Synaptic Transmission: Modulation, Plasticity And Effect

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The focus of research in the Laboratory of Integrative Neuroscience (LIN) is the determination of mechanisms underlying neuromodulation and plasticity and the effects of alcohol and other drugs of abuse on these neural functions. The LIN was established in 2001 and the Laboratory Chief and coworkers established a functional laboratory in the Section on Synaptic Physiology (SSP) in February 2002. Studies already underway in the laboratory are examining alcohol effects on NMDA and non-NMDA glutamate receptor function and synaptic transmission mediated by these receptors. Recent findings indicate that alcohol inhibits AMPA receptor function by promoting receptor desensitization. This alteration in receptor function may underlie ethanol inihibition of AMPAR-mediated synaptic transmission which is particularly prominent in the hippocampus of young rodents. Experiments in the laboratory are also conducted on the role of cannabinoid CB1 and nicotinic acetylcholine (ACh) receptors in synaptic plasticity in dorsal striaum. Both receptors play a role in the induction of striatal long-term synaptic depression (LTD). Nicotinic receptors stimulate dopamine release that is crucial for LTD induction, while CB1 receptors activated by an endocannabinoid "retrograde signal" are crucial in linking postsynaptic neuronal activation to presynaptic inhibition during the initial phases of LTD. Because these receptors are targets for drugs of abuse, it has been hypothesized that the role of these receptors in long-lasting plastic changes in striatal synaptic transmission such as LTD could play important roles in transition from drug-taking to addiction. Current studies are aimed at understanding the intracellular signals that link receptor activation to induction of plasticity, and determining the mechanisms involved in long-lasting depression of transmission. Future plans for LIN expansion include the formation of Sections on Behavioral Science and Genetics (SBSG) and Structural Biology (SB) that will take work in this laboratory group from single molecules up to the intact animal. Design of the SBSG is already underway, and plans are to combine new techniques for molecular genetic analysis and manipulation of rodents with sophisticated behavioral measurements. Topics to be examined are likely to include examinination of the genetic basis of alcohol sensitivity and withdrawal, and the molecular basis of learning and memory.