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Article

Feasibility of Canine Adenovirus Type 2 (CAV2) Based Vector for the Locus Coeruleus Optogenetic Activation in Non-Transgenic Rats: Implications for Functional Studies

1
Department of Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, 72076 Tübingen, Germany
2
Division of Imaging Science and Biomedical Engineering, University of Manchester, Manchester M13 9PT, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Anja Teschemacher
Brain Sci. 2022, 12(7), 904; https://doi.org/10.3390/brainsci12070904
Received: 24 May 2022 / Revised: 3 July 2022 / Accepted: 8 July 2022 / Published: 10 July 2022
The locus coeruleus norepinephrine (LC-NE) system modulates many visceral and cognitive functions, while LC-NE dysfunction leads to neurological and neurodegenerative conditions such as sleep disorders, depression, ADHD, or Alzheimer’s disease. Innovative viral-vector and gene-engineering technology combined with the availability of cell-specific promoters enabled regional targeting and selective control over phenotypically specific populations of neurons. We transduced the LC-NE neurons in adult male rats by delivering the canine adenovirus type 2-based vector carrying the NE-specific promoter PRSx8 and a light-sensitive channelrhodopsin-2 receptor (ChR2) directly in the LC or retrogradely from the LC targets. The highest ChR2 expression level was achieved when the virus was delivered medially to the trigeminal pathway and ~100 μm lateral to the LC. The injections close or directly in the LC compromised the tissue integrity and NE cell phenotype. Retrograde labeling was more optimal given the transduction of projection-selective subpopulations. Our results highlight a limited inference of ChR2 expression from representative cases to the entire population of targeted cells. The actual fraction of manipulated neurons appears most essential for an adequate interpretation of the study outcome. The actual fraction of manipulated neurons appears most essential for an adequate interpretation of the study outcome. Thus, besides the cell-type specificity and the transduction efficiency, the between-subject variability in the proportion of the remaining viral-transduced targeted cell population must be considered in any functional connectivity study. View Full-Text
Keywords: locus coeruleus; optogenetics; channel-rhodopsin; immunohistochemistry; non-transgenic rat; CAV2 virus; norepinephrine; retrograde tracing; PRSx8 promoter locus coeruleus; optogenetics; channel-rhodopsin; immunohistochemistry; non-transgenic rat; CAV2 virus; norepinephrine; retrograde tracing; PRSx8 promoter
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MDPI and ACS Style

Kabanova, A.; Cavani, E.; Logothetis, N.K.; Eschenko, O. Feasibility of Canine Adenovirus Type 2 (CAV2) Based Vector for the Locus Coeruleus Optogenetic Activation in Non-Transgenic Rats: Implications for Functional Studies. Brain Sci. 2022, 12, 904. https://doi.org/10.3390/brainsci12070904

AMA Style

Kabanova A, Cavani E, Logothetis NK, Eschenko O. Feasibility of Canine Adenovirus Type 2 (CAV2) Based Vector for the Locus Coeruleus Optogenetic Activation in Non-Transgenic Rats: Implications for Functional Studies. Brain Sciences. 2022; 12(7):904. https://doi.org/10.3390/brainsci12070904

Chicago/Turabian Style

Kabanova, Anna, Elena Cavani, Nikos K. Logothetis, and Oxana Eschenko. 2022. "Feasibility of Canine Adenovirus Type 2 (CAV2) Based Vector for the Locus Coeruleus Optogenetic Activation in Non-Transgenic Rats: Implications for Functional Studies" Brain Sciences 12, no. 7: 904. https://doi.org/10.3390/brainsci12070904

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