Experience Recruits MSK1 to Expand the Dynamic Range of Synapses and Enhance Cognition
Autor: | J. Simon C. Arthur, Daniel D. Cooper, Bruno G. Frenguelli, Daniel Hebenstreit, Marianthi Tsogka, Lorenzo Morè, Philippa Richardson, Lucia Privitera |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway cognition Male MSK1 B140 Dendritic Spines EGR1 BF Biology Hippocampus Ribosomal Protein S6 Kinases 90-kDa Synaptic Transmission 03 medical and health sciences transcriptomics Mice 0302 clinical medicine Neurotrophic factors Animals Protein kinase A Research Articles Spatial Memory Environmental enrichment Arc (protein) Neuronal Plasticity Mechanism (biology) General Neuroscience QH Long-term potentiation QP 030104 developmental biology BDNF Memory Short-Term plasticity Gene Knockdown Techniques Synapses environmental enrichment Neuroscience 030217 neurology & neurosurgery Cellular/Molecular |
Zdroj: | The Journal of Neuroscience |
ISSN: | 1529-2401 0270-6474 |
Popis: | Experience powerfully influences neuronal function and cognitive performance, but the cellular and molecular events underlying the experience-dependent enhancement of mental ability have remained elusive. In particular, the mechanisms that couple the external environment to the genomic changes underpinning this improvement are unknown. To address this, we have used male mice harboring an inactivating mutation of mitogen- and stress-activated protein kinase 1 (MSK1), a brain-derived neurotrophic factor (BDNF)-activated enzyme downstream of the mitogen-activated protein kinase (MAPK) pathway. We show that MSK1 is required for the full extent of experience-induced improvement of spatial memory, for the expansion of the dynamic range of synapses, exemplified by the enhancement of hippocampal long-term potentiation (LTP) and long-term depression (LTD), and for the regulation of the majority of genes influenced by enrichment. In addition, and unexpectedly, we show that experience is associated with an MSK1-dependent downregulation of key MAPK and plasticity-related genes, notably of EGR1/Zif268 and Arc/Arg3.1, suggesting the establishment of a novel genomic landscape adapted to experience. By coupling experience to homeostatic changes in gene expression MSK1, represents a prime mechanism through which the external environment has an enduring influence on gene expression, synaptic function, and cognition. SIGNIFICANCE STATEMENT Our everyday experiences strongly influence the structure and function of the brain. Positive experiences encourage the growth and development of the brain and support enhanced learning and memory and resistance to mood disorders such as anxiety. While this has been known for many years, how this occurs is not clear. Here, we show that many of the positive aspects of experience depend on an enzyme called mitogen- and stress-activated protein kinase 1 (MSK1). Using male mice with a mutation in MSK1, we show that MSK1 is necessary for the majority of gene expression changes associated with experience, extending the range over which the communication between neurons occurs, and for both the persistence of memory and the ability to learn new task rules. |
Databáze: | OpenAIRE |
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