Electrochemical serotonin microsensors for stable long-term measurement in real time
Dysregulation of serotonin plays a role in many psychiatric disorders, including severe depression and anxiety. In the journal Angewandte Chemie,
a research team has now introduced an implantable, electrochemical
microsensor that makes it possible to study serotonin dynamics in the
brain in real time. In contrast to previous sensors, these are not
deactivated by deposition of serotonin oxidation products because the
measurement occurs without current flow.

© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Serotonin, also known as the “happiness hormone”, is one of our most
important neurotransmitters, regulating many processes in our brain,
especially our feelings, but also appetite, memory, and sleep. A better
understanding of these processes on a molecular level could improve the
diagnosis and treatment of mental illnesses. Previous electrochemical
methods worked with a microelectrode, on which serotonin is directly
oxidized and the resulting current is measured. However, the resulting
oxidation products polymerize, adhere to the electrode surface
(fouling), and rapidly deactivate the sensor (about 90 % signal loss
within 30 minutes).
A team led by Ying Jiang and Lanqun Mao at Beijing Normal University
and the Chinese Academy of Sciences (Beijing, China) has now developed a
serotonin sensor that provides extremely stable signals, even during
long-term experiments, because almost no fouling due to serotonin
oligomers occurs. The method is based on galvanic redox potentiometry
(GRP), which is a zero-current technique.
The core of the sensor is a tiny bipolar electrode, which can
simplistically be described as a rod with one end protruding into the
liquid being measured while the other is in an electrolyte solution with
electrochemical properties that are precisely adjusted to the analyte
molecule. An electrical contact is established exclusively through the
electrolyte solution. At one end of the electrode, an electrochemical
equilibrium is established between electrolyte ions in various charge
states (in this case: IrCl62−/IrCl63−),
at the other end, there is an equilibrium between serotonin and its
oxidized form. By using a device to measure the voltage, it is possible
to measure the spontaneously established potential difference relative
to a reference electrode. This difference is dependent on the serotonin
concentration. Because only the voltage is measured and no current
flows, there is almost no deposition of oligomeric serotonin products.
Quantitative measurements are possible over a broad range of
concentrations and over a long period of time.
Sensors implanted into the brains of guinea pigs were able to follow
the release of serotonin after stimulation with potassium ions in real
time. The team made one interesting observation after administering
Escitalopram, a serotonin reuptake inhibitor often prescribed to treat
severe depression and anxiety disorders. Its activity seems to depend
more strongly on slowing the uptake process than on modulation of the
extracellular serotonin concentration. This insight could be important
for the treatment of psychiatric disorders.
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About the Author
Dr. Lanqun Mao is a
Professor of Chemistry at Beijing Normal University. He has been working
on the interface of electroanalytical chemistry and brain sciences for
over 25 years, focusing on developing electrochemical approaches to
understanding brain chemistry in single vesicles, single cells, brain
slices, and ultimately a living brain.
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