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机制以及酒精和其他药物滥用对这些神经功能的影响。该实验室成立于2001年，实验室主任及其同事于2002年2月在突触生理学（SSP）部门建立了一个功能实验室。已经在实验室进行的研究正在检查酒精对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，这在幼龄啮齿动物的海马中尤为突出。在实验室也进行了大麻素CB1和烟碱乙酰胆碱（ACh）受体在背体突触可塑性中的作用的实验。这两种受体都在纹状体长期突触抑制（LTD）的诱导中发挥作用。尼古丁受体刺激多巴胺释放，这对LTD的诱导至关重要，而CB1受体被内源性大麻素“逆行信号”激活，在LTD初始阶段连接突触后神经元激活和突触前抑制至关重要。由于这些受体是药物滥用的靶点，因此有人假设这些受体在纹状体突触传递（如LTD）的长期可塑性变化中所起的作用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连接受体激活和可塑性诱导的细胞内信号，并确定长期抑制传递的机制。LIN未来的扩展计划包括形成行为科学和遗传学（SBSG）和结构生物学（SB）部门，将在这个实验室小组从单个分子到完整动物的工作。SBSG的设计已经在进行中，计划将分子遗传分析和操纵啮齿动物的新技术与复杂的行为测量相结合。要检查的主题可能包括检查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.