权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A Model for Homeostatic Plasticity in Striatum

纹状体稳态可塑性模型

基本信息

批准号：
10753789
负责人：
Deanna L Benson
金额：
$ 46.48万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
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：
2023-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10753789
关键词：
Address Adenosine Adult Animal Model Anxiety Automobile Driving Basal Ganglia Biological Calibration Cells Chronic Coculture Techniques Compensation Corpus striatum structure DRD2 gene Data Dementia Disease Disease model Dopamine Receptor Electrophysiology (science)Enterobacteria phage P1 Cre recombinase Equilibrium Future Glutamates Goals Health Impaired cognition Individual Learning Measurement Measures Mediating Membrane Modeling Molecular Morphology Mus Nature Neuromuscular Junction Neurons Pathologic Pathology Pathway interactions Recurrence Research Signal Transduction Synapses Synaptic plasticity System Testing Thalamic structure Transgenic Mice Transgenic Model Vertebral column Weight addiction cell type design dynamic system fluorophore in vitro activity in vivo learned behavior nervous system disorder neural promoter receptor response sensory system synaptic function

项目摘要

PROJECT SUMMARY Changes in synaptic weights encode new learning and the execution of learned behaviors. Such changes occur across different timescales, all within dynamic systems that recalibrate and compensate homeostatically to stabilize network activity and maintain activity within a useful dynamic range. Strong data support that these stabilizing mechanisms are conserved evolutionarily and represented across neural systems. In animal models, they have been best studied in sensory systems and at the neuromuscular junction. Despite broad acceptance of these mechanisms, the homeostatically stabilizing actions of most networks have not been documented and/or are poorly understood. A normal functioning synapse can be strengthened or weakened over fast timescales (seconds to minutes) and includes Hebbian forms of synapse plasticity such as LTP or LTD. In cortical synapses forming on striatal projection neurons (SPNs), abnormal Hebbian synaptic plasticity is a hallmark of anxiety- and addiction-like states and neurological disease models associated with cognitive impairment or dementia. Collectively, the data indicate that Hebbian plasticity is vulnerable to a variety of pathological conditions. However, the data also suggest that under such conditions, corticostriatal networks are no longer kept within a useful working range—that the adaptive actions designed to stabilize this largely closed-loop system may also be particularly vulnerable. Importantly, whether or how corticostriatal circuits adapt to sustained increases or decreases in activity is not clear, a significant lapse in understanding overall corticostriatal network function in health and disease states. The specific goals of this multi-PI R21 are to define the nature of homeostatic adaptation within SPNs. We will assess responses to widespread, targeted, and cell autonomous increases or decreases in neural activity in vitro and within an intact system. These data will permit us to build a testable model that can be used in the future for assessing how homeostatic mechanisms become maladaptive or subverted by disease-related pathologies.

项目总结