Synaptic Transmission: Modulation, Plasticity And Effect

综合神经科学实验室(LIN)的研究重点是确定神经调节和可塑性的潜在机制，以及酒精和其他滥用药物对这些神经功能的影响。LIN成立于2001年，实验室主任和同事于2002年2月在突触生理学(SSP)科建立了一个功能实验室。实验室中已经在进行的研究正在研究酒精对NMDA和非NMDA谷氨酸受体功能的影响，以及这些受体介导的突触传递。最近的研究表明，酒精通过促进受体脱敏来抑制AMPA受体的功能。这种受体功能的改变可能是乙醇抑制AMPAR介导的突触传递的基础，而AMPAR介导的突触传递在幼年啮齿动物的海马区尤为明显。在实验室中还对大麻素CB1和烟碱型乙酰胆碱(ACh)受体在背纹突触可塑性中的作用进行了实验研究。这两种受体都在纹状体长时程突触抑制(LTD)的诱导中发挥作用。尼古丁受体刺激多巴胺的释放，这对LTD的诱导至关重要，而由内源性大麻素“逆行信号”激活的CB1受体在LTD的初始阶段将突触后神经元激活与突触前抑制联系起来是至关重要的。由于这些受体是药物滥用的靶标，因此有人推测，这些受体在纹状体突触传递的长期可塑性变化中所起的作用，如LTD，可能在从吸毒到成瘾的转变中发挥重要作用。目前的研究旨在了解将受体激活与可塑性诱导联系起来的细胞内信号，并确定长期抑制传输的机制。LIN扩展的未来计划包括形成行为科学和遗传学(SBSG)和结构生物学(SB)部分，这将使这个实验室小组的工作从单分子到完整的动物。SBSG的设计已经在进行中，计划将分子遗传分析和啮齿动物操纵的新技术与复杂的行为测量相结合。检查的主题可能包括研究酒精敏感和戒断的遗传基础，以及学习和记忆的分子基础。

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.