Original Research ARTICLE
Molecular and anatomical signatures of sleep deprivation in the mouse brain
- 1 Allen Institute for Brain Science, Seattle, WA, USA
- 2 Biosciences Division, SRI International, Menlo Park, CA, USA
Sleep deprivation (SD) leads to a suite of cognitive and behavioral impairments, and yet the molecular consequences of SD in the brain are poorly understood. Using a systematic immediate-early gene (IEG) mapping to detect neuronal activation, the consequences of SD were mapped primarily to forebrain regions. SD was found to both induce and suppress IEG expression (and thus neuronal activity) in subregions of neocortex, striatum, and other brain regions. Laser microdissection and cDNA microarrays were used to identify the molecular consequences of SD in seven brain regions. In situ hybridization (ISH) for 222 genes selected from the microarray data and other sources confirmed that robust molecular changes were largely restricted to the forebrain. Analysis of the ISH data for 222 genes (publicly accessible at http://sleep.alleninstitute.org) provided a molecular and anatomic signature of the effects of SD on the brain. The suprachiasmatic nucleus (SCN) and the neocortex exhibited differential regulation of the same genes, such that in the SCN genes exhibited time-of-day effects while in the neocortex, genes exhibited only SD and waking (W) effects. In the neocortex, SD activated gene expression in areal-, layer-, and cell type-specific manner. In the forebrain, SD preferentially activated excitatory neurons, as demonstrated by double-labeling, except for striatum which consists primarily of inhibitory neurons. These data provide a characterization of the anatomical and cell type-specific signatures of SD on neuronal activity and gene expression that may account for the associated cognitive and behavioral effects.
Keywords: in situ hybridization, sleep deprivation, gene expression, microarray
Citation: Thompson CL, Wisor JP, Lee C-K, Pathak SD, Gerashchenko D, Smith KA, Fischer SR, Kuan CL, Sunkin SM, Ng LL, Lau C, Hawrylycz M, Jones AR, Kilduff TS and Lein ES (2010) Molecular and anatomical signatures of sleep deprivation in the mouse brain. Front. Neurosci. 4:165. doi: 10.3389/fnins.2010.00165
Received: 15 May 2010;
Paper pending published: 16 June 2010;
Accepted: 23 August 2010; Published online: 21 October 2010
Edited by:Paul Franken, Université de Lausanne, Switzerland
Reviewed by:Valérie Mongrain, Université de Lausanne, Switzerland
Bruce F. O’Hara, University of Kentucky, USA
Copyright: © 2010 Thompson, Wisor, Lee, Pathak, Gerashchenko, Smith, Fischer, Kuan, Sunkin, Ng, Lau, Hawrylycz, Jones, Kilduff and Lein. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Edward S. Lein, Allen Institute for Brain Science, 551 N. 34th Street, Ste. 200, Seattle, WA 98103, USA. e-mail: email@example.com