Inhibitory Regulation of Neural Circuit Plasticity in Visual Cortex

视觉皮层神经回路可塑性的抑制调节

基本信息

批准号：
10468236
负责人：
Joshua Trachtenberg
金额：
$ 39.75万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468236
关键词：
Acetylcholine Address Adolescent Adult Affect Amblyopia Animal Model Apical Arousal Atrophic Blindness Brain Calcium Cataract Cells Characteristics Contralateral D Cells Data Dendrites Disease Electrophysiology (science)Eye Functional Regeneration Glaucoma Goals Growth Injury Interneurons Ipsilateral Knowledge Learning Maps Measures Mediating Mus Natural regeneration Nerve Degeneration Neuraxis Neurons Ocular Dominance Optic Nerve Parvalbumins Pathway interactions Property Pyramidal Cells Recovery Research Personnel Role Slice Somatostatin Synapses Synaptic plasticity Testing Thalamic structure Therapeutic Vasoactive Intestinal Peptide Vision Disorders Visual Visual Cortex Work area striata basal forebrain base cholinergic common treatment critical period effectiveness evaluation effectiveness testing experimental study hippocampal pyramidal neuron improved in vivo inhibitory neuron monocular deprivation nerve injury neural circuit neuronal cell body neuroregulation novel novel strategies postnatal development receptive field relating to nervous system response therapy outcome two photon microscopy vision development

项目摘要

Project Summary The proposed work addresses a problem highlighted by the NEI Audacious Goals Initiative as “essential to resolve”: identifying ways to regenerate damaged neurons and promote their reconnection to the correct targets in the central nervous system. In mice, a crushed optic nerve can be regenerated by concurrent manipulation of growth-control pathways and neural activity. Yet these regenerating optic nerves may not form appropriate connections because they grow into an atrophied thalamus whose inputs to cortex are weakened. Thus, functional regeneration requires strengthening of thalamocortical inputs representing the damaged eye to re- establish binocular mapping of visual space onto cortical circuits. Similar challenges are faced in early postnatal development, when a weak incoming input from the ipsilateral eye must match the mapping laid down in a cortex already dominated by the contralateral eye. This proposal examines the circuit mechanisms in primary visual cortex necessary for successful regeneration and integration of weak inputs in primary visual cortex, using in- vivo two-photon microscopy of calcium activity in alert mice and whole-cell slice electrophysiology, and then tests the effectiveness of inducing similar conditions in adulthood. The overall hypothesis is that compartmentalized dendritic activity promotes large-scale integration of new inputs into primary visual cortex. Preliminary data suggest that direct cholinergic input to one class of inhibitory neurons, the regular-spiking, somatostatin- expressing interneurons that inhibit dendrites, is lost as the critical period closes, leading these neurons to shift from compartmentalized dendritic activity to more synchronous activity. Chemogenetic control of somatostatin interneurons will be used to promote dendritic compartmentalization in adult cortex and to test whether this enhances regeneration. These experiments are expected to reveal new mechanisms that explain how the closure of a critical period in visual development reduces the capacity for establishment and strengthening of synaptic connections in cortex. In the long term, this knowledge is likely to promote incorporation of weak inputs onto their appropriate targets during regeneration after injury or disease in adulthood, which would achieve a key goal of the NEI and improve treatment options for vision loss.

项目摘要拟议的工作解决了Nei Audious目标倡议强调的问题，这是“对于解决”：确定方法来再生受损神经元并促进其重新连接到正确的目标在小鼠中，可以通过同时操纵来再生碎神经生长控制途径和神经活动。然而，这些再生视神经可能无法形成适当的连接是因为它们成长为萎缩的丘脑，其对皮质的输入被削弱。那，功能再生需要加强代表受损眼的丘脑皮质输入将视觉空间的双目映射到皮层圆圈上。早期产后面临类似的挑战开发，当来自同侧眼的弱输入输入必须与皮层中放置的映射相匹配已经由对侧眼主导。该提案检查了主要视觉的电路机制成功修订和整合一级视觉皮层中弱输入所必需的皮层，并使用in- 警报小鼠和全细胞切片电生理学中钙活性的体内两光子显微镜，然后进行测试在成年期间诱发类似条件的有效性。总体假设是分隔树突活性促进了将新输入大规模整合到主要视觉皮层中。初步数据建议对一类抑制性神经元的直接胆碱能输入，常规刺激性，生长抑素 - 表达抑制树突的中间神经元随着关键时期的关闭而丢失，导致这些神经元转移从分区化的树突活性到更同步活性。生长抑素的化学发生中间神经元将用于促进成年皮层中的树突隔室化，并测试是否增强再生。这些实验有望揭示新的机制，以解释关闭视觉发展的关键时期可降低建立和增强的能力皮质中的突触连接。从长远来看，这些知识可能会促进弱输入的影响在成年后受伤或疾病后再生期间的适当目标，这将达到 NEI和改进治疗方案的关键目标是视力丧失。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Development of Receptive Field Tuning Properties in Mouse Binocular Primary Visual Cortex.

小鼠双眼初级视觉皮层感受野调节特性的发展。

DOI：
10.1523/jneurosci.1702-21.2022
发表时间：
2022
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Tan,Liming;Ringach,DarioL;Trachtenberg,JoshuaT
通讯作者：
Trachtenberg,JoshuaT

Parvalbumin Interneurons: All Forest, No Trees.