Biology subjects

Straehle, J.

Publications and source records attributed to Straehle, J..

4 recordsLinked to original sources

bioRxiv2026

Human cortical slices reveal pulse-number-dependent synaptic plasticity during theta-burst magnetic stimulation

Theta-burst transcranial magnetic stimulation is widely used to modulate human brain activity in clinical and experimental settings, yet how clinically relevant stimulation protocols engage synaptic plasticity in human cortical circuits remains poorly understood. Here, we combined controlled magnetic stimulation of viable adult human cortical slices with single-cell electrophysiology to determine whether pulse number constrains synaptic plasticity during intermittent theta-burst stimulation (iTBS). As a functional reference, 10 Hz repetitive magnetic stimulation delivered with 900 pulses robustly potentiated excitatory synaptic transmission in human cortical pyramidal neurons. Similarly, iTBS900 significantly potentiated AMPA receptor-mediated miniature excitatory postsynaptic currents. In contrast, the clinically established 600-pulse iTBS protocol failed to reliably induce detectable synaptic plasticity under otherwise identical stimulation conditions. Paired within-patient experiments confirmed distinct synaptic responses to iTBS600 and iTBS900 in the same human cortical tissue preparations. Together, these findings identify pulse number as an important determinant of theta-burst magnetic stimulation-induced synaptic plasticity in human cortical microcircuits and highlight stimulation dose as a relevant parameter for the design and refinement of therapeutic stimulation protocols.

neuroscience↗

bioRxiv2025

Efficient Prospective Electric Field-Informed Localization of Motor Cortical Targets of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a versatile non-invasive tool for brain mapping and neu-romodulation in both healthy individuals and patients. Effective TMS-based causal brain mapping relies on precise localization of cortical targets. Current state-of-the-art approaches use statistical methods to quantify the relationship between TMS-induced electric fields (E-fields) and motor evoked potential (MEP) amplitudes. However, this method typically relies on the random selection of coil configurations, which limits its efficacy. In this study, we present a novel optimization strategy for TMS-based motor mapping by prospectively selecting coil configurations based on their E-field characteristics using an iterative sampling algorithm called farthest point sampling (FPS). Through a combination of theoretical analysis, simulation and experimental validation including 10 healthy individuals, we systematically evaluated the performance of FPS against the random sampling approach. Our results demonstrate that FPS is twice as efficient as random sampling in reducing the number of trials required for estimating the motor map, while also being more robust across participants and less susceptible to noise. These findings highlight the potential of FPS to significantly enhance the efficiency of motor mapping, paving the way for the development of more effective TMS mapping algorithms.

neuroscience↗

bioRxiv2023

Antiepileptic medication strengthens excitatory neurotransmission in pyramidal neurons of the adult human neocortex

Homeostatic synaptic plasticity serves to maintain neuronal function within a dynamic range upon perturbations in network activity. While coordinated structural and functional changes at synaptic sites play a crucial role in adaptive processes, the specific regulatory mechanisms and biological relevance of homeostatic plasticity in the human brain warrant further investigation. In this study, we investigated the effects of neural network silencing, achieved through pharmacological inhibition of voltage-gated sodium channels or glutamatergic neurotransmission - common targets of antiepileptic medication - on functional and structural properties of murine and human cortical tissue. Using mouse entorhino-hippocampal tissue cultures, acute neocortical slices of adult mice, and human brain tissue, we characterize homeostatic synaptic plasticity across models, brain regions, and species. Our findings demonstrate local homeostatic synaptic plasticity in the adult human neocortex, highlighting the potential effects of antiepileptic medication in brain regions unaffected by the primary diseases, which might represent a mechanism for neuropsychiatric effects linked to these medications and increased seizure susceptibility upon discontinuation of antiepileptic medication.

neuroscience↗

bioRxiv2020

All-Trans Retinoic Acid induces synaptic plasticity in human cortical neurons

A defining feature of the brain is its ability to adapt structural and functional properties of synaptic contacts in an experience-dependent manner. In the human cortex direct experimental evidence for synaptic plasticity is currently missing. Here, we probed plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid, which has been suggested as medication for the treatment of neuropsychiatric disorders, e.g., Alzheimers disease. Our experiments demonstrate coordinated structural and functional changes of excitatory synapses of superficial (layer 2/3) pyramidal neurons in the presence of all-trans retinoic acid. This synaptic adaptation is accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and requires mRNA-translation. We conclude that all-trans retinoic acid is a potent mediator of synaptic plasticity in the adult human cortex.

neuroscience↗