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Molecular identity, cellular physiology, and in vivo functions of nucleus accumbens astrocytes

伏隔核星形胶质细胞的分子特性、细胞生理学和体内功能

基本信息

批准号：
10316907
负责人：
Kay Elizabeth Linker
金额：
$ 7.06万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10316907
关键词：
Area Astrocytes Attenuated BRAIN initiative Barium Behavior Brain Brain Diseases Brain region Calcium Signaling Cell physiology Cells Corpus striatum structure Cues DR1 gene Data Dopamine Dopamine Antagonists Dopamine Receptor Dorsal Electrophysiology (science)Etiology Event Exhibits G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Genetic Goals Heterogeneity Hippocampus (Brain)Immunohistochemistry Intervention Investigation Lateral Learning Location Maps Measures Mediating Membrane Membrane Potentials Molecular Morphology Neuroglia Neurons Nucleus Accumbens Play Population Property Proteomics Pump Regulation Resolution Rewards Role Series Signal Transduction Slice Stimulus Transcript Ventral Striatum brain health cell type classical conditioning designer receptors exclusively activated by designer drugs experimental study in vivo insight motivated behavior neural circuit patch clamp protein expression response reward processing single cell sequencing tool transcriptomics

项目摘要

Project Summary / Abstract Astrocytes are pervasive throughout the CNS and are the most abundant non-neuronal cell type. They are an essential component of neural circuits, and increasing evidence demonstrates they are specialized for specific brain regions. For example, proteomic, transcriptomic, and electrophysiology experiments show that hippocampal and striatal astrocytes are distinct. However, it is unknown if astrocytes are heterogeneous within brain regions such as the striatum where neuronal subtypes are largely uniform. Thus, the dorsal lateral striatum (DLS) and the nucleus accumbens (NAc) receive different afferents, extend different efferents, and encode different behaviors, and yet there is no basic understanding of astrocyte heterogeneity within striatal areas. My pilot data demonstrate that NAc astrocytes have different morphologies compared to DLS astrocytes, and single- cell sequencing molecularly identified 5 astrocyte subtypes in the striatum. In Aim 1, I will extend these findings and use spatial transcriptomics and RNAscope to identify the location of each striatal astrocyte subtype. This unbiased approach will determine if astrocyte subtypes are localized to subregions of the striatum. Ventral striatal astrocytes are also functionally distinct from dorsal striatal astrocytes, as NAc astrocytes have a significantly stronger intracellular Ca2+ signaling response to dopamine than do dorsal astrocytes. Dopamine (DA) in the NAc is critical for reward-learning such as Pavlovian conditioning. In Aim 2, I will therefore determine if the distinct NAc Ca2+ responses are functionally relevant to DA-encoded Pavlovian stimulus-reward learning. Together, this project proposes a comprehensive investigation of striatal astrocyte heterogeneity (Aim 1 – Priority Area #1), which is essential for forming mechanistic hypotheses and determining causality of NAc astrocyte Ca2+ signaling in DA-encoded reward learning (Aim 2 – Priority Area #4).

项目摘要/摘要