Other factors known to locally influence 5-HT neurotransmission are neurosteroids (eg, progesterone in the LEE011 order hypothalamus),166 lipids,167 and neurotrophic factors (eg, BDNF in the hippocampus).168 Although not exhaustive, most all of the reciprocal interactions exemplified above involve

specialized receptors. Concluding remarks It is conceivable that the list of molecular factors that act in 5-HT circuitries is still incomplete. The discovery of TPOH2 is less Inhibitors,research,lifescience,medical than 7 years old. Intriguingly, a very recent study in double (TPOH1/TPOH2) knockout mice mentioned a residual 5-HT synthesis, suggesting additional 5-HT synthetic pathway(s).169 Further, it can reasonably be assumed that 5-HT receptor subtypes resulting from postranslational editing or alternative splicing

mRNA are not restricted to 5-HT2C, 5-HT3, 5-HT4, and 5-HT7 Inhibitors,research,lifescience,medical receptor families. There is also a growing list of proteins playing a role in the regulation of SERT and 5HT receptor activity. Beyond the diversity of 5-HT receptor subtypes, their crosstalk modalities, and their local ability for adaptation, volume transmission demonstrated in several brain regions adds to the complexity of the serotonergic circuitries. Such complexity may explain Inhibitors,research,lifescience,medical why small subpopulations of cell bodies sending axons throughout the entire brain may produce such a large spectrum of effects in brain functions. Molecular and cellular studies in laboratory animal models (mutant mice, Caenorhabditis elegans, cell lines) and postmortem human brain have enabled us to explore the serotonergic Inhibitors,research,lifescience,medical system and will certainly continue to do so. Undoubtedly, improvement of the specificity and spatiotemporal resolution of in vivo imaging modalities coupled or not to pharmacological manipulations will also significantly contribute to a better knowledge of 5-HT circuitries, specifically in the living human brain. As already mentioned, human brain structures associated with emotional processing, attention, and some other cognitive functions, are

currently being investigated Inhibitors,research,lifescience,medical by MRI. TEP modalities allow the visualization of receptors including 5-HT receptors. A next step in functional neuroimaging will be hybrid-scanner systems that combine both technologies.170 Finally, our reviewing on brain serotonergic circuitries has not taken into account the next level of complexity, ie, the fact that the role of other neurotransmitters tuclazepam is not limited to the modulation of 5-HT neuron activity. Appendix – glossary Autoreceptors/heteroreceptors Autoreceptors are membrane receptors expressed by neurons that synthesize the neurotransmitter binding to these receptors, eg, 5-HT1A or 5-HT1B localized on 5-HT neuronal elements. In contrast, heteroreceptors are membrane receptors born by neurons that do not produce the corresponding neurotransmitter, eg, alpha2adrenoceptors on 5-HT neuronal elements.