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The behavioural impact of serotonin

The brain transmits information to the body through electrochemical signals that are fired following the binding of specific molecules onto neuronal synapses. The RAPHE study developed a transgenic mouse model that allowed the identification and monitoring of serotonergic neurons in the brain.
The behavioural impact of serotonin
Serotonin, or 5-Hydroxytryptamine (5-HT), is a neurotransmitter molecule implicated in a variety of behavioural, cognitive and emotional processes. The targeting of 5-HT with drugs constitutes a common treatment for some major psychiatric and neurological diseases.

Most of the brain 5-HT innervation originates in a specific neuronal network located in the brainstem called the raphe nuclei (RN). Knowledge about 5-HT function is limited by technical difficulties such as neurochemical identity of the recorded cells.

In order to study the cell features of serotonergic neurons, the EU-funded RAPHE project used genetic manipulation to enable the anatomical localisation of these neurons. A Cre recombinase enzyme-dependent adeno-associated virus vector was used to genetically modify mice selectively expressing Cre recombinase in serotonin transporter-expressing (SERT) neurons. The ion channel channelrhodopsin (ChR2) of raphe nucleus 5-HT neurons in these mice were photo stimulated to generate action potentials that were recorded. As a result, ChR2 expression was evident in all neurons where serotonin bound to SERT.

In order to study the behavioural effects in these animals, 5-HT neurons were implanted with a fibre-optic cannula for photostimulation and electroencephalography (EEG) electrodes for monitoring. Scientists found that when the animals were in slow-wave sleep, a short wave of photostimulation was sufficient to awaken them, thus verifying the functionality of this transgenic mouse model.

The RAPHE animal model of 5-HT localisation constitutes an important tool for studying the neurochemical and anatomical identity of 5-HT neurons. In essence, this will provide information on the behavioural effect of serotonin.

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