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Neural Mechanisms of Predictive Impairments in Autism

自闭症预测性障碍的神经机制

基本信息

批准号：
10660345
负责人：
Alexander Chubykin
金额：
$ 48.97万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-20 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10660345
关键词：
ASD patient Anatomy Anterior Area Behavior Behavioral Brain Code Computer Models Cortical Cell Layer Cues Data Decision Making Detection Development Discrimination Electrophysiology (science)Elements Event FMR1 FMRP Familiarity Fragile X Syndrome Frequencies Funding Future Generations Goals Grant Human Impairment In Vitro Intellectual functioning disability Interneurons Knockout Mice Learning Learning Disabilities Life Link Maps Measures Modeling Mus Neocortex Neurons Outcome Patients Pattern Process Publications Reporting Research Role Sensory Short-Term Memory Slice Social Interaction Stimulus Synapses Synaptic plasticity System Therapeutic Time Visual Visual Perception area striata autism spectrum disorder awake behavior prediction cell type cingulate cortex data modeling diagnostic criteria expectation experience extracellular feasibility research in vivo individuals with autism spectrum disorder information processing mouse model neocortical neural neural circuit neuromechanism novel optogenetics personalized medicine pharmacologic restoration selective expression sensory stimulus social communication synaptogenesis therapeutic target visual learning

项目摘要

Autism spectrum disorders (ASDs) are characterized by altered sensory processing and intellectual disability. Atypical sensory processing has been recognized as an important diagnostic criterion for autism and is predictive of social communication deficits later in life. ASDs are also associated with impaired structural and functional connectivity within and between neocortical areas. However, how impaired neural connectivity, which is present in ASDs, leads to impaired sensory processing and learning is not understood. Recently, we have discovered new visual familiarity-evoked theta oscillations in the primary visual cortex (V1). In Fmr1 KO mice, a mouse model of Fragile X syndrome, these oscillations are weaker, shorter, and frequency shifted. Furthermore, we have shown a similar emergence of visually cued theta oscillations in the anterior cingulate cortex (ACC), an area connected to V1 and involved in social interaction, decision making and error detection. We have also started mapping the neural circuit underlying these oscillations. Our prior studies suggest that these familiarity-evoked theta oscillations and the underlying changes in the neural circuit connectivity may be the cause of impairments in visual learning and perception. Our preliminary data also suggest that Fmr1 KO mice demonstrate impaired theta oscillations in a visual discrimination task. We have developed a computational model to reproduce theta oscillations in the cortex. This proposal builds on foundational advances by dissecting the mechanisms of theta oscillations in WT and Fmr1 KO mice. Using an integrated approach combining mapping of neuronal connectivity in brain slices, in vivo extracellular recordings, and behavior, we will: 1) map the circuitry necessary to form a theta oscillator in V1 and identify altered connectivity patterns within V1 and between V1 and ACC in Fmr1 KO mice, 2) examine how the strength of theta oscillations in V1 and ACC correlates with behavior in WT and Fmr1 KO mice following learning, and 3) rescue theta oscillations by restoring FMRP expression selectively only in the specific neuronal groups in Fmr1 KO mice guided by the computational model. Based on our prior studies, preliminary data, and computational model, we expect to see familiarity-evoked theta oscillations correlate with successful behavior in a visual discrimination task. We also expect to identify the critical parts of the neural circuit required for the generation of theta oscillations and its impairment in Fmr1 KO mice. Results from this proposal will help inform the development of targeted neural circuit-based behavioral and pharmacological therapeutics to enable personalized medicine for individuals with ASDs.

自闭症谱系障碍（ASDs）的特征是感觉处理和感知能力的改变

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Visual Familiarity Induced 5-Hz Oscillations and Improved Orientation and Direction Selectivities in V1.

DOI：
10.1523/jneurosci.1337-20.2021
发表时间：
2021-03-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Gao M;Lim S;Chubykin AA
通讯作者：
Chubykin AA

Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse.

DOI：
10.3389/fncel.2021.668230
发表时间：
2021
期刊：
Frontiers in cellular neuroscience
影响因子：
5.3
作者：
Pak A;Kissinger ST;Chubykin AA
通讯作者：
Chubykin AA

Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.

DOI：
10.1016/j.isci.2023.107842
发表时间：
2023-10-20
期刊：
ISCIENCE
影响因子：
5.8
作者：
Cheng, Xi;Tang, Yu;Vidyadhara, D. J.;Li, Ben-Zheng;Zimmerman, Michael;Pak, Alexandr;Nareddula, Sanghamitra;Edens, Paige Alyssa;Chandra, Sreeganga S.;Chubykin, Alexander A.
通讯作者：
Chubykin, Alexander A.

A 0.43 g Wireless Battery-Less Neural Recorder With On-Chip Microelectrode Array and Integrated Flexible Antenna.

DOI：
10.1109/lmwc.2022.3167311
发表时间：
2022-06
期刊：
IEEE MICROWAVE AND WIRELESS COMPONENTS LETTERS
影响因子：
3
作者：
Shan, Hengying;Peterson, John, III;Conrad, Nathan J.;Tang, Yu;Zhu, Yuhang;Ghotbi, Shabnam;Hathorn, Sutton;Chubykin, Alexander A.;Mohammadi, Saeed
通讯作者：
Mohammadi, Saeed

Visual experience induces 4-8 Hz synchrony between V1 and higher-order visual areas.