Dynamics of Kv channel function in identified populations of pyramidal neurons in neocortex

新皮质锥体神经元群体中 Kv 通道功能的动态变化

• 批准号: 10335207
• 负责人: Robert C Foehring
• 金额: $ 46.65万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335207
• 关键词: Action Potentials; Anesthesia procedures; Attention; Axon; Behavior; Cells; Central Nervous System Diseases; Cerebral cortex; Charge; Closure by clamp; Code; Coupled; Dendrites; Devices; Distal; Down-Regulation; ETV1 gene; Electrophysiology (science); Elements; Epilepsy; Foundations; Frequencies; Generations; Goals; Gramicidin; Individual; Injections; Ion Channel; Kinetics; Learning; Long-Term Depression; Long-Term Potentiation; Memory; Molecular; Morphology; Motor; Neocortex; Neurons; Noise; Output; Pathologic; Pattern; Perfusion; Periodicity; Physiological; Population; Potassium; Potassium Channel; Predisposition; Process; Property; Protocols documentation; Pyramidal Tracts; Regulation; Research; Rodent; Role; Seizures; Signal Pathway; Signal Transduction; Spain; Stimulus; Structure; Sum; Synapses; Testing; Time; Training; Transgenic Mice; Up-Regulation; Work; base; biophysical properties; cell cortex; conditioning; design; experimental study; hippocampal pyramidal neuron; imaging system; in vivo; information processing; insight; neocortical; neuronal cell body; neuronal excitability; postsynaptic; relating to nervous system; response; somatosensory; tool; transmission process; two-photon; voltage

Our research is aimed at elucidating how ion channels regulate the processing of information by neurons in the cerebral cortex, i.e., the diverse mechanisms neurons use to convert synaptic input into action potentials. The proposed experiments will determine basic principles of how voltage-gated potassium (Kv) channels regulate postsynaptic processing of inputs in layer 5 (L5) neocortical pyramidal neurons (PNs). PNs are the output cells of cortex and key players in learning, memory, and sensorimotor processing, as well as the targets of central nervous system diseases (e.g., epilepsy). The proposed studies go beyond the standard notion that potassium channels act as an intrinsic brake on excitability. They are designed to determine the influence Kv2 and Kv7 channels have on the types of information that L5 PNs respond to and how that information is filtered before downstream transmission. We will study mechanisms controlling firing behavior in two classes of pyramidal neurons: intratelencephalic-projecting (IT) and pyramidal tract (PT) type, represented by two genetically-identified PNs with GFP expressed in populations of L5 PNs under control of unique genes: etv1 (IT) and thy1 (PT). We will test hypotheses concerning how Kv2 and Kv7 channels regulate burst firing (Aim 1) and continuous firing (repetitive bursting and suprathreshold resonance: Aim 2). Kv channel properties and expression are dynamic. They can undergo plastic changes in response to activity or signaling pathways and thus change neuronal filtering properties. Thus, we will also study use-dependent plasticity of intrinsic excitability (Aim 3). We use transgenic mouse lines and state-of-the-art electrophysiological approaches, including somatic / dendritic paired recordings, dynamic clamp, internal pipet perfusion, nucleated patch and on-cell patch recordings, as well as whole cell and gramicidin perforated patch. We also use two-photon and charge-coupled device (CCD)-based Ca2+ imaging systems. Our stimulus protocols are designed to mimic natural synaptic activity arriving at the soma of a neuron (the common summing point for all dendrites) and will be systematically varied to simulate different levels or composition of inputs. Our findings will have major implications for cortical processing, ion channel function, understanding neural computations, and mechanisms underlying epilepsy, anesthesia, learning and memory.

我们的研究旨在阐明离子通道如何调节神经元在 大脑皮层，即神经元用于将突触输入转化为动作电位的多种机制。这 提出的实验将确定电压门控钾（KV）通道调节的基本原理 在第5层（L5）新皮层神经元（PNS）中的输入后的突触后处理。 PNS是输出单元 在学习，记忆和感觉运动处理中的皮质和主要参与者以及中央的目标 神经系统疾病（例如癫痫）。拟议的研究超出了钾的标准概念 通道对兴奋性充当固有的制动器。它们旨在确定KV2和KV7的影响 频道对L5 PNS响应的信息类型以及如何过滤该信息 下游传输。我们将研究控制两类金字塔的发射行为的机制 神经元：脑内预测（IT）和锥体道（PT）类型，由两个遗传鉴定的PN表示，具有GFP的两个遗传识别PN，在独特基因的L5 PN人群中表达：ETV1（IT）和Thy1（IT）和Thy1和Thy1 （pt）。我们将测试有关KV2和KV7通道如何调节爆炸的假设（AIM 1）和 连续射击（重复的爆发和远方的共鸣：AIM 2）。 KV通道属性和 表达是动态的。它们可以响应活动或信号通路，并且可以进行塑料变化，并且 因此改变了神经元滤波特性。因此，我们还将研究固有的使用依赖性可塑性 兴奋性（目标3）。我们使用转基因小鼠系和最先进的电生理方法， 包括体细胞 /树突配对记录，动态夹具，内部移液器灌注，成核斑块和 电池贴片记录，以及全细胞和谷霉素穿孔贴片。我们还使用两光子和 电荷耦合设备（CCD）基于CA2+成像系统。我们的刺激协议旨在模仿 天然突触活动到达神经元的躯体（所有树突的常见求和点），并将 系统地变化以模拟输入的不同级别或组成。我们的发现将有重大 对皮质处理，离子通道功能，理解神经计算和机制的影响 基础癫痫，麻醉，学习和记忆。

项目成果

Input rate encoding and gain control in dendrites of neocortical pyramidal neurons.

• DOI: 10.1016/j.celrep.2022.110382
• 发表时间: 2022-02-15
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Dembrow NC;Spain WJ
• 通讯作者: Spain WJ

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex.

• DOI: 10.1152/jn.01028.2015
• 发表时间: 2016-05
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: D. Pathak;D. Guan;R. Foehring

PIP2 alters of Ca2+ currents in acutely dissociated supraoptic oxytocin neurons.

PIP2 改变急性分离的视上催产素神经元中的 Ca2+ 电流。

• DOI: 10.14814/phy2.14198
• 发表时间: 2019
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Kirchner,MatthewK;Armstrong,WilliamE;Guan,Dongxu;Ueta,Yoichi;Foehring,RobertC
• 通讯作者: Foehring,RobertC

Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy.

钾通道调节的变化可能是妊娠晚期催产素神经元后超极化可塑性的基础。

• DOI: 10.1152/jn.00608.2017
• 发表时间: 2018
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Wang,Lie;Chandaka,GiriKumar;Foehring,RobertC;Callaway,JosephC;Armstrong,WilliamE
• 通讯作者: Armstrong,WilliamE