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          Institute: MPI für Neurobiologie     Collection: Systems and Computational Neurobiology     Display Documents

ID: 442933.0, MPI für Neurobiologie / Systems and Computational Neurobiology
An in vivo biosensor for neurotransmitter release and in situ receptor activity
Authors:Nguyen, Q. T.; Schroeder, L. F.; Mank, M.; Muller, A.; Taylor, P.; Griesbeck, O.; Kleinfeld, D.
Date of Publication (YYYY-MM-DD):2009-12-13
Title of Journal:Nature Neuroscience
Journal Abbrev.:Nat. Neurosci.
Volume:13 [2010]
Issue / Number:1
Start Page:127
End Page:132
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Tools from molecular biology, combined with in vivo optical imaging techniques, provide new mechanisms for noninvasively observing brain processes. Current approaches primarily probe cell-based variables, such as cytosolic calcium or membrane potential, but not cell-to-cell signaling. We devised cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) to address this challenge and monitor in situ neurotransmitter receptor activation. CNiFERs are cultured cells that are engineered to express a chosen metabotropic receptor, use the G(q) protein-coupled receptor cascade to transform receptor activity into a rise in cytosolic [Ca2+] and report [Ca2+] with a genetically encoded fluorescent Ca2+ sensor. The initial realization of CNiFERs detected acetylcholine release via activation of M1 muscarinic receptors. We used chronic implantation of M1-CNiFERs in frontal cortex of the adult rat to elucidate the muscarinic action of the atypical neuroleptics clozapine and olanzapine. We found that these drugs potently inhibited in situ muscarinic receptor activity.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Systems and Computational Neurobiology (Borst)/Cellular Dynamics (Griesbeck)
External Affiliations:[Nguyen, Quoc-Thang; Muller, Arnaud; Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.; [Schroeder, Lee F.] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92093 USA.; [Schroeder, Lee F.; Kleinfeld, David] Univ Calif San Diego, Grad Program Neurosci, La Jolla, CA 92093 USA.; [Taylor, Palmer] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.; [Kleinfeld, David] Univ Calif San Diego, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
Identifiers:ISI:000273056300023 [ID No:1]
ISSN:1097-6256 [ID No:2]
DOI:10.1038/nn.2469 [online 2009]
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