BASAL GANGLIA ANATOMY AND PHYSIOLOGY--MECHANISMS OF ACTION OF DRUGS OF ABUSE

MBRS本科生将参加一项正在进行的研究 在科学家导师的指导下。这些对啮齿类动物的研究 将使用电生理学、神经药理学和解剖学 揭示兴奋性药物在尾状核中作用的方法 原子核这个核团和它从黑质输入的多巴胺能 是兴奋剂药物作用的主要场所，包括 安非他明和可卡因。此外，这一主要的综合领域， 基底神经节是亨廷顿病病理学的重要部位， 帕金森氏症。除了阐明滥用药物的作用外， 这项研究将揭示神经元处理的基本方面， 尾状核及其相关的传入系统。 最近的证据表明，突触前的相互作用发生在 黑质纹状体多巴胺能和纹状体多巴胺能之间的尾状核 皮质纹状体传入神经这些相互作用似乎是由 位于传入末梢的自体和异体受体的激活 神经递质从附近的突触释放。这些 突触前的相互作用可能是一个重要的位点的行动， 兴奋剂学生将有机会参加 采用末端轴突测量的电生理研究 电兴奋性来研究这些相互作用。细胞外 记录和终端兴奋性技术也将用于 检查可能的变化，在这两个射击性能的 黑质多巴胺能神经元及其自身受体的变化 尾状核内这些神经元末梢的反馈调节 与大鼠行为敏感化有关的核团 安非他明 我们以前观察到，产前服用可卡因会产生 大鼠尾状核的显著变化。学生将 参与使用相关光和电子的结构研究 基底神经节和相关区域的显微镜检查。 这些 实验将使用免疫细胞化学技术，图像分析， 计算机辅助三维重建，以进一步阐明 这些接触可卡因的动物大脑中所引起的变化。 解剖学研究也提出了准确的特点， 多巴胺能突触的密度，它们的突触后部位，以及 这些突触后部位和其他传入神经之间的关系， 尾状神经元

MBRS undergraduate students will participate in an on-going research program under the guidance of scientist-mentors. These studies on rodents will use electrophysiological, neuropharmacological, and anatomical approaches to reveal the actions of stimulant drugs in the caudate nucleus. This nucleus and its dopaminergic input from the substantia nigra are prominent sites for the action of stimulant drugs, including amphetamine and cocaine. In addition, this major integrative area of the basal ganglia is a significant locus for the pathology of Huntington's and Parkinson's disease. As well as elucidating the action of drugs of abuse, this research will reveal fundamental aspects of neuronal processing in the caudate nucleus and its associated afferent systems. Recent evidence suggests that presynaptic interactions occur in the caudate between dopaminergic nigrostriatal and glutamatergic corticostriatal afferents. These interactions appear to result from the activation of auto- and heteroreceptors located in afferent terminal regions by neurotransmitter released from nearby synapses. These presynaptic interactions may be an important locus for the action of stimulant drugs. Students will have the opportunity to participate in electrophysiological studies employing the measurement of terminal axon electrical excitability to investigate these interactions. Extracellular recording and the terminal excitability technique will also be used to examine possible alterations in both the firing properties of the dopaminergic neurons of the substantia nigra and changes in autoreceptor feedback regulation of the terminals of these neurons within the caudate nucleus related to the behavioral sensitization of the rats to amphetamine. We have previously observed that prenatal cocaine administration produces significant alterations in the rat caudate nucleus. Students will participate in structural studies employing correlated light and electron microscopic examination of basal ganglia and related regions. These experiments will use immunocytochemical techniques, image analysis, and computer assisted three-dimensional reconstruction to further elucidate the changes induced in the brains of these cocaine exposed animals. Anatomical studies are also proposed to accurately characterize the density of dopaminergic synapses, their postsynaptic sites, and the relation between these post-synaptic sites and those of other afferents to caudate neurons.