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Wednesday, December 07, 2011


Advancing neurochemical monitoring

Paul A Garris

Two new approaches to neurochemical monitorinign vivo—an

improved real-time microsensor and genetically engineered cells that

sense neurotransmitter levels—address the critical issue of brain

reactivity to implanted devices.

Identifying the neural basis of behavior

is a core focus of neuroscience. One

prominent methodology in this pursuit

is monitoring the neurotransmitters that

underlie communication between neu -

rons. Although technical improvements

have advanced neurochemical measu-re

ments to the real-time domain, one crit-i

cal limitation of present methods is the

highly invasive nature of implanting a

recording device and the subsequent re-ac

tion of brain tissue. Neuroin ammation

not only alters the sampled microenv-i

ronment, but also results in a di usion

barrier that encapsulates the probe and

therefore restricts access to released ne-u

rotransmitters. Taking radically di erent

strategies, two new approaches address

this key hurdle for achieving the longstanding

goal of chronic, real-time neurochemical

monitoring. In this issue of

Nature Methods, Clark et al.1 describe a

microelectrode that retains the capability

for subsecond dopamine measurementins

vivo for months. In Nature Neuroscience ,

Nguyen et al.2 report implantable genet-i

cally engineered cells for electrode-free

acetylcholine sensing.

Microdialysis3 and voltammetry4 have

dominated the modern era of neurochem- i

cal monitoring in vivo. With exquisite sensitivity

and selectivity by virtue of removing

brain analytes for ex vivo determination,

microdialysis is better suited for measu-r

ing basal neurotransmitter levels. By using

electrochemistry at the probe tip foirn situ

detection, the superior temporal resolution

of voltammetry is more appropriate

for capturing faster chemical signals.

Recent advances in voltammetry have

overcome the historical criticisms of

poor sensitivity and chemical speci city.

Indeed, by providing nanomolar

and subsecond measurements and a

chemical signature in the form of a vo-l

tammogram, fast-scan cyclic voltammetry

(FSCV) has met the demanding analytica l

criteria for monitoring phasic dopamine

Paul A. Garris is in the Department of Biological Science, Illinois State University, Normal, Illinois, USA.


© 2010 Nature America, Inc. All rights reserved.

nature methods
VOL.7 NO.2

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electrophysiologically. Optical imaging

techniques have also been recently used

for biosensing, using implantable cells

containing organic dyes for imaging Ca2+

in vivo11 and using neurotransmittersensitive

fluorescent proteins expressed

in cultured neurons12.

Nguyen et al.2 make use of these recent

advances in biosensing to develop electrode-

free, noninvasive methodology

for monitoring acetylcholine. In their

cell-based reporters, called CNiFERsa

clever twist of both the moniker and

the approach of the original ‘sniffer

pipette’detection is also based on

cholinergic receptors, in this case a

metabotropic receptor. CNiFERs are an

immortal cell line genetically engineered

to express a fluorescent Ca2+ protein sensor

and the M1 muscarinic receptor (Fig.

1b). Binding of acetylcholine initiates a

biochemical cascade involving a G protein,

phosopholipase C and the second

messenger inositol trisphosphate, ultimately

leading to increased intracellular

Ca2+ levels and altered fluorescence.

When chronically implanted in the rat

cortex and monitored by two-photon

laser-scanning microscopy, CNiFERs

robustly respond to basal and electrically

evoked levels of acetylcholine for up to six

days2. Suggestive of a physiological role,

measured signals temporally coincided