Spacing theta-burst stimulation enhances synaptic potentiation in the vulnerable prefrontal cortex
- 1University of Toronto
Abstract
Neuromodulation with intermittent theta-burst stimulation (iTBS) is a clinical treatment for major depression. One postulated mechanism of iTBS is to strengthen the synaptic connections which activate the prefrontal cortex to regulate mood. With ex vivo electrical stimulation and neuronal calcium imaging, we demonstrate that a common, clinical iTBS pattern (600-stimuli, ~3-minutes) reliably strengthens the synaptic recruitment of the adult mouse prefrontal cortex. This synaptic potentiation, however, becomes less reliable in the depressive-like mouse model of prolonged social isolation. To better understand this change, we examine the impact of social isolation on the complex pattern of calcium elevation during clinical iTBS. In social isolation, the calcium peaks rise more prominently, but the induction peak no longer predicts the synaptic potentiation outcome. To better regulate calcium dynamics during induction, we test a paradigm with fewer iTBS episodes, separated by longer intervals. This spaced iTBS (90-stimuli, ~10-minutes) in the adult prefrontal cortex limits calcium elevation during induction and yields reliable long-term potentiation (LTP) following either juvenile- or adult-onset social isolation. This research illustrates new strategies to interrogate and to enhance synaptic plasticity in the vulnerable prefrontal cortex.
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BibTeX
@misc{zolis2026spacing,
title = {{Spacing theta-burst stimulation enhances synaptic potentiation in the vulnerable prefrontal cortex}},
author = {A. Zolis and A. H.-Y. Hsieh and S. Venkatesan and R. Ingram and J. Georgiou and C. Zrenner and G. L. Collingridge and T. K. Rajji and E. K. Lambe},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.746330},
url = {https://www.biorxiv.org/content/10.64898/2026.08.27.746330v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Spacing theta-burst stimulation enhances synaptic potentiation in the vulnerable prefrontal cortex
AU - A. Zolis
AU - A. H.-Y. Hsieh
AU - S. Venkatesan
AU - R. Ingram
AU - J. Georgiou
AU - C. Zrenner
AU - G. L. Collingridge
AU - T. K. Rajji
AU - E. K. Lambe
PY - 2026
DA - 2026/08/27
PB - bioRxiv
DO - 10.64898/2026.08.27.746330
UR - https://www.biorxiv.org/content/10.64898/2026.08.27.746330v1
AB - Neuromodulation with intermittent theta-burst stimulation (iTBS) is a clinical treatment for major depression. One postulated mechanism of iTBS is to strengthen the synaptic connections which activate the prefrontal cortex to regulate mood. With ex vivo electrical stimulation and neuronal calcium imaging, we demonstrate that a common, clinical iTBS pattern (600-stimuli, ~3-minutes) reliably strengthens the synaptic recruitment of the adult mouse prefrontal cortex. This synaptic potentiation, however, becomes less reliable in the depressive-like mouse model of prolonged social isolation. To better understand this change, we examine the impact of social isolation on the complex pattern of calcium elevation during clinical iTBS. In social isolation, the calcium peaks rise more prominently, but the induction peak no longer predicts the synaptic potentiation outcome. To better regulate calcium dynamics during induction, we test a paradigm with fewer iTBS episodes, separated by longer intervals. This spaced iTBS (90-stimuli, ~10-minutes) in the adult prefrontal cortex limits calcium elevation during induction and yields reliable long-term potentiation (LTP) following either juvenile- or adult-onset social isolation. This research illustrates new strategies to interrogate and to enhance synaptic plasticity in the vulnerable prefrontal cortex.
ER -