Cells, synapses, and networks contributing to synchrony in the CNS

 描述(申请人提供)：中枢神经系统中的特定活动模式与与觉醒、注意力和记忆形成相关的各种行为状态相关。然而，参与产生这些活动模式的神经元、突触和网络还没有完全被了解。重要的是要理解行为相关活动的各种机制，因为这些信息可能有助于确定与记忆障碍和注意力缺陷相关的中枢神经系统功能障碍的部位-NIMH的优先事项。这项建议旨在帮助确定有助于海马体中主细胞同步振荡的机制，称为theta节奏(4至12赫兹)，它在注意力和记忆形成中发挥作用。在海马区产生theta节律所必需的网络成分包括来自Broca复合体(MS/DBB)的内侧隔/斜角带(MS/DBB)和内嗅皮质(EC)的投射。MS/DBB GABA能投射神经元通过抑制海马局部抑制性中间神经元的节律性抑制，间接同步抑制海马主神经元胞体，从而参与海马theta节律的产生。然而，MS/DBB GABA能投射神经元如何选择性地影响海马锥体神经元胞体而不是它们的树突，目前还不完全清楚。这一假设认为，一种类型的theta节律的产生(类型2)需要MS/DBB GABA能投射神经元对乙酰胆碱的释放和抑制的协同作用，以节律性地激活优先以锥体细胞体细胞为靶点的中间神经元。我们进一步认为，EC输入有节律性地参与海马区中间神经元亚群的活动，这些亚群参与产生1型乙酰胆碱非依赖性theta节律。我们将在脑片中使用光遗传学和电生理学来检验这些假说。目的1研究MS/DBB GABA能神经元对海马CA1区中间神经元的传入。目标2将确定哪些中间神经元可以被乙酰胆碱和MS/DBB GABA能输入节律性激活。目标3将描述阻止其他中间神经元节律性的机制。目的4研究在不存在和存在胆碱能受体激活的情况下，EC输入对海马CA1区中间神经元特定亚群产生节律性的影响。

 DESCRIPTION (provided by applicant): Specific activity patterns in the central nervous system have been correlated with various behavioral states associated with wakefulness, attention and memory formation. However, the neurons, synapses, and networks that contribute to generating these activity patterns are not completely understood. It is important to comprehend the various mechanisms that contribute to behaviorally relevant activity as this information may help identify sites of CNS dysfunction associated with memory impairment and attention deficit - a priority of the NIMH. This proposal seeks to help identify mechanisms contributing to the synchronous oscillation of principal cells in the hippocampus called the theta rhythm (4 to 12 Hz), which plays a role in attention and memory formation. Network components essential for theta rhythm generation in the hippocampus include projections from the medial septum/diagonal band of Broca complex (MS/DBB) and the entorhinal cortex (EC). MS/DBB GABAergic projection neurons play a role in hippocampal theta rhythm generation by synchronously inhibiting hippocampal principal neuron somata indirectly through the rhythmic inhibition of local hippocampal inhibitory interneurons. However, how the MS/DBB GABAergic projection neurons selectively affect hippocampal pyramidal neuronal somata and not their dendrites is not fully understood. This proposal hypothesizes that one type of theta rhythm generation (type 2) requires the concerted actions of acetylcholine release and inhibition by MS/DBB GABAergic projection neurons to rhythmically activate interneurons that preferentially target pyramidal cell somata. We further propose that EC inputs rhythmically engage subsets of hippocampal interneurons that are involve in generating type 1 acetylcholine-independent theta rhythm. We will test these hypotheses using optogenetics and electrophysiology in brain slices. Aim 1 will characterize the MS/DBB GABAergic input onto hippocampal CA1 interneurons. Aim 2 will determine which interneurons can be rhythmically activated by acetylcholine and MS/DBB GABAergic inputs. Aim 3 will characterize the mechanisms that prevent rhythmicity in other interneurons. Aim 4 will investigate the impact that EC input have on generating rhythmicity in specific subsets of hippocampal CA1 interneurons in the absence and presence of cholinergic receptor activation.