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

有助于中枢神经系统同步的细胞、突触和网络

基本信息

批准号：
9106990
负责人：
ADAM RORY MCQUISTON
金额：
$ 38.13万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-11 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106990
关键词：
Acetylcholine Action Potentials Acute Address Affect Atropine Attention Axon Behavioral Brain Cells Cholinergic Receptors Code Complex Coupled Dendrites Diagonal Band of Broca Electrophysiology (science)Exploratory Behavior Fire - disasters Functional disorder Generations Goals Hippocampus (Brain)Injection of therapeutic agent Interneuron function Interneurons Kinetics Learning Light Medial Memory Memory impairment Mental disorders Mus Muscarinic Acetylcholine Receptor National Institute of Mental Health Neuraxis Neurons Pathway interactions Pattern Periodicity Play Probability Process Property Proteins Pyramidal Cells REM Sleep Receptor Activation Reporter Resistance Rodent Role Site Slice Synapses Testing Theta Rhythm Time Viral Wakefulness base cholinergic entorhinal cortex hippocampal pyramidal neuron in vivo neuronal cell body optogenetics postsynaptic presynaptic prevent public health relevance receptor response selective expression

项目摘要

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.

描述（由申请人提供）：中枢神经系统中的特定活动模式与觉醒、注意力和记忆形成相关的各种行为状态相关，然而，有助于产生这些活动模式的神经元、突触和网络并不完全相关。了解导致行为相关活动的各种机制非常重要，因为这些信息可能有助于识别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，这是 NIMH 的一个优先事项，旨在帮助识别导致行为相关活动的机制。同步海马体中主要细胞的振荡称为 θ 节律（4 至 12 Hz），它在注意力和记忆形成中发挥作用，对于海马体中 θ 节律的产生至关重要的网络组件包括来自布罗卡复合体内侧隔膜/对角带的投射。（MS/DBB）和内嗅皮层（EC）GABA能投射神经元通过同步抑制在海马θ节律的产生中发挥作用。海马主神经元体体通过局部海马抑制性中间神经元的节律性抑制间接实现。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体体而不是其树突，这一提议促进了一种类型的θ节律的产生。（类型 2）需要 MS/DBB GABA 能投射神经元释放乙酰胆碱并抑制其协同作用，以有节奏地激活中间神经元我们进一步提出，EC 输入有节奏地参与产生 1 型乙酰胆碱依赖性 θ 节律的海马中间神经元亚群，我们将在脑切片中使用光遗传学和电生理学来测试这些假设。 MS/DBB GABAergic 输入到海马 CA1 中间神经元，目标 2 将确定哪些中间神经元可以被有节奏地激活。目标 3 将表征阻止其他中间神经元节律的机制。目标 4 将研究在胆碱能受体激活不存在和存在的情况下，EC 输入对海马 CA1 中间神经元特定亚群产生节律的影响。。