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Investigating the role of anterior lateral motor cortex in control and execution of sequenced behaviors

研究前外侧运动皮层在控制和执行顺序行为中的作用

基本信息

批准号：
10546498
负责人：
Susanne Elizabeth Ahmari
金额：
$ 42.34万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10546498
关键词：
Anterior Anterolateral Area Behavior Behavioral Brain Brain region Childhood Color Complex Corpus striatum structure Data Detection Drops Electrophysiology (science)Fiber Generations Gilles de la Tourette syndrome Goals Grooming Homologous Gene Human Hyperactivity Image Individual Instinct Knock-out Knockout Mice Lateral Length Link Microscopy Modeling Motor Motor Cortex Movement Neurons Obsessive-Compulsive Disorder Pattern Performance Photometry Play Preparation Prevention strategy Process Property Protocols documentation Ramp Regulation Resistance Rodent Role Slice Stereotyping Symptoms System Testing Thinking Wild Type Mouse Work autism spectrum disorder comorbidity defined contribution in vivo learned behavior maladaptive behavior motor learning neuropsychiatric disorder novel optogenetics programs public health relevance recruit sequence learning serial imaging stem theories

项目摘要

PROJECT SUMMARY/ ABSTRACT Although smoothly linking individual actions into sequences is critical for execution of complex behaviors, we still have a limited understanding of how behavioral sequences are encoded in the brain. Accumulating evidence suggests that striatal activity patterns are linked to performance of sequenced behaviors, but the role of cortical inputs in their initiation and control is less clear. We therefore used the SAPAP3-knockout (KO) mouse experimental system, which displays repetitive grooming behavior associated with central striatal (CS) hyperactivity, to investigate how cortical and striatal regions interact to generate both normal and perseverative action patterns. In our recent work, we demonstrated that SAPAP3-KOs do not have abnormalities in striatal intrinsic properties using ex vivo electrophysiology. However, we observed large (~6 fold) increases in extrinsic drive to CS from the major cortical input to this region: anterolateral motor area (ALM- also known as M2). (Corbit et al, 2019). These results suggested that repeated selection of motor programs could be caused by excessive drive from ALM, an area whose human homologues (SMA/pre- SMA) have been linked to Tourette Syndrome (TS) and OCD. Our preliminary optogenetics and photometry data support this theory by identifying ALM activity that ramps up during grooming, and terminates at grooming bout cessation. Together, these results indicate that ALM may be a key under- recognized hub for the regulation of innate sequenced behaviors. However, 1) this idea has not yet been rigorously tested, and 2) it is unclear if the same principles apply to learned sequenced behaviors. Here we will use state-dependent optogenetics, ex vivo electrophysiology, and longitudinal in vivo Ca+2 imaging to determine the role of ALM in the generation of normal and abnormal innate and learned sequenced behaviors. In Aim 1, we will Identify the ALM ensemble responsible for grooming-associated ramping activity. In Aim 2, we will determine whether increasing ALM-CS drive leads to repeated selection of innate and/or learned sequenced behaviors. In Aim 3, we will define the role of ALM activity during performance of learned sequences using in vivo microscopy and optogenetics. The goal of these studies is to determine how cortico-striatal circuits control the assembly of individual actions into organized sequences, which could ultimately lead to new neurostimulation-based treatment targets for perseverative behaviors.

项目摘要/摘要