Homeostatic plasticity mechanisms regulate behavior in vivo

稳态可塑性机制调节体内行为

• 批准号: 10579955
• 负责人: Joseph M Santin
• 金额: $ 38.44万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579955
• 关键词: Adaptive Behaviors; Address; Adult; Air; Alzheimer' s Disease; Animals; Behavior; Bioinformatics; Biological Models; Brain; Brain Stem; Breathing; Cells; Compensation; Data; Disease; Electromyography; Electrophysiology (science); Ensure; Environment; Epilepsy; Exhibits; Failure; Funding Opportunities; Gene Expression; Goals; Ice Cover; Individual; Intrinsic drive; Life; Link; Longevity; Lung; Measures; Memory; Modeling; Modernization; Molecular; Motor; Motor Neurons; Nature; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Output; Performance; Physiological; Physiology; Population; Potassium Channel; Prevalence; Process; Pump; Rana; Regulation; Research; Shapes; Stimulus; Synapses; Synaptic plasticity; System; Temperature; Testing; Time; Walking; Water; Work; candidate identification; cold temperature; extracellular; gene regulatory network; improved; in vivo; innovation; insight; motor behavior; nervous system disorder; neural; neuromuscular function; neuron component; patch clamp; programs; respiratory; response; santin; single-cell RNA sequencing; trait; ventilation

Abstract A remarkable trait of the healthy brain is that it can generate stable behaviors that last for decades. When this fails to occur, a range of neurological disorders follow. An emerging view is that neurons can sense disturbances in their activity and then make compensatory adjustments to stabilize their function, a process referred to broadly as “homeostatic plasticity.” Insights into homeostatic plasticity have improved our understanding of how neurons may remain stable in an ever-changing environment. Despite much progress, how these mechanisms work in the intact brain to produce behaviors across the lifespan remains largely unknown, and therefore, represents a major gap in basic neurobiology. We address this issue using an innovative model where there exists a direct relationship between homeostatic compensation in neurons and regulation of a tractable behavior during adult life: the respiratory motor system in frogs. For long periods each year, motor circuits that control breathing in these animals are inactive because they hibernate in water and do not breathe air. Our group recently discovered this environment leads to compensatory changes in motoneurons that allow the circuit to work appropriately when animals must breathe again after months of inactivity, thereby linking plasticity that stabilizes neuronal function to a vital and tractable behavior. Here, we exploit this system to test three hypotheses that address the central question of how homeostatic mechanisms arise in vivo to support adaptive behavior. Based on our preliminary data, we hypothesize that (1) this network relies on multiple forms of intrinsic and synaptic motor plasticity to generate appropriate output, (2) intrinsic and synaptic compensation follow unique time courses during inactivity due to distinct gene regulatory networks, and (3) activity and environmental stimuli interact to differentially regulate intrinsic and synaptic compensation. These hypotheses will be tested with an integrative approach that blends patch clamp electrophysiology to measure plasticity at the cellular level, single-cell RNA sequencing and quantitative PCR to link gene expression to physiology, electromyography to measure neuromuscular function in vivo, and extracellular recording to assess function of intact circuits. Overall, this work will inform how neurons integrate multiple types of plasticity to produce essential behaviors, a goal that must be achieved to understand how circuit function remains healthy throughout life in many individuals but fails in others to cause disease.

摘要

项目成果

Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress.

NMDA 受体功能特性的可塑性提高了网络在严重能量压力下的稳定性。

• DOI: 10.1101/2023.01.19.524811
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Bueschke,Nikolaus;Amaral-Silva,Lara;Hu,Min;Alvarez,Alvaro;Santin,JosephM
• 通讯作者: Santin,JosephM

Molecular profiling of CO2/pH-sensitive neurons in the locus coeruleus of bullfrogs reveals overlapping noradrenergic and glutamatergic cell identity.

牛蛙蓝斑中 CO2/pH 敏感神经元的分子分析揭示了去甲肾上腺素能和谷氨酸能细胞身份的重叠。

• DOI: 10.1016/j.cbpa.2023.111453
• 发表时间: 2023
• 期刊: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology
• 作者: Amaral-Silva,Lara;Santin,JosephM
• 通讯作者: Santin,JosephM

Neuron populations use variable combinations of short-term feedback mechanisms to stabilize firing rate.

神经元种群使用短期反馈机制的可变组合来稳定发射率。

• DOI: 10.1371/journal.pbio.3001971
• 发表时间: 2023-01
• 期刊: PLoS biology
• 影响因子: 9.8

Activation of respiratory-related bursting in an isolated medullary section from adult bullfrogs.

• DOI: 10.1242/jeb.245951
• 发表时间: 2023-09-15
• 期刊: The Journal of experimental biology