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.