Biology subjects

Bahn, S.

Publications and source records attributed to Bahn, S..

6 recordsLinked to original sources

bioRxiv2025

Design of Multichannel Transcranial Temporal Interfering Stimulation System Using an Individual MRI

Transcranial temporal interfering stimulation (tTIS) is an electrical stimulation method, in which two high-frequency alternating electric fields generate interference in the deep brain. This study aimed to design and verify the performance of a system that can precisely stimulate the deep brain using a multichannel tTIS based on an MRI image of an individuals brain. The optimization process, based on the parallel genetic algorithm with a GPU, was computationally verified using a modeled head that housed the deep brain. The hardware digitally stimulated the pre-interpreted head in a calculative manner, and the performance of the method was verified using an ideal head circuit. When four or more electrodes per frequency were used to stimulate the left thalamus, the rate of misstimulation was controlled to less than 2% on average for approximately 1 min. In the absence of deep-brain modeling, the average stimulus applied was reduced to 77.9%. The predicted signal had a 98.21% coefficient of determination for the modulations obtained by stimulating a head-type circuit using the proposed hardware. We designed a system that can stimulate the deep region of the brain through a multichannel tTIS, with due consideration for its practical application during the entire process. CCS CONCEPTS: * Theory and algorithms for application domains [->] Theory and algorithms for application domains; * Computing methodologies [->] Modeling and simulation; * Applied computing [->] Physical sciences and engineering

bioengineering↗

bioRxiv2025

Thalamofrontal synaptic weakening underlies short-term memory deficits from adolescent NMDAR hypofunction

N-methyl-D-aspartate receptor (NMDAR) hypofunction is linked to schizophrenia, but prevailing models centered on reduced number and activity of inhibitory interneurons, and the resulting excitation-inhibition (E-I) imbalance, do not explain selective cognitive impairments. Here, we show that repeated adolescent NMDAR antagonism produces short-term memory (STM) deficits by weakening thalamofrontal (TF) synaptic transmission. In mice repeatedly exposed to ketamine, STM impairment coincided with reduced release probability and vesicle refilling at mediodorsal thalamus (MD) [->] dorsomedial prefrontal cortex (dmPFC) synapses, without detectable changes in layer 2/3 [->] layer 2/3 synaptic release probability, intrinsic excitability, or synaptic ultrastructure. These presynaptic deficits were accompanied by diminished direction-selective population coding in the dmPFC, as revealed by decoding analysis, and impaired delayed alternation performance in the Y-maze. Chemogenetic strengthening of MD [->] dmPFC projections restored both neural selectivity and behavior. Our findings identify a circuit-specific presynaptic mechanism linking adolescent NMDAR hypofunction to cognitive dysfunction, challenging interneuron-centric models and establishing TF synapses as a potential therapeutic target in NMDAR-related disorders.

neuroscience↗

bioRxiv2024

Meta-Analysis of Urinary Metabolite GWAS Studies IdentifiesThree Novel Genome-Wide Significant Loci

Genome-wide association studies (GWAS) have substantially enhanced the understanding of genetic influences on phenotypic outcomes; however, realizing their full potential requires an aggregate analysis of numerous studies. Here we represent the first comprehensive meta-analysis of urinary metabolite GWAS studies, aiming to consolidate existing data on metabolite-SNP associations, evaluate consistency across studies, and unravel novel genetic links. Following an extensive literature review and data collection through the EMBL-EBI GWAS Catalog, PubMed, and metabolomix.com, we employed a sample size-based meta-analytic approach to evaluate the significance of previously reported GWAS associations. Our results showed that 1226 SNPs are significantly associated with urinary metabolite levels, including 48 lead SNPs correlated with 14 analytes: alanine, 3-aminoisobutyrate, betaine, creatine, creatinine, formate, glycine, glycolate, histidine, 2-hydroxybutyrate, lysine, threonine, trimethylamine, and tyrosine. Notably, the results revealed three previously unknown associations: rs4594899 with tyrosine (P = 6.6 x 10-9, N = 5447), rs1755609 with glycine (P = 3.3 x 10-10, N = 5447), and rs79053399 with 3-aminoisobutyrate (P = 6.9 x 10-10, N = 4656). These findings underscore the potential of urinary metabolite GWAS meta-analyses in revealing novel genetic factors that may aid in the understanding of disease processes, and highlight the necessity for larger and more comprehensive future studies. Author summaryIn this extensive study, weve meta-analysed data from various genome-wide association studies to better understand the genetic determinants of urinary metabolite levels. These metabolites are small molecules found in urine that reflect our bodys biochemical activities and can indicate states of health or disease. By combining results from previous research, weve identified 48 significant independent associations between single nucleotide polymorphisms (SNPs) and the levels of 14 metabolites in urine. Among these, we highlight three novel SNP-metabolite associations that offer new insights into the genetic architecture underlying metabolite regulation. Our findings contribute to the growing body of evidence that demonstrates the value of large-scale genetic meta-analyses. The significant SNP-metabolite links uncovered may serve as biomarkers for complex biological processes and disease mechanisms. This work takes us a step closer to a more nuanced understanding of the genetic factors that influence metabolic pathways and holds promise for improving diagnostic and therapeutic strategies through precision medicine. However, the complexity of genetic contributions to metabolite variations calls for continued research, underscoring the need for larger and more comprehensive studies in the future.

