Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization
| العنوان: | Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
|---|---|
| المؤلفون: | Austin A. Coley, Corey C. Harwell, Katherine A. Shepard, Andrew S Blaeser, Wen-Jun Gao, A. Denise R. Garcia, Ya-Jun Xie, Steven A Hill |
| المصدر: | eLife, Vol 8 (2019) eLife |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Dendritic spine, Mouse, QH301-705.5, Science, Cell, Mutant, spines, Cell Communication, Biology, General Biochemistry, Genetics and Molecular Biology, Synapse, Mice, 03 medical and health sciences, astrocyte, 0302 clinical medicine, synapse, medicine, Animals, Premovement neuronal activity, Hedgehog Proteins, Biology (General), Sonic hedgehog, development, 030304 developmental biology, Cerebral Cortex, Neurons, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, General Medicine, Hedgehog signaling pathway, Cell biology, Cortex (botany), medicine.anatomical_structure, Astrocytes, plasticity, biology.protein, Medicine, Neuroscience, 030217 neurology & neurosurgery, Research Article, Signal Transduction, Astrocyte |
| الوصف: | Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses. eLife digest A central system of neurons in the spinal cord and brain coordinate most of our body’s actions, ranging from regulating our heart rate to controlling our movement and thoughts. As the brain develops, neurons form specialized contacts with one another known as synapses. If the number of synapses is not properly regulated this can disrupt communication between the neurons, leading to diseases like schizophrenia and autism. As the brain develops, it first forms an excess of synapses and later eliminates unnecessary or weak connections. Various factors, such gene expression or a neuron’s level of activity, regulate this turnover process. However, neurons cannot do this alone, and rely on other types of cells to help regulate their behavior. In the central nervous system, for example, a cell called an astrocyte is known to support the formation and activity of synapses. Now, Hill and Blaeser et al. show that astrocytes also exert influence over synaptic turnover during development, leading to long lasting changes in the number of synapses. Hill, Blaeser et al. revealed that disrupting activity of the signaling pathway known as Sonic hedgehog, or Shh for short, in the astrocytes of mice led to disordered synaptic connections. Notably, neurons produce Shh, suggesting that neurons use this signaling pathway to communicate to specific astrocyte partners. Further experiments showed that reducing astrocyte’s ability to respond to Shh impaired synaptic turnover as the brain developed, leading to an overabundance of synapses. Importantly, these effects were only found to influence neuron populations associated with astrocytes that actively use Shh signaling. This suggests that distinct populations of neurons and astrocytes interact in specialized ways to build the connections within the nervous system. To address how astrocytes use Shh signaling to regulate synaptic turnover, Hill, Blaeser et al. examined gene expression changes in astrocytes that lack Shh signaling. Astrocytes with a reduced capacity to respond to Shh were found to have lower levels of a protein responsible for transporting potassium ions into and out of the cell. This impairs astrocyte’s ability to regulate neuronal activity, which may lead to a failure in eliminating unnecessary synapses. Understanding how synapses are controlled and organized by astrocytes could help identify new ways to treat diseases of the developing nervous system. However, further studies would be needed to improve our understanding of how this process works. |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ef16cfe17424f607a747890448cbcd6 https://doi.org/10.1101/537860 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9ef16cfe17424f607a747890448cbcd6 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |