Dissecting circuits underlying loss of control relevant to binge eating

剖析与暴饮暴食相关的失控回路

基本信息

项目摘要

ABSTRACT Obesity is a critical public health problem associated with substantial morbidity and mortality. Binge eating (BE), a compulsive episodic overeating behavior, is associated with increased rates of obesity and weight gain. Despite the negative impact of BE on physiological health and obesity risk, the underlying neural mechanisms contributing to BE are largely unknown. Loss of control (LOC) over eating - i.e., being unable to control the quantity of food consumed - is a core feature of BE and a significant predictor of obesity. However, there have been no mechanistic investigations of in vivo neural activity patterns underlying LOC during BE, limiting development of new treatments. LOC is associated with difficulties disengaging from eating (i.e., feeding offset), and pre-clinical models are an optimal system to precisely measure this behavioral event. In this set of integrated training and scientific Aims, the candidate will identify neural correlates of feeding offset using an animal model for BE to understand the underlying neural substrates of LOC. Data in mice show that activity in dorsolateral striatum (DLS), a key region associated with behavior cessation, is blunted at feeding offset after chronic BE. Preliminary data also suggest that activity in secondary motor cortex (M2) to DLS projecting cells is reduced prior to feeding offset. This project will examine the role of DLS and M2 to DLS projecting cells in feeding offset using a robust behavioral paradigm for binge eating in mice. The overarching hypotheses are: 1) D1 and D2 spiny projection neurons in DLS will differentially contribute to feeding offset in BE vs. non-BE mice; 2) reversing blunted DLS activity in BE mice via closed-loop stimulation will improve pathologic behavior; 3) specific ensembles of M2 to DLS projecting cells tuned to feeding offset will be less active in BE mice; and 4) increasing activity of M2 to DLS specific neurons will improve maladaptive feeding behavior. Cellular resolution in vivo calcium imaging will be used to identify neural activity patterns in specific DLS cell populations during feeding offset (Aim 1). Closed-loop optogenetics will be used determine whether manipulation of neural activity in DLS cell populations facilitates changes in feeding offset (Aim 2). Finally, in vivo calcium imaging and optogenetics will be used to identify, track, and manipulate M2 to DLS projecting cells at feeding offset in BE and non-BE mice to investigate a potential cortical treatment target for non-invasive treatment of BE (Aim 3). The integrated training plan will ensure the candidate achieves her career goal of developing an independent program in translational BE and obesity research. The candidate will expand her training in 4 core areas: 1) learn cellular resolution in vivo calcium imaging; 2) develop statistical analysis skills applicable to complex neural data aligned to behavioral events; 3) apply circuit manipulation techniques to inform future treatment interventions; and 4) refine measurement of novel BE behaviors to maximize translational impact. Completion of this K08 will contribute to a program of research that will increase our understanding of how core circuits underlying BE can be manipulated to minimize maladaptive feeding that contributes to obesity risk.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Britny Hildebrandt其他文献

Britny Hildebrandt的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Britny Hildebrandt', 18)}}的其他基金

Dissecting corticostriatal circuitry underlying chronic binge eating
剖析慢性暴饮暴食背后的皮质纹状体回路
  • 批准号:
    10226723
  • 财政年份:
    2021
  • 资助金额:
    $ 16.25万
  • 项目类别:
Dissecting corticostriatal circuitry underlying chronic binge eating
剖析慢性暴饮暴食背后的皮质纹状体回路
  • 批准号:
    9795363
  • 财政年份:
    2018
  • 资助金额:
    $ 16.25万
  • 项目类别:

相似海外基金

Research on the pathophysiology of acute transient psychosis using animal model
急性短暂性精神病动物模型病理生理学研究
  • 批准号:
    22K07589
  • 财政年份:
    2022
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A new monitoring method using transpulmonary thermodilution in an animal model of acute respiratory distress syndrome.
在急性呼吸窘迫综合征动物模型中使用经肺热稀释的新监测方法。
  • 批准号:
    21K16596
  • 财政年份:
    2021
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Testing existing and new therapeutic interventions in a novel animal model of acute Spot Positive intracranial hemorrhage
在急性斑点阳性颅内出血的新型动物模型中测试现有和新的治疗干预措施
  • 批准号:
    342058
  • 财政年份:
    2016
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Operating Grants
Development of a gene therapy approach to treat acute lung injury using a preclinical, large animal model
使用临床前大型动物模型开发治疗急性肺损伤的基因治疗方法
  • 批准号:
    9044084
  • 财政年份:
    2016
  • 资助金额:
    $ 16.25万
  • 项目类别:
Effect of Stem Cells derived from Human Exfoliated Decidious Teeth in animal model of acute liver failure-correlation between inflammation and regeneration in liver
人脱落乳牙干细胞在急性肝功能衰竭动物模型中的作用——肝脏炎症与再生的相关性
  • 批准号:
    15K08996
  • 财政年份:
    2015
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The search of the drug for the acute severe HBV hepatitis using animal model
动物模型寻找治疗急性重型乙型肝炎药物
  • 批准号:
    15K09003
  • 财政年份:
    2015
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A new animal model for stress-induced transition from acute to chronic pain
压力引起的急性疼痛向慢性疼痛转变的新动物模型
  • 批准号:
    9081225
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
A new animal model for stress-induced transition from acute to chronic pain
压力引起的急性疼痛向慢性疼痛转变的新动物模型
  • 批准号:
    8862455
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
Development of a animal model of acute encephalopathy and an antibody therapy
急性脑病动物模型的开发和抗体治疗
  • 批准号:
    26670500
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
A new animal model for stress-induced transition from acute to chronic pain
压力引起的急性疼痛向慢性疼痛转变的新动物模型
  • 批准号:
    9090015
  • 财政年份:
    2014
  • 资助金额:
    $ 16.25万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了