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Nat Neurosci. 2010 Jan;13(1):127-132. doi: 10.1038/nn.2469. Epub 2009 Dec 13.

An in vivo biosensor for neurotransmitter release and in situ receptor activity.

Author information

1
Physics Department, UCSD, La Jolla, CA.
2
Medical Scientist Training Program, UCSD, La Jolla, CA.
3
Graduate Program in Neurosciences, UCSD, La Jolla, CA.
4
Max-Planck Institut für Neurobiologie, Martinsried, Germany.
5
Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, La Jolla, CA.
6
Center for Neural Circuits and Behavior, UCSD, La Jolla, CA.
#
Contributed equally

Abstract

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 [Ca(2+)] and report [Ca(2+)] with a genetically encoded fluorescent Ca(2+) 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.

PMID:
20010818
PMCID:
PMC3992257
DOI:
10.1038/nn.2469
[Indexed for MEDLINE]
Free PMC Article

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