Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

Background: Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learni...

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Autores principales:	Mahima Sharma, Forouzan Farahani, Marom Bikson, Lucas C. Parra
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Transcranial direct current stimulation Direct current stimulation Synaptic plasticity LTP TBS-LTP Spaced learning Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/fb96eae54bc145de893e6bf643bd73a1
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spelling	oai:doaj.org-article:fb96eae54bc145de893e6bf643bd73a12021-11-12T04:29:45ZWeak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning1935-861X10.1016/j.brs.2021.10.552https://doaj.org/article/fb96eae54bc145de893e6bf643bd73a12022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1935861X21007981https://doaj.org/toc/1935-861XBackground: Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning. Hypothesis: We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities. Methods: We leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices. Results: As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied). Conclusions: Weak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.Mahima SharmaForouzan FarahaniMarom BiksonLucas C. ParraElsevierarticleTranscranial direct current stimulationDirect current stimulationSynaptic plasticityLTPTBS-LTPSpaced learningNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Stimulation, Vol 15, Iss 1, Pp 57-62 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Transcranial direct current stimulation Direct current stimulation Synaptic plasticity LTP TBS-LTP Spaced learning Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Transcranial direct current stimulation Direct current stimulation Synaptic plasticity LTP TBS-LTP Spaced learning Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Mahima Sharma Forouzan Farahani Marom Bikson Lucas C. Parra Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
description	Background: Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning. Hypothesis: We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities. Methods: We leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices. Results: As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied). Conclusions: Weak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.
format	article
author	Mahima Sharma Forouzan Farahani Marom Bikson Lucas C. Parra
author_facet	Mahima Sharma Forouzan Farahani Marom Bikson Lucas C. Parra
author_sort	Mahima Sharma
title	Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
title_short	Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
title_full	Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
title_fullStr	Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
title_full_unstemmed	Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
title_sort	weak dcs causes a relatively strong cumulative boost of synaptic plasticity with spaced learning
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/fb96eae54bc145de893e6bf643bd73a1
work_keys_str_mv	AT mahimasharma weakdcscausesarelativelystrongcumulativeboostofsynapticplasticitywithspacedlearning AT forouzanfarahani weakdcscausesarelativelystrongcumulativeboostofsynapticplasticitywithspacedlearning AT marombikson weakdcscausesarelativelystrongcumulativeboostofsynapticplasticitywithspacedlearning AT lucascparra weakdcscausesarelativelystrongcumulativeboostofsynapticplasticitywithspacedlearning
_version_	1718431326123589632

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

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