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Publications (3 of 3) Show all publications
Moulin, T. C., Petiz, L. L., Rayêe, D., Winne, J., Maia, R. G., Lima da Cruz, R. V., . . . Leão, R. N. (2019). Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus. Hippocampus, 29(8), 755-761
Open this publication in new window or tab >>Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus
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2019 (English)In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 29, no 8, p. 755-761Article in journal (Refereed) Published
Abstract [en]

Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

Keywords
long-term depression, long-term potentiation, optogenetics, synaptic plasticity, synaptic scaling
National Category
Biophysics Neurosciences
Identifiers
urn:nbn:se:uu:diva-380035 (URN)10.1002/hipo.23080 (DOI)000475815400008 ()30767318 (PubMedID)
Available from: 2019-03-22 Created: 2019-03-22 Last updated: 2019-08-16Bibliographically approved
Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L. & Leão, R. N. (2018). A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus. Frontiers in Molecular Neuroscience, 11, Article ID 312.
Open this publication in new window or tab >>A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus
2018 (English)In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 11, article id 312Article in journal (Refereed) Published
Abstract [en]

The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

Keywords
5-MeO-DMT, adult neurogenesis, patch clamp, psychedelics, dentate gyrus granule cells
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-364247 (URN)10.3389/fnmol.2018.00312 (DOI)000443650200001 ()30233313 (PubMedID)
Note

Correction in: FRONTIERS IN MOLECULAR NEUROSCIENCE, Volume: 12, Article Number: 79, DOI: 10.3389/fnmol.2019.00079

Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-04-24Bibliographically approved
Moulin, T., Rayee, D., Maia, R., Freitas, J., Lima, R., Petiz, L., . . . Amaral, O. (2018). Chronic in vivo optogenetic stimulation modulates Hebbian plasticity and spine density in the mouse hippocampus. biorxiv
Open this publication in new window or tab >>Chronic in vivo optogenetic stimulation modulates Hebbian plasticity and spine density in the mouse hippocampus
Show others...
2018 (English)In: biorxivArticle in journal (Other academic) Published
Abstract [en]

Continuous excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely-moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, and (b) lead to alterations in Hebbian plasticity. After 24 h of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density was reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also impaired the induction of LTP and facilitated that of LTD in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

Keywords
optogenetic, LTP
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-364406 (URN)10.1101/320507 (DOI)
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2019-01-23Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3845-7244

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