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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

基本信息

批准号：
10891888
负责人：
GINA G TURRIGIANO
金额：
$ 10.49万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-30
项目状态：
已结题

项目摘要

PROJECT SUMMARY 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 hyperexcitablity 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.

项目总结

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion.

DOI：
10.3389/fncel.2022.854315
发表时间：
2022
期刊：
Frontiers in cellular neuroscience
影响因子：
5.3
作者：
Ramos R;Wu CH;Turrigiano GG
通讯作者：
Turrigiano GG

CaMKIV Signaling Is Not Essential for the Maintenance of Intrinsic or Synaptic Properties in Mouse Visual Cortex.

CaMKIV 信号传导对于维持小鼠视觉皮层的内在或突触特性并不重要。

DOI：
10.1523/eneuro.0135-21.2021
发表时间：
2021
期刊：
eNeuro
影响因子：
3.4
作者：
Trojanowski,NicholasF;Turrigiano,GinaG
通讯作者：
Turrigiano,GinaG

Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex.

小鼠初级视觉皮层稳态可塑性的发育调节。

DOI：
10.1523/jneurosci.1200-21.2021
发表时间：
2021
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Wen,Wei;Turrigiano,GinaG
通讯作者：
Turrigiano,GinaG