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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.