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Astrocyte-Neuron Network Activity During In Vivo Brain Stimulation

体内脑刺激期间星形胶质细胞-神经元网络活动

基本信息

批准号：
10731064
负责人：
Kevin Stieger
金额：
$ 4.77万
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：
2022-09-20 至 2024-11-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10731064
关键词：
Address Animals Astrocytes Basic Science Brain Ca(2+)-Transporting ATPase Calcium Cell membrane Cells Clinical Communication Coupled Deep Brain Stimulation Electric Stimulation Electrodes Esthesia Frequencies Funding GTP-Binding Proteins Goals Image Impairment Implant Implanted Electrodes Intervention Knowledge Microelectrodes Multimodal Imaging Mus Nervous System Physiology Neurobiology Neuroglia Neurons Neurosciences Neurosciences Research Neurostimulation procedures of spinal cord tissue Neurotransmitters Opsin Outcome Pattern Physiologic pulse Physiological Play Property Regulation Research Role Sensory Synapses Synaptic Transmission Synaptic plasticity Techniques Therapeutic Time Treatment Efficacy Viral Work adeno-associated viral vector awake career cell type clinically relevant design genetic manipulation imaging approach improved in vivo insight interest melanopsin microstimulation multimodality nervous system disorder neural neurobiological mechanism neuronal cell body neuroprosthesis neurotransmitter release novel optical imaging optogenetics response restoration sensory feedback sight for the blind sight restoration spatiotemporal stem synaptic function therapeutic target therapy outcome tool two photon microscopy two-photon

项目摘要

PROJECT SUMMARY Intracortical microstimulation (ICMS) is a primary component of fundamental neuroscience research and holds great potential for sensory restoration or sensory feedback in neuroprosthetics. Despite the wide use of electrical stimulation in neuroprosthetics and interventions such as spinal cord stimulation and deep brain stimulation (DBS), the fundamental physiological and mechanistic properties defining therapeutic efficacy remain poorly understood. For example, it is still unclear which cell types are activated, what role they play in therapeutic outcomes, and how to tune stimulation parameters to selectively elicit relevant activity in those cell types for sensory restoration. Of particular interest is the contribution of non-neuronal cells such as astrocytes. Astrocytes are emerging as important cells in the modulation of neuronal activity during sensory processing in which they respond to neurotransmitters with calcium elevations leading to the release of neuroactive substances to regulate synaptic function (i.e., gliotransmission). Importantly, the time scale in which astrocytes modulate neuronal and synaptic activity is consistent with ICMS-induced neural activity. It is because of these recently appreciated roles regarding astrocyte-neuron communication that astrocytes have been suggested as a vital component to brain stimulation. However, it is unclear how astrocytes respond to clinically relevant stimulation parameters on a network level and how that activation subsequently modulates neuronal activity in an awake animal. To address this gap in knowledge, this proposal will first quantify the calcium activity in cortical astrocytes and across a larger network induced by ICMS with different frequencies and temporal patterns known to have differential therapeutic efficacy using both two-photon microscopy and mesoscale imaging. Next, this proposal will quantify how ICMS- induced neuronal activity is modulated when astrocyte calcium activity is selectively increased (optogenetics) or decreased (viral transduction of a plasma membrane calcium pump) to determine how astrocytes regulate neuronal network activity during ICMS. Because astrocyte calcium activity regulates how these important cells modulate neuronal activity, the cumulative results of this proposal will provide valuable insight for fundamental neuroscience research and the design of stimulation paradigms to elicit astrocyte activity relevant to sensory restoration.

项目总结