genetics↗

bioRxiv2023

A cerebellar disinhibitory circuit supports synaptic plasticity

How does the cerebellum learn how to control motion? The cerebellar motor learning critically depends on the long-term depression of the synapses between granule cells and Purkinje cells, which encode motor commands and inhibitory modifications to motor outputs, respectively, for simultaneous granule cell inputs and climbing fibre inputs, the latter of which encode the error signals1-3. However, recent studies have revealed that inhibitory inputs to Purkinje cells may disrupt long-term depression4-8, and it is not clear how long-term depression can occur without disruption. In search of a clue, we investigated the synaptic connectivity among the neurons reconstructed from serial electron microscopy images of the cerebellar molecular layer9,10. We discovered synapses between climbing fibres and a subset of inhibitory interneurons, which synapse onto the remaining interneurons, which in turn synapse onto Purkinje cells. Such connectivity redefines the interneuron types, which have been defined morphologically or molecularly11-13. Together with climbing fibres to Purkinje cell connections, those cell types form a feedforward disinhibitory circuit14. We argued that this circuit secures long-term depression by suppressing inhibition whenever climbing fibre input is provided and long-term depression needs to occur15, and we validated the hypothesis through a computational model. This finding implies a general principle of circuit mechanism in which disinhibition supports synaptic plasticity16,17.

neuroscience↗

bioRxiv2020

Synapses from the high-order thalamic nucleus and motor cortex are co-clustered spatially in the distal tuft dendrites of the somatosensory cortex

The posterior medial nucleus of the thalamus (POm) and vibrissal primary motor cortex (vM1) convey essential information to the barrel cortex (S1BF) regarding whisker position and movement. Therefore, understanding the relative spatial relationships of these two inputs is critical prerequisites to acquire insight into how S1 synthesizes information to interpret the location of an object. Using array tomography, we identified the locations of synapses from vM1 and POm on distal tuft dendrites of L5 pyramidal neurons. We found that synapses from vM1 and POm are spatially clustered on the same set of dendrites with unusually high density. Furthermore, the clusters of vM1 and POm synapses colocalize each other. These findings suggest that synaptic clusters, but not dendritic branches, act as functional units and cooperatively contribute to nonlinear dendritic responses.

neuroscience↗

bioRxiv2017

Insights into the molecular changes associated with postnatal human brain development: an integrated transcriptomics and proteomics study

Healthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data. We detected 911 proteins by liquid chromatography-mass spectrometry, and 83 were significantly associated with postnatal age (FDR p < 0.05). Network analysis identified three modules of co-regulated proteins correlated with age, including two modules with increasing expression involved in gliogenesis and NADH-metabolism and one neurogenesis-related module with decreasing expression throughout development. Integration with paired transcriptome data revealed that these age-related protein modules overlapped with RNA modules and displayed collinear developmental trajectories. Importantly, RNA expression profiles that are dynamically regulated throughout cortical development display tighter correlations with their respective translated protein expression compared to those RNA profiles that are not. Moreover, the correspondence between RNA and protein expression significantly decreases as a function of cortical aging, especially for genes involved in myelination and cytoskeleton organization. Finally, we used this data resource to elucidate the functional impact of genetic risk loci for intellectual disability, converging on gliogenesis, myelination and ATP-metabolism modules in the proteome and transcriptome. We share all data in an interactive, searchable companion website. Collectively, our findings reveal dynamic aspects of protein regulation and provide new insights into brain development, maturation and disease.

neuroscience↗