Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
- Johannes Gutenberg-University Mainz, Germany
- University Hospital Münster, Germany
Abstract
Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (Fa474/5)
- Cornelius Faber
Deutsche Forschungsgemeinschaft (SFB 1080)
- Albrecht Stroh
Deutsche Forschungsgemeinschaft (SFB 1193)
- Albrecht Stroh
Deutsche Forschungsgemeinschaft (SPP 1665)
- Albrecht Stroh
Focus Program translational Neurosciences
- Miriam Schwalm
- Albrecht Stroh
Interdisciplinary Center for Clinical Research Münster (Fa3/1603,PIX)
- Cornelius Faber
Excellence Cluster Cells in Motion (EXEC 1003)
- Cornelius Faber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States
Ethics
Animal experimentation: Animal husbandry and experimental manipulation were carried out according to animal welfare guidelines of the Westfalian Wilhelms-University and the Johannes Gutenberg-University Mainz and were approved by the Landesamt für Natur-, Verbraucher- und Umweltschutz Nordrhein-Westfalen, Recklinghausen, Germany (animal protocol number: 84-02.04.2015.A427), and the Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany (animal protocol number: G 14-1-040). All surgery was performed under deep isoflurane anesthesia.
Version history
- Received: April 7, 2017
- Accepted: September 14, 2017
- Accepted Manuscript published: September 15, 2017 (version 1)
- Accepted Manuscript updated: September 19, 2017 (version 2)
- Version of Record published: October 26, 2017 (version 3)
Copyright
© 2017, Schwalm 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.
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Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
eLife 6:e27602.
https://doi.org/10.7554/eLife.27602
Further reading
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Simultaneous measurements of neuronal activity and fMRI signals in the rat brain have shed new light on the origins of resting-state fMRI connectivity networks.
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Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.
