Glutamatergic Synapses on Hippocampal Interneurons

描述(申请人提供)：兴奋性突触传递为正常的中枢神经系统功能提供基础，兴奋性神经传递的异常导致广泛的神经和精神障碍，如癫痫、精神分裂症和缺血。在体外脑片制备中，对CA3和CA1锥体神经元间树突棘突触的兴奋性突触传递和突触可塑性的研究已经取得了相当大的进展。在这个应用中，我们建议使用电生理记录来检测由相同的传入从CA3锥体细胞到不同的靶群-GABA能中间神经元的兴奋性突触。这些突触与其邻近锥体细胞上的突触具有明显不同的特性。中间神经元几乎没有棘突，所以兴奋性突触几乎只在树突上发现。据报道，中间神经元上的突触也缺乏AMPAR亚单位GluR2。此外，当高频刺激传递给CA3传入时，它们在锥体细胞上产生的突触经历LTP；相反，我们早期的工作表明，对CA3传入的相同高频刺激在突触到中间神经元上触发LTD。相同的突触前传入使这两个靶点上具有不同属性的突触提供了一个独特的机会来比较成熟脑组织中定义和理解的系统中的突触功能、可塑性和调制。这项工作将提供对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的洞察。

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.