Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant
Abstract
In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted, but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles, and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.
Article and author information
Author details
Reviewing Editor
- Louis Ptáček, University of California, San Francisco, United States
Ethics
Animal experimentation: All animal care and use procedures were in accordance with guidelines of the Northwestern University (Protocol 2006-0035) and UT Southwestern Institutional Animal Care and Use Committees (Protocols 2009-0054 and 2012-0090).
Version history
- Received: September 9, 2014
- Accepted: December 18, 2014
- Accepted Manuscript published: December 19, 2014 (version 1)
- Version of Record published: January 21, 2015 (version 2)
Copyright
© 2014, Izumo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,549
- views
-
- 1,052
- downloads
-
- 130
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Genetics and Genomics
- Neuroscience
Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.
-
- Neuroscience
We are unresponsive during slow-wave sleep but continue monitoring external events for survival. Our brain wakens us when danger is imminent. If events are non-threatening, our brain might store them for later consideration to improve decision-making. To test this hypothesis, we examined whether novel vocabulary consisting of simultaneously played pseudowords and translation words are encoded/stored during sleep, and which neural-electrical events facilitate encoding/storage. An algorithm for brain-state-dependent stimulation selectively targeted word pairs to slow-wave peaks or troughs. Retrieval tests were given 12 and 36 hr later. These tests required decisions regarding the semantic category of previously sleep-played pseudowords. The sleep-played vocabulary influenced awake decision-making 36 hr later, if targeted to troughs. The words’ linguistic processing raised neural complexity. The words’ semantic-associative encoding was supported by increased theta power during the ensuing peak. Fast-spindle power ramped up during a second peak likely aiding consolidation. Hence, new vocabulary played during slow-wave sleep was stored and influenced decision-making days later.