Studies reveal the mechanisms behind tumor metastasis and how to stymie it. But primary tumors still get the lion’s share of researchers’ attention.
Image courtesy of Science Source/Phanie.
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
Edited by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved October 19, 2018 (received for review June 14, 2018)
Significance
Spatial learning and memory are hippocampal functions that emerge and mature during early postnatal development. The molecular mechanisms which shape this process are largely unknown. Here, we present evidence that the activity-regulated gene Arc/Arg3.1 is transiently up-regulated in the hippocampus of neonatal mice where it is required for establishing appropriate hippocampal network activity essential for spatial learning. Once established, network activity supports normal spatial learning in the absence of Arc/Arg3.1 while long-term memory storage continues to rely on Arc/Arg3.1 expression throughout life. These results demonstrate that hippocampal networks undergo a critical period of development mediated by Arc/Arg3.1 and open opportunities to investigate normal and pathological neurodevelopment of higher brain functions.
Abstract
During early postnatal development, sensory regions of the brain undergo periods of heightened plasticity which sculpt neural networks and lay the foundation for adult sensory perception. Such critical periods were also postulated for learning and memory but remain elusive and poorly understood. Here, we present evidence that the activity-regulated and memory-linked gene Arc/Arg3.1 is transiently up-regulated in the hippocampus during the first postnatal month. Conditional removal of Arc/Arg3.1 during this period permanently alters hippocampal oscillations and diminishes spatial learning capacity throughout adulthood. In contrast, post developmental removal of Arc/Arg3.1 leaves learning and network activity patterns intact. Long-term memory storage continues to rely on Arc/Arg3.1 expression throughout life. These results demonstrate that Arc/Arg3.1 mediates a critical period for spatial learning, during which Arc/Arg3.1 fosters maturation of hippocampal network activity necessary for future learning and memory storage.
Footnotes
↵1X.G., S.C.-G., and J.G. contributed equally to this work.
↵2Present address: Department of Neurodegenerative Diseases & Geropsychiatry, University Hospital Bonn, 53127 Bonn, Germany.
- ↵3To whom correspondence may be addressed. Email: kuhl{at}zmnh.uni-hamburg.de or ora.ohana{at}zmnh.uni-hamburg.de.
Author contributions: D.K. and O.O. designed research; X.G., S.C.-G., J.G., S.G., U.S., L.B., D.M., and D.I. performed research; X.G., S.C.-G., J.G., D.I., D.K., and O.O. analyzed data; and X.G., S.C.-G., J.G., D.K., and O.O. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1810125115/-/DCSupplemental.
Published under the PNAS license.
Log in using your username and password
Purchase access
You may purchase access to this article. This will require you to create an account if you don't already have one.
Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks
More Articles of This Classification
Biological Sciences
Related Content
Cited by...
- No citing articles found.
Similar Articles
You May Also be Interested in
Both social and engineering factors must be further explored and scrutinized across the globe—as should notions of justice related to flooding impacts and responses.
Image courtesy of Shutterstock.com/Ekaterina Pokrovsky.
Blair Hedges discusses the state of Haiti's remaining forests and the consequences to biodiversity.
A study uncovers genetic evidence of early colonization of Jamaica by primates and suggests that adaptation can shape species morphology in novel environments, even when species come from morphologically conservative families.
Image courtesy of Lorraine Meeker (American Museum of Natural History, New York).
Researchers report that some moth species use sound absorbing-scales to avoid detection by bats and suggest that the findings could aid the design of biologically inspired sound absorbers for an array of applications, including noise mitigation and building acoustics.
Image courtesy of Thomas R. Neil.
