Inducing a long-term potentiation in the dentate gyrus is sufficient to produce rapid antidepressant-like effects.
Mol Psychiatry. 2017-05-09; 23(3): 587-596
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1. Mol Psychiatry. 2018 Mar;23(3):587-596. doi: 10.1038/mp.2017.94. Epub 2017 May 9.
Inducing a long-term potentiation in the dentate gyrus is sufficient to produce
rapid antidepressant-like effects.
Kanzari A(1)(2), Bourcier-Lucas C(3), Freyssin A(1), Abrous DN(3), Haddjeri N(1),
(1)INSERM and Université Claude Bernard Lyon 1, Institut Cellule Souche et
Cerveau U846, Lyon, France.
(2)Department of Biology, Université de Tunis El Manar, Tunis, Tunisia.
(3)INSERM and Université de Bordeaux, Neurocentre Magendie U1215, Bordeaux,
Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant
(AD) effect would reside in processes of synaptic reinforcement occurring within
the dentate gyrus (DG) of the hippocampus independently from neurogenesis.
However, to date no relationship has been established between an increased DG
synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this
study shows for the first time that inducing a long-term potentiation (LTP)
within the DG by stimulating the perforant pathway (PP) is sufficient to induce
such effects. Thus, Sprague-Dawley rats having undergone a successful LTP
displayed a significant reduction of immobility when passed acutely 3 days
thereafter in the forced swimming test (FST). Further, in a longitudinal paradigm
using the pseudo-depressed Wistar-Kyoto rat strain, LTP elicited a decrease of
FST immobility after only 2 days, whereas the AD desipramine was not effective
before 16 days. In both models, the influence of LTP was transient, as it was no
more observed after 8-9 days. No effects were observed on the locomotor activity
or on anxiety-related behavior. Theta-burst stimulation of a brain region
anatomically adjacent to the PP remained ineffective in the FST. Immunoreactivity
of DG cells for phosphorylated histone H3 and doublecortin were not modified
three days after LTP, indicating a lack of effect on both cell proliferation and
neurogenesis. Finally, depleting brain serotonin contents reduced the success
rate of LTP but did not affect its subsequent AD-like effects. These results
confirm the ‘plastic DG’ theory of rapid AD efficacy. Beyond, they point out
stimulations of the entorhinal cortex, from which the PP originates, as putative
new approaches in AD research.