Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 33, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2104119118
Keywords
astrocyte-derived neurogenesis; striatum; neurons; glutamatergic
Categories
Funding
- Swedish Research Council
- Swedish Brain Foundation
- Ming Wai Lau Centre for Reparative Medicine
- European Union Joint Programme -Neurodegenerative Disease (JPND) Deciphering Interactions of Acquired Risk Factors and ApoE-mediated Pathways in Alzheimer's Disease (DACAPO-AD)
- Wings for Life Foundation
- KAW Foundation
- strategic networks for neuroscience and stem cells and regenerative medicine at Karolinska Institutet
Ask authors/readers for more resources
Research has shown that inhibition of Notch signaling in astrocytes can induce adult striatal neurogenesis in the intact mouse brain. These astrocyte-derived neurons possess distinct electrophysiological properties, constituting the only glutamatergic striatal population, and have the potential to compensate for reduced neuronal activity in the striatal circuitry caused by aging or lesion-induced neuronal loss.
Astrocytes have emerged as a potential source for new neurons in the adult mammalian brain. In mice, adult striatal neurogenesis can be stimulated by local damage, which recruits striatal astrocytes into a neurogenic program by suppression of active Notch signaling (J. P. Magnusson et al., Science 346, 237-241 [2014]). Here, we induced adult striatal neurogenesis in the intact mouse brain by the inhibition of Notch signaling in astrocytes. We show that most striatal astrocyte-derived neurons are confined to the anterior medial striatum, do not express established striatal neuronal markers, and exhibit dendritic spines, which are atypical for striatal interneurons. In contrast to striatal neurons generated during development, which are GABAergic or cholinergic, most adult astrocyte-derived striatal neurons possess distinct electrophysiological properties, constituting the only glutamatergic striatal population. Astrocyte-derived neurons integrate into the adult striatal microcircuitry, both receiving and providing synaptic input. The glutamatergic nature of these neurons has the potential to provide excitatory input to the striatal circuitry and may represent an efficient strategy to compensate for reduced neuronal activity caused by aging or lesion-induced neuronal loss.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available