Biology subjects

Szigeti, K.

Publications and source records attributed to Szigeti, K..

5 recordsLinked to original sources

bioRxiv2026

Binary partitioning of human brain organization due to divergent human cytoskeletal evolution

CHRFAM7A is a biallelic uniquely human fusion gene present in 99.3% of humans. The direct and inverted alleles likely emerged independently in Africa and East Asia. We uncovered that the inverted allele regulates ULK4 expression through genetic epistasis. The increase in long to short ULK4 isoform ratio enhances -tubulin acetylation leading to microtubule (MT) cytoskeleton phenotypes (cell body: microtubule rich projections; neurite: de-bundling; growth cone: fanning with MT invasion). The MT cytoskeleton gain of function enhances neuronal arborization and functional connectivity in the human brain. Considering that the previously reported direct allele leads to actin cytoskeleton gain of function, we propose that CHRFAM7A alleles represent binary human genetic background through divergent evolution of the cytoskeleton. In the human brain the two alleles represent distinct brain organization: the direct allele enhances microstructure as measured by diffusion tensor imaging while the inverted allele increases functional connectivity with increased small world propensity. The two types of brain organization likely represent different susceptibility to neuropsychiatric disease and may underlie the allelic disease associations. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/725959v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@a84e75org.highwire.dtl.DTLVardef@1b712d9org.highwire.dtl.DTLVardef@367c01org.highwire.dtl.DTLVardef@1074dc4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Cholinergic--dopaminergic interplay underlies prediction error broadcasting

Neuromodulatory systems, notably basal forebrain cholinergic and midbrain dopaminergic pathways, critically influence reinforcement learning 1-3. However, whether and how they cooperate or compete to jointly control associative learning functions remains unresolved. Here we demonstrate that basal forebrain cholinergic and midbrain dopaminergic projection systems form a coordinated and cross-regulating architecture for encoding prediction errors. Using dual-cell-type optogenetic tagging and real-time neurotransmitter measurements in mice performing a psychometric operant learning task, we simultaneously monitored cholinergic and dopaminergic activity during learning. Dopamine and acetylcholine jointly encoded reward prediction errors synergistically following reward and reward-predicting stimuli. In contrast, aversive outcomes elicited opposite responses in cholinergic neurons and approximately half of dopaminergic neurons. Activity in these two populations exhibited negative trial-by-trial correlations, revealing antagonistic dynamics. Consistently, channelrhodopsin-assisted circuit mapping uncovered a disynaptic inhibitory pathway from cholinergic to dopaminergic neurons. Chemogenetic suppression of cholinergic activity disrupted dopaminergic prediction error signaling, reduced punishment-induced suppression of dopamine release, and impaired learning. These results demonstrate that prediction error signaling is jointly implemented by coordinated interactions between major neuromodulatory systems, challenging the prevailing view of their functional independence and revealing coordinated cross-system interactions as an organizing principle of reinforcement learning, with implications for neuropsychiatric disease 4-6.

neuroscience↗

bioRxiv2021

In vitro determination of inhibitory effects by humic substances complexing Zn and Se on SARS-CoV-2 virus replication

Humic substances are well known human nutritional supplement materials and play important performance-enhancing roles as animal feed additives, too. For decades, ingredients of humic substances have also been proven to carry potent antiviral effects against different viruses. Here, the antiviral activity of a humic substance containing ascorbic acid, Se- and Zn2+ ions intended as a nutritional supplement material was investigated against SARS-CoV-2 virus B1.1.7 Variant of Concern ("Alpha Variant") in a VeroE6 cell line. Results show that this combination has a significant in vitro antiviral effect at a very low concentration range of its intended active ingredients. Even picomolar concentration ranges of humic substances, vitamin C and Zn/Se ions in the given composition were enough to achieve fifty percent viral replication inhibition in the applied SARS-CoV-2 virus inhibition test.

microbiology↗

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↗

bioRxiv2020

In Vivo Localization of Deep Brain Implants in Mice

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges even for expert operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to the gold standard histological reconstruction. Adjustment of the recording depth with electrode microdrives or early termination of unsuccessful experiments saves many working hours, while fast 3-dimensional feedback helps surgeons to avoid systematic errors. Increased aiming precision will allow more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical layers.

neuroscience↗