Mechanisms and function of firing rate homeostasis in cortical circuits
皮质回路中放电率稳态的机制和功能
基本信息
- 批准号:9923773
- 负责人:
- 金额:$ 81.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AnimalsBackDevelopmentDiseaseEpilepsyFeedbackGoalsHomeostasisIndividualInvestigationLearningMemoryMolecularNatureNeuraxisNeuronsPost-Traumatic Stress DisordersProcessPropertyResearch SupportRoleSensorySynapsesTestingWorkautism spectrum disorderexperiencehippocampal pyramidal neuronin vivomemory encodingneocorticalnervous system disorderpreventprogramstool
项目摘要
The overall goal of my NS-supported research program is to understand the mechanisms that
stabilize the function of central nervous system (CNS) microcircuits during experience-
dependent plasticity and learning. Over the past ~20 years of NS support we discovered and
characterized several forms of homeostatic plasticity, including synaptic scaling and intrinsic
homeostatic plasticity, that are postulated to sense perturbations in mean neuronal activity,
then bidirectionally adjust synaptic and cellular properties to keep activity within a set point
range. Our recent work has focused on a) identifying the cellular and molecular mechanisms of
these homeostatic forms of plasticity in order to bolster our mechanistic and functional
understanding, and to generate tools that allow us to selectively block homeostatic plasticity in
vivo; and b) to determine what aspect of neuronal activity is under homeostatic control in intact
CNS circuits in vivo. We recently showed that the mean firing rates of neocortical pyramidal
neurons in freely behaving animals return back to an individual baseline following prolonged
perturbations to sensory drive, strongly supporting the idea that neocortical neurons
homeostatically regulate their mean firing around an individual 'firing rate set point'. Such a
process is theoretically important for preventing circuit hypo- or hyperexcitability during
experience-dependent development, as well as to short-circuit the positive feedback nature of
Hebbian plasticity rules that can degrade memory fidelity. We now have (or are developing) the
tools to disrupt homeostatic plasticity and firing rate set points in vivo, allowing us to assess the
impact of this disruption on network function and memory storage. The major goals of my NS-
supported research program going forward are: 1) to determine how activity set points are built,
and how individual neurons can have set points that are orders of magnitude different from each
other; 2) to understand how multiple homeostatic mechanisms cooperate with each other to
stabilize network activity in the face of profound perturbations; and 3) to test the role of
synaptic scaling and intrinsic homeostatic plasticity in memory encoding and generalization.
These studies will have important implications for our understanding of neurological disorders
that arise from aberrant circuit excitability (epilepsy, autism-spectrum disorders). They may
also provide a new avenue into understanding disorders such as PTSD that are likely to arise
from excessive generalization during aversive learning.
我的NS支持的研究计划的总体目标是了解
在体验过程中稳定中枢神经系统(CNS)微电路的功能-
依赖性可塑性和学习。在过去20年的NS支持中,我们发现,
具有几种形式的稳态可塑性,包括突触缩放和内在的
内稳态可塑性,被假定为感知平均神经元活动的扰动,
然后双向调节突触和细胞特性,
范围我们最近的工作集中在a)确定细胞和分子机制,
这些可塑性的稳态形式,以支持我们的机制和功能,
理解,并产生工具,使我们能够选择性地阻止稳态可塑性,
B)确定在完整的神经细胞中,神经元活动的哪个方面处于稳态控制之下,
体内CNS回路。我们最近发现,大脑皮层锥体神经元的平均放电率
自由行为动物的神经元在长时间的
扰动的感觉驱动,强烈支持的想法,新皮层神经元
在个体“放电率设定点”周围稳态地调节它们的平均放电。这样的
过程在理论上对于防止电路低兴奋性或高兴奋性是重要的,
依赖经验的发展,以及短路的积极反馈性质,
赫布可塑性规则会降低记忆的保真度。我们现在有(或正在开发)
破坏体内稳态可塑性和放电率设定点的工具,使我们能够评估
这种中断对网络功能和内存存储的影响。我的主要目标是-
未来支持的研究计划是:1)确定如何建立活动设定点,
以及单个神经元的设定点如何与每个神经元的设定点相差几个数量级
2)了解多种稳态机制如何相互合作,
稳定网络活动,以面对深刻的扰动;和3)测试的作用,
记忆编码和概括中的突触缩放和内在稳态可塑性。
这些研究将对我们理解神经系统疾病具有重要意义
由异常回路兴奋性引起(癫痫、自闭症谱系障碍)。他们可能
也提供了一个新的途径来了解疾病,如创伤后应激障碍,可能会出现
在厌恶性学习中过度泛化的结果
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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GINA G TURRIGIANO其他文献
GINA G TURRIGIANO的其他文献
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{{ truncateString('GINA G TURRIGIANO', 18)}}的其他基金
Mechanisms and Function of Firing Rate Homeostasis in Cortical Circuits
皮层回路放电率稳态的机制和功能
- 批准号:
10891888 - 财政年份:2023
- 资助金额:
$ 81.77万 - 项目类别:
Mechanisms and Function of Firing Rate Homeostasis in Cortical Circuits
皮层回路放电率稳态的机制和功能
- 批准号:
10604278 - 财政年份:2019
- 资助金额:
$ 81.77万 - 项目类别:
Mechanisms and function of firing rate homeostasis in cortical circuits
皮质回路放电率稳态的机制和功能
- 批准号:
10391451 - 财政年份:2019
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
9767198 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
10610948 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
10209082 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
9546749 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
9380563 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity
经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控
- 批准号:
10396620 - 财政年份:2017
- 资助金额:
$ 81.77万 - 项目类别:
Synaptic Homeostasis in Neocortical Neurons and Circuits
新皮质神经元和回路的突触稳态
- 批准号:
9111079 - 财政年份:2015
- 资助金额:
$ 81.77万 - 项目类别:
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