducted in midbrain slices of rats using visualized patch clamp recording.Aim 1:To characterize the cellular postsynaptic mechanisms underlying the induction of LTPGABA. Aim 2:To determine the retrograde signal that travels from the postsynaptic initiating neuron to direct the presynaptic terminal to release more GABA during LTP.Aim 3: To explore the effects of opioids on this LTPGABA in vivo. Considering the enormous burden of drug addiction on society, the focus of this research is highly important. Studies such as this will provide a better understanding of how drugs of abuse modulate brain circuitry in a way causing an addict to manifest long-term unwanted behavioral changes. This study could also provide the potential targets for anti-addiction drugs. [unreadable] [unreadable] [unreadable]