Biology subjects

Elgueta, C.

Publications and source records attributed to Elgueta, C..

3 recordsLinked to original sources

bioRxiv2026

Daily repetitive magnetic stimulation induces microglia-dependent homeostatic synaptic remodeling

Therapeutic repetitive transcranial magnetic stimulation (rTMS) is delivered across repeated sessions to induce durable network-level adaptations, yet the cellular mechanisms governing these cumulative effects remain poorly understood. Using mouse organotypic brain cultures, we show that repeated daily intermittent theta burst stimulation with 900 pulses (iTBS900; 10 stimulation sessions over 2 weeks) induces a microglia-dependent adaptive synaptic response in pyramidal neurons. This response is characterized by reduced AMPAR-mediated miniature excitatory postsynaptic current (mEPSC) frequency and decreased dendritic spine density, consistent with adaptive remodeling of excitatory synaptic connectivity. Microglial depletion abolished this homeostatic response and instead resulted in increased synaptic strength and elevated spine density following repeated stimulation. Repeated daily iTBS900 also enhanced microglial uptake and degradative capacity while altering baseline and injury-induced microglial motility, indicating stimulation-dependent changes in microglial surveillance and effector functions. Together, these findings identify microglia as critical mediators of the homeostatic structural and functional adaptations induced by multi-session rTMS.

neuroscience↗

bioRxiv2026

GABAergic inhibition differentially gates recruitment of dentate gyrus interneurons by lateral entorhinal cortex inputs.

By keeping its activity low even when strongly stimulated, the dentate gyrus (DG) serves as the main entry point to the hippocampal circuit and helps separate different patterns of incoming information. However, the mechanisms supporting this low-level activity remain unclear. Here, we used in vitro patch-clamp recordings, two-photon calcium imaging, and optogenetics in hippocampal slices from adult mice to understand how local GABAergic interneurons control lateral entorhinal cortex (LEC) input-mediated drive in the DG. Under control conditions, LEC inputs rarely elicited granule cell (GC) firing because GABAA receptor-mediated inhibition strongly restrained GC excitability. Whole-cell patch clamp recordings of DG interneurons revealed that LEC activation prevalently recruited fast-spiking parvalbumin-expressing and molecular layer interneurons, while most dendrite-targeting interneuron types responded only weakly to LEC input and fired action potentials only after feedback excitation from GCs was enhanced by pharmacological block of GABAA-receptors. Optogenetic inhibition of defined interneuron populations showed that silencing dendrite-targeting interneurons caused a larger increase in GC population spiking than silencing perisomatic-targeting interneurons, suggesting that both molecular layer and feedback-recruited interneurons have a prevalent role in controlling DG recruitment after an increase in LEC drive. In summary, our data indicate that GABAergic inhibition engages distinct DG interneuron types in feedforward and feedback circuits to tightly gate entorhinal inputs. By maintaining sparse GC firing, this dynamic inhibitory gating supports the role of the dentate gyrus in the hippocampal pattern-separation process.

neuroscience↗

bioRxiv2020

Optogenetic low-frequency stimulation of dentate granule cells prevents seizure generation in experimental epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults and is typically associated with hippocampal sclerosis and drug-resistant seizures. As an alternative to curative epilepsy surgery, brain stimulation evolves as a promising approach for seizure-interference. However, particularly in MTLE with severe hippocampal sclerosis, current stimulation protocols are often not effective. Here, we show that optogenetic low-frequency stimulation (oLFS) of entorhinal afferents exhibits unprecedented anti-ictogenic effects in chronically epileptic mice. Photostimulation at 1 Hz resulted in an almost complete suppression of focal seizures, independent of the degree of hippocampal sclerosis. Furthermore, by performing oLFS for 30 min before a pro-convulsive stimulus, seizure generalization was successfully prevented. Finally, acute slice experiments revealed a decreased excitability upon oLFS, which may partially explain the observed anti-epileptic effects. Taken together, our results suggest that oLFS of entorhinal afferents constitutes a promising approach for seizure control in MTLE.

physiology↗