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- W1551554098 abstract "From moment to moment, dynamic patterns of neurotransmitter release and surface receptor activity determine the function of the central nervous system. Fundamental to neuroscience is the ability to measure these patterns. However, the tools to make these measurements at a physiologically relevant temporal and spatial resolution are largely unavailable. Recent advances in genetically encoded optical biosensors have begun to allow direct visualization of molecular events previously only indirectly inferable. The aim of the work presented in this dissertation is to develop and characterize a novel in vivo cellular biosensor that takes advantage of current optical biosensor technology as well as standard cell-based assays used in high-throughput screening by the pharmaceutical industry. The biosensors are named Cell-based Neurotransmitter Fluorescent Engineered Reporters (CNiFERs). In this initial realization, we express the M1 muscarinic acetylcholine receptor and the fluorescent Ca²⁺ indicator TN-XXL in cultured HEK293 cells. Activation of the M1 receptor by acetylcholine leads to an increase in HEK293 cytosolic Ca²⁺ then reported by TN-XXL. In vivo, M1-CNiFERs are implanted with control-CNiFERs: HEK293 cells expressing TN -XXL and the non-functional fluorescent protein mCherry, but not M1. M1- but not control-CNiFERs respond robustly, up to 40% signal change, to endogenous acetylcholine release evoked via electrical stimulation of Nucleus Basalis Magnocellularis (NBM). The response is a single peak initiated within 2 s with a half-maximal rise time as short as 1 s and a full width at half maximal amplitude of < 10 s. As expected for NBM stimulation, we observe an inverse correlation between M1-CNiFER response and electrocorticogram delta band power. The cholinergic nature of this response is further verified by enhancement with the acetylcholinesterase inhibitor physostigmine and suppression with the muscarinic antagonist atropine. The pharmaceutical industry has made such extensive use of the cell-based assay in part because of its modularity. By simply expressing a different receptor, CNiFERs can be built to detect the release of a large number of endogenous neurotransmitters and signaling molecules implicated in a wide variety of central nervous system functions" @default.
- W1551554098 created "2016-06-24" @default.
- W1551554098 creator A5049966497 @default.
- W1551554098 date "2009-01-01" @default.
- W1551554098 modified "2023-09-27" @default.
- W1551554098 title "An in vivo biosensor for neurotransmitter release and In situ receptor activity : acetylcholine and the M1 muscarinic receptor" @default.
- W1551554098 cites W1494500074 @default.
- W1551554098 cites W1512774816 @default.
- W1551554098 cites W1516658808 @default.
- W1551554098 cites W1557163873 @default.
- W1551554098 cites W1562398969 @default.
- W1551554098 cites W1596886387 @default.
- W1551554098 cites W1599216135 @default.
- W1551554098 cites W1647678806 @default.
- W1551554098 cites W1813932451 @default.
- W1551554098 cites W1818623226 @default.
- W1551554098 cites W1819535489 @default.
- W1551554098 cites W1854670164 @default.
- W1551554098 cites W1865166881 @default.
- W1551554098 cites W1874938414 @default.
- W1551554098 cites W18899968 @default.
- W1551554098 cites W1932235786 @default.
- W1551554098 cites W1967474964 @default.
- W1551554098 cites W1968960126 @default.
- W1551554098 cites W1972759599 @default.
- W1551554098 cites W1974530884 @default.
- W1551554098 cites W1977041705 @default.
- W1551554098 cites W1980819333 @default.
- W1551554098 cites W1984784421 @default.
- W1551554098 cites W1986609940 @default.
- W1551554098 cites W1990273208 @default.
- W1551554098 cites W1991574312 @default.
- W1551554098 cites W1993886090 @default.
- W1551554098 cites W1995621028 @default.
- W1551554098 cites W1998197993 @default.
- W1551554098 cites W1999508322 @default.
- W1551554098 cites W2002083376 @default.
- W1551554098 cites W2004713321 @default.
- W1551554098 cites W2010558759 @default.
- W1551554098 cites W2011406750 @default.
- W1551554098 cites W2011921884 @default.
- W1551554098 cites W2013132270 @default.
- W1551554098 cites W2020023795 @default.
- W1551554098 cites W2023283315 @default.
- W1551554098 cites W2024897089 @default.
- W1551554098 cites W2026382141 @default.
- W1551554098 cites W2026907517 @default.
- W1551554098 cites W2027009747 @default.
- W1551554098 cites W2027764322 @default.
- W1551554098 cites W2028127185 @default.
- W1551554098 cites W2028415754 @default.
- W1551554098 cites W2032698400 @default.
- W1551554098 cites W2033958927 @default.
- W1551554098 cites W2035187847 @default.
- W1551554098 cites W2035745394 @default.
- W1551554098 cites W2037200881 @default.
- W1551554098 cites W2038035800 @default.
- W1551554098 cites W2038300112 @default.
- W1551554098 cites W2039276784 @default.
- W1551554098 cites W2039975167 @default.
- W1551554098 cites W2040361910 @default.
- W1551554098 cites W2048507488 @default.
- W1551554098 cites W2050455764 @default.
- W1551554098 cites W2059182002 @default.
- W1551554098 cites W2060909855 @default.
- W1551554098 cites W2061464631 @default.
- W1551554098 cites W2061891949 @default.
- W1551554098 cites W2064306453 @default.
- W1551554098 cites W2065009632 @default.
- W1551554098 cites W2066482395 @default.
- W1551554098 cites W2068924803 @default.
- W1551554098 cites W2070110890 @default.
- W1551554098 cites W2072947781 @default.
- W1551554098 cites W2073189873 @default.
- W1551554098 cites W2074107495 @default.
- W1551554098 cites W2074698051 @default.
- W1551554098 cites W2080203764 @default.
- W1551554098 cites W2086310064 @default.
- W1551554098 cites W2091314916 @default.
- W1551554098 cites W2092554044 @default.
- W1551554098 cites W2092869045 @default.
- W1551554098 cites W2093545276 @default.
- W1551554098 cites W2093709619 @default.
- W1551554098 cites W2095649898 @default.
- W1551554098 cites W2096022141 @default.
- W1551554098 cites W2102733342 @default.
- W1551554098 cites W2113460545 @default.
- W1551554098 cites W2114689164 @default.
- W1551554098 cites W2133636515 @default.
- W1551554098 cites W2143152453 @default.
- W1551554098 cites W2144080252 @default.
- W1551554098 cites W2147607085 @default.
- W1551554098 cites W2152901500 @default.
- W1551554098 cites W2153762687 @default.
- W1551554098 cites W2155265451 @default.
- W1551554098 cites W2160356704 @default.
- W1551554098 cites W2161627797 @default.
- W1551554098 cites W2162997245 @default.
- W1551554098 cites W2166272307 @default.
- W1551554098 cites W2167460696 @default.