Biology subjects

Lenkei, Z.

Publications and source records attributed to Lenkei, Z..

4 recordsLinked to original sources

bioRxiv2025

Robust functional ultrasound imaging in the awake and behaving brain: a systematic framework for motion artifact removal

Functional ultrasound imaging (fUSI) is a promising tool for studying brain activity in awake and behaving animals, offering insights into neural dynamics that are more naturalistic than those obtained under anesthesia. However, motion artifacts pose a significant challenge, introducing biases that can compromise the integrity of the data. This study provides a comprehensive evaluation and benchmarking of strategies for detecting and removing motion artifacts in transcranial fUSI acquisitions of awake mice. We evaluated 792 denoising strategies across four datasets, focusing on clutter filtering, scrubbing, frequency filtering, and confound regression methods. Our findings highlight the superior performance of adaptive clutter filtering and aCompCor confound regression in mitigating motion artifacts while preserving functional connectivity patterns. We also demonstrate that high-pass filtering is generally more effective than band-pass filtering in the presence of motion artifacts. Additionally, we show that with effective clutter filtering, scrubbing may become optional, which is particularly beneficial for experimental designs where motion correlates with conditions of interest. Based on these insights, we propose four optimized denoising paradigms tailored to different experimental constraints, providing practical recommendations for enhancing the reliability and reproducibility of fUSI data. Our findings challenge current practices in the field and have immediate practical implications for existing fUSI analysis workflows, paving the way for more sophisticated applications of fUSI in studying complex brain functions and dysfunctions in awake experimental paradigms.

neuroscience↗

bioRxiv2023

The recycling endosome biogenesis machinery coordinates BACE1 endosomal sorting and amyloid-Beta production

Alzheimers disease (AD) is the most common form of dementia worldwide. One of ADs main pathological hallmarks is the cerebral plaque deposits of {beta}-amyloid (A{beta}). A{beta} is generated through sequential enzymatic cleavage of the amyloid precursor protein (APP). The {beta}-secretase or {beta}-site APP-cleaving enzyme 1 (BACE1) initiates this cleavage and is thus key to regulate A{beta} formation. Both APP and BACE1 transit through the endolysosomal system but the exact nature of the compartment(s) where APP cleavage occurs as well as the molecular mechanisms that govern their endosomal sorting remain poorly known. Here we show that RAB11 not only regulates BACE1 transport from early/sorting endosomes (EEs/SEs) and drives the exocytosis of BACE1-containing recycling carriers. Moreover, recycling endosome-associated KIF13A, as well as its closely related homolog KIF13B, which are known RAB11 effectors involved in the biogenesis of recycling endosome (RE) from EEs/SEs, also participate in BACE1 endosomal sorting. Importantly, depletion of KIF13A or KIF13B leads to an increase in A{beta} generation. Depletion of the BLOC-1 complex, previously described as an essential partner for KIF13A-dependent RE biogenesis, also induces increased amount of A{beta}. Altogether, our findings support a model where the EEs/SEs represent a major organelle for A{beta} formation and identify the recycling endosome biogenesis machinery as a master coordinator of BACE1 endosomal sorting and transport.

cell biology↗

bioRxiv2021

Microglia control cerebral blood flow and neurovascular coupling via P2Y12R-mediated actions

Microglia, the main immunocompetent cells of the brain regulate neuronal function in health and disease, but their contribution to cerebral blood flow (CBF) remained elusive. Here we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. We show that microglia establish direct purinergic contacts with cells in the neurovascular unit that shape cerebral perfusion in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in the barrel cortex after whisker stimulation. We also reveal that hypercapnia, which is associated with acidification, induces microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Furthermore, the absence or dysfunction of microglia markedly impairs adaptation to hypoperfusion via P2Y12R after transient unilateral common carotid artery occlusion, which is also influenced by CX3CR1-mediated actions. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation with broad implications for common neurological diseases.

neuroscience↗

bioRxiv2018

Actomyosin-mediated nanostructural remodeling of the presynaptic vesicle pool by cannabinoids induces long-term depression

Endo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release. However, the molecular mechanisms underlying the widely expressed endocannabinoid-mediated long-term depression (eCB-LTD), are poorly understood. Here, we reveal that eCB-LTD depends on the contractile properties of the pre-synaptic actomyosin cytoskeleton. Preventing this contractility, both directly by inhibiting non-muscle myosin II NMII ATPase and indirectly by inhibiting the upstream Rho-associated kinase ROCK, abolished long-term, but not short-term forms of cannabinoid-induced functional plasticity in both inhibitory hippocampal and excitatory cortico-striatal synapses. Furthermore, using 3D superresolution microscopy, we find an actomyosin contractility-dependent redistribution of synaptic vesicle pools within the presynaptic compartment following cannabinoid receptor activation, leading to vesicle clustering and depletion from the pre-synaptic active zone. These results suggest that cannabinoid-induced functional plasticity is mediated by a nanoscale structural reorganization of the presynaptic compartment produced by actomyosin contraction. By introducing the contractile NMII as an important actin binding/structuring protein in the dynamic regulation of synaptic function, our results open new perspectives in the understanding of mechanisms of synaptic and cognitive function, marijuana intoxication and psychiatric pathogenesis.

neuroscience↗