Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory

Kwapis, Janine L.; Alaghband, Yasaman; Kramár, Enikö A.; López, Alberto J.; Ciernia, Annie Vogel; White, André O.; Shu, Guanhua; Rhee, Diane; Michael, Christina M.; Montellier, Emilie; Liu, Yu; Magnan, Christophe; Chen, Siwei; Sassone–Corsi, Paolo; Baldi, Pierre; Matheos, Dina P.; Wood, Marcelo A.

doi:10.1038/s41467-018-05868-0

Cited by 133 publications

(146 citation statements)

References 66 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…Using enrichment network analysis after annotating the upregulated DEGs through the KEGG pathway database, we found that the most significant change occurred in the MAPK signaling pathway (also known as the Ras-Raf-MEK-ERK pathway) (Fig 3c). Circadian genes have recently been shown to be involved in hippocampus-dependent memory (56,57), and the lack of functional Per1 in the hippocampus impairs object location memory (58) and LTP (59). As predicted, based upon the downregulation of circadian pathways we observed after learning in CBP KIX/KIX mice, we also found pathways related to circadian rhythm and circadian entrainment to be upregulated following spatial learning in WT mice.…”

Section: Spatial Learning Induces Cbp Downstream Genes In Wt Micesupporting

confidence: 79%

“…Recent evidence suggests that circadian rhythm disruptions may contribute to increased risk or aggravate disease pathology for neurodegenerative diseases including Alzheimer's disease and Parkinson's disease (106)(107)(108)(109)(110)(111). Additionally, recent research suggests that hippocampal Per1 specifically may be critical to age-related cognitive impairments (58). The CBP KIX domain appears to represent a potential target for understanding the effects of circadian and memory impairments that occur with aging.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The CBP KIX domain regulates long-term memory and circadian activity

Chatterjee

Angelakos

Bahl

et al. 2020

Preprint

View full text Add to dashboard Cite

CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBP KIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBP KIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBP KIX/KIX mice.With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBP KIX/KIX mice. CBP KIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

show abstract

Section: Spatial Learning Induces Cbp Downstream Genes In Wt Micesupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

The CBP KIX domain regulates long-term memory and circadian activity

Chatterjee

Angelakos

Bahl

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Dynamic phase relationships of molecular clock components outside the SCN have yet to be explored but may be important for subsequent physiological changes. For example, acquisition of object location memory induces Per1 expression in hippocampus, and Per1 induction is required for long‐term memory formation (Kwapis et al., ). Given the complex circuitry in each brain region, the phase and coupling strength of the molecular clock in specific cell types is also likely to affect electrical activity and thus, circuit function.…”

Section: Conclusion: Areas Of Future Investigationmentioning

confidence: 99%

Circadian regulation of membrane physiology in neural oscillators throughout the brain

Paul

Davis

Goode

et al. 2019

Eur J of Neuroscience

View full text Add to dashboard Cite

Twenty‐four‐hour rhythmicity in physiology and behavior are driven by changes in neurophysiological activity that vary across the light–dark and rest‐activity cycle. Although this neural code is most prominent in neurons of the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus, there are many other regions in the brain where region‐specific function and behavioral rhythmicity may be encoded by changes in electrical properties of those neurons. In this review, we explore the existing evidence for molecular clocks and/or neurophysiological rhythms (i.e., 24 hr) in brain regions outside the SCN. In addition, we highlight the brain regions that are ripe for future investigation into the critical role of circadian rhythmicity for local oscillators. For example, the cerebellum expresses rhythmicity in over 2,000 gene transcripts, and yet we know very little about how circadian regulation drives 24‐hr changes in the neural coding responsible for motor coordination. Finally, we conclude with a discussion of how our understanding of circadian regulation of electrical properties may yield insight into disease mechanisms which may lead to novel chronotherapeutic strategies in the future.

show abstract

“…Although young C57BL/6J mice reliably show robust long‐term memory following a 10‐min OLM training session (Kwapis et al., ; McQuown & Wood, ; Vogel‐Ciernia et al., ; Current Protocols article: Vogel‐Ciernia & Wood, ), other strains and ages may need more training. For example, we have previously shown that OLM is impaired in 18‐month‐old C57BL/6J mice (Kwapis et al., ). In order to study memory updating in these mice, we increased the amount of training from one 10‐min session to three 10‐min sessions (one session per day for 3 days) and verified that old mice successfully learn the original object locations under this increased training protocol (Kwapis et al., ).…”

Section: Commentarymentioning

confidence: 99%

Investigating Memory Updating in Mice Using the Objects in Updated Locations Task

2020

Self Cite

View full text Add to dashboard Cite

In the laboratory, memory is typically studied as a de novo experience, in which a naïve animal is exposed to a discrete learning event that is markedly different from its past experiences. Most real‐world memories, however, are updates—modifications or additions—to existing memories. This is particularly true in the aging, experienced brain. To better understand memory updating, we have developed a new behavioral paradigm called the objects in updated locations (OUL) task. OUL relies on hippocampus‐dependent spatial learning and has the advantage of being able to test both the original memory and the updated information in a single test session. Further, OUL relies on incidental learning that avoids unnecessary stress that might hinder the performance of aging animals. In OUL, animals first learn the location of two identical objects in a familiar context. This memory is then updated by moving one object to a new location. Finally, to assess the animals’ memory for the original and the updated information, all animals are given a test session in which they are exposed to four copies of the object: two in the original training locations, one in the updated location, and one in a novel location. By comparing exploration of the novel location to the familiar locations, we can infer whether the animal remembers the original and updated object locations. OUL is a simple but powerful task that could provide new insights into the cellular, circuit‐level, and molecular mechanisms that support memory updating. © 2020 by John Wiley & Sons, Inc.

show abstract

Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory

Cited by 133 publications

References 66 publications

The CBP KIX domain regulates long-term memory and circadian activity

The CBP KIX domain regulates long-term memory and circadian activity

Circadian regulation of membrane physiology in neural oscillators throughout the brain

Investigating Memory Updating in Mice Using the Objects in Updated Locations Task

Contact Info

Product

Resources

About