Modulation of dendritic spiking in vivo

体内树突尖峰的调节

• 批准号: 9231511
• 负责人: SPENCER LAVERE SMITH
• 金额: $ 33.25万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231511
• 关键词: Action Potentials; Adaptive Behaviors; Address; Apical; Behavior; Behavioral; Behavioral Assay; Behavioral Mechanisms; Brain; Brain Diseases; Calcium; Complex; Dendrites; Disease; Disinhibition; Distal; Gated Ion Channel; Head; Image; Imaging technology; Interneurons; Ion Channel Gating; Knowledge; Link; Mental disorders; Modeling; Mus; N-Methyl-D-Aspartate Receptors; Neuromodulator; Neurons; Opsin; Patch-Clamp Techniques; Pathologic; Pathway interactions; Play; Process; Publishing; Regulation; Sensory; Shapes; Signal Transduction; Site; Somatostatin; Source; Synapses; System; Techniques; Testing; Transgenic Mice; Vasoactive Intestinal Peptide; Visual; Work; awake; experimental study; hippocampal pyramidal neuron; in vivo; innovation; insight; instrumentation; multiphoton imaging; nervous system disorder; neuronal cell body; neuroregulation; novel therapeutic intervention; optogenetics; patch clamp; permissiveness; public health relevance; somatosensory; two-photon; visual processing; voltage

 DESCRIPTION (provided by applicant): Cortical activity is tightly regulated to support adaptive behavior, but the mechanisms underlying this regulation are unclear. In this project, we will investigate how cortical activity is regulated in vivo, directly at the site of synaptic input Dendrites actively process synaptic input using voltage-gated ion channels and NMDA receptors. We recently showed that these mechanisms support dendritic spiking in awake mice. These dendritic spikes propagate to the soma as depolarizations that can trigger conventional axonal spikes, and thus represent a layer of computational processing that contributes to neuronal selectivity. A recently elucidated circuit motif involving neuromodulation and dendrite-targeting interneurons could play a key role in regulating dendritic spiking during sensory processing and behavior. Here, we use dendritic patch clamp recordings, optogenetics, and new multiphoton imaging technology to interrogate this circuit motif, its effects on dendritic spiking, and its activity during sensory processing and behavior. Since dendritic spiking is an essential component of synaptic integration in cortical circuitry, and dysfunctional synaptic integration is implicated in complex psychiatric and neurological disorders, results from this project can eventually contribute to new therapeutic strategies.