Glutamatergic Synapses on Hippocampal Interneurons

海马中间神经元上的谷氨酸突触

• 批准号: 7472500
• 负责人: Julie A. Kauer
• 金额: $ 22.84万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472500
• 关键词: Address; Adenosine; Agonist; Arachidonic Acids; Cells; Chromosome Pairing; Data; Dendritic Spines; Endocannabinoids; Epilepsy; Excitatory Synapse; Exhibits; Fiber; Frequencies; Glutamates; Goals; Hippocampus (Brain); In Vitro; Interneurons; Ischemia; Long-Term Depression; Long-Term Potentiation; Mediating; Mental disorders; Neurologic; Neurons; Nitric Oxide; Permeability; Population; Preparation; Probability; Process; Property; Proteins; Pyramidal Cells; Range; Regulation; Reporting; Research Personnel; Schizophrenia; Signal Pathway; Signal Transduction; Signaling Molecule; Slice; Source; Synapses; Synaptic Transmission; Synaptic plasticity; System; Target Populations; Testing; Vertebral column; Work; base; brain tissue; cannabinoid receptor; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; inhibitor/antagonist; insight; neurotransmission; presynaptic; prevent; research study; response; synaptic function; transmission process

DESCRIPTION (provided by applicant): Excitatory synaptic transmission provides the basis of normal CNS function, and abnormalities of excitatory neurotransmission contribute to neurological and psychiatric disorders as wide-ranging as epilepsy, schizophrenia, and ischemia. Considerable progress has been made in understanding the processes that underlie normal excitatory synaptic transmission and synaptic plasticity at dendritic spine synapses between CA3 and CA1 pyramidal hippocampal neurons in the in vitro slice preparation. In this application, we propose to use electrophysiological recording to examine excitatory synapses made by the same afferents from CA3 pyramidal cells onto a different target population, GABAergic interneurons. These synapses have markedly different properties from those on their pyramidal cell neighbors. The interneurons are almost free of spines, so excitatory synapses are found nearly exclusively on dendritic shafts. Synapses on interneurons also are reported to lack the AMPAR subunit, GluR2. Furthermore, when high-frequency stimulation is delivered to CA3 afferents, synapses they make upon pyramidal cells undergo LTP; in contrast, our earlier work demonstrates that the same high-frequency stimulation to CA3 afferents triggers LTD at synapses onto interneurons. The fact that the same presynaptic afferents make synapses with distinct properties onto these two targets affords a unique opportunity to compare synaptic function, plasticity, and modulation in a defined and well-understood system in mature brain tissue. This work will provide insight into the proteins and signaling molecules required for regulation of normal synaptic transmission and plasticity at CNS excitatory synapses.

描述（由申请人提供）：兴奋性突触传递提供了正常CNS功能的基础，兴奋性神经传递异常导致神经和精神疾病，如癫痫、精神分裂症和缺血。在理解正常兴奋性突触传递和突触可塑性的基础上，在体外切片制备的CA 3和CA 1锥体海马神经元之间的树突棘突触的过程中，已经取得了相当大的进展。在这个应用程序中，我们建议使用电生理记录检查兴奋性突触由相同的传入从CA 3锥体细胞到不同的目标群体，GABA能中间神经元。这些突触与它们的锥体细胞邻居具有明显不同的特性。中间神经元几乎没有刺，所以兴奋性突触几乎只在树突轴上发现。据报道，中间神经元上的突触也缺乏AMPAR亚基GluR 2。此外，当高频刺激被传递到CA 3传入，他们在锥体细胞上的突触经历LTP;相反，我们早期的工作表明，同样的高频刺激CA 3传入触发LTD在突触到中间神经元。相同的突触前传入神经在这两个目标上产生具有不同特性的突触，这一事实提供了一个独特的机会来比较成熟脑组织中定义且充分理解的系统中的突触功能、可塑性和调节。这项工作将深入了解调节正常突触传递和中枢神经系统兴奋性突触可塑性所需的蛋白质和信号分子。