Back to Search
Start Over
Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance.
- Source :
-
Nature neuroscience [Nat Neurosci] 2013 Jun; Vol. 16 (6), pp. 698-705. Date of Electronic Publication: 2013 Apr 28. - Publication Year :
- 2013
-
Abstract
- Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase-cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects.
- Subjects :
- Animals
Behavior, Animal drug effects
Behavior, Animal physiology
Cerebral Cortex cytology
Cerebral Cortex drug effects
Cerebral Cortex metabolism
Female
Glucocorticoids administration & dosage
Learning drug effects
Male
Mice
Mice, Knockout
Neuronal Plasticity drug effects
Time Factors
Cerebral Cortex physiology
Circadian Rhythm physiology
Dendritic Spines metabolism
Glucocorticoids pharmacology
Learning physiology
Neuronal Plasticity physiology
Signal Transduction physiology
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1726
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 23624512
- Full Text :
- https://doi.org/10.1038/nn.3387