Creation of the viral vectors for the inhibition of the serotonergic neurons using light sensitive proton pump
DOI:
https://doi.org/10.33910/2687-1270-2020-1-2-144-146Keywords:
serotonin, viral transfection, optogenetics, archaerhodopsin, rapheAbstract
Depression is the most frequently diagnosed psychiatric disease in Western countries. Although a variety of pharmacological treatments for this disorder are available, a significant proportion of patients is treatment-resistant and/or suffer from side effects. There is a growing need for a complex understanding of the underlying pathogenic mechanisms in the neural circuits and effort for developing novel therapies for the depression. The role of serotonin in depression and antidepressant treatment remains unclear despite decades of research. New optogenetic tools for manipulation of neuronal activity have enabled the investigation of the contribution of distinct neural circuit elements to the pathogenesis of depression. In this study, we used the specific lentiviral vectors for the inhibition of serotonergic neurons. The proton pump archaerhodopsin-3 (eArchT3.0) has been expressed in the serotonergic neurons under the control of tryptophan hydroxylase 2 promotor. Green light stimulation of eArchT3.0 expressing neurons led to a reduced percentage of c-Fos expressing cells among thоse neurons, which indicates a decrease in their activity.
References
Flavell, S. W., Greenberg, M. E. (2008) Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annual Review of Neuroscience, vol. 31, pp. 563–590. PMID: 18558867. DOI: 10.1146/annurev.neuro.31.060407.125631 (In English)
Gaynes, B. N. (2009) Identifying difficult-to-treat depression: Differential diagnosis, subtypes, and comorbidities. The Journal of Clinical Psychiatry, vol. 70, suppl. 6, pp. 10–15. PMID: 19922739. DOI: 10.4088/JCP.8133su1c.02 (In English)
Greer, P. L., Greenberg, M. E. (2008) From synapse to nucleus: Calcium-dependent gene transcription in the control of synapse development and function. Neuron, vol. 59, no. 6, pp. 846–860. PMID: 18817726. DOI: 10.1016/j. neuron.2008.09.002 (In English)
Krol, A., Lopez Huerta, V. G., Corey, T. E. C. et al. (2019) Two eARCHT3.0 lines for optogenetic silencing of dopaminergic and serotonergic neurons. Frontiers in Neural Circuits, vol. 13, article 4. PMID: 30774584. DOI: 10.3389/fncir.2019.00004 (In English)
Muir, J., Bagot, R. C. (2019) Optogenetics: Illuminating the neural circuits of depression. In: J. Quevedo, A. F. Carvalho, C. A. Zarate (eds.). Neurobiology of depression: Road to novel therapeutics. S. p.: Academic Press, pp. 147–157. DOI: 10.1016/B978-0-12-813333-0.00014-7 (In English)
Nishitani, N., Nagayasu, K., Asaoka, N. et al. (2019) Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats. Neuropsychopharmacology, vol. 44, no. 4, pp. 721–732. PMID: 30377380. DOI: 10.1038/s41386-018-0254-y (In English)
Post, R. J., Warden, M. R. (2018) Melancholy, anhedonia, apathy: The search for separable behaviors and neural circuits in depression. Current Opinion in Neurobiology, vol. 49, pp. 192–200. PMID: 29529482. DOI: 10.1016/j.conb.2018.02.018 (In English)
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