Biology subjects

Kang, Y.-J.

Publications and source records attributed to Kang, Y.-J..

3 recordsLinked to original sources

bioRxiv2024

Activation of hypoactive parvalbumin-positive fast-spiking interneuron restores dentate inhibition to prevent epileptiform activity in the mouse intrahippocampal kainate model of temporal lobe epilepsy

Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed PV immunostaining and whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. We found that the number of dentate PV+ cells was reduced in IHK treated mice. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) Spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) The amplitude of evoked IPSCs in DGCs by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous epileptiform activity in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished the epileptiform activity. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy. HighlightsO_LIReduced number of dentate PV+ interneurons in TLE mice C_LIO_LIPersistently reduced action potential firing rates of dentate PV+ interneurons in TLE mice C_LIO_LIEnhanced amplitude but decreased frequency of spontaneous IPSCs in the dentate gyrus in TLE mice C_LIO_LIIncreased amplitude of evoked IPSCs mediated by dentate PV+ interneurons in TLE mice C_LIO_LIChemogenetic activation of PV+ interneurons prevents epileptiform activity in TLE mice C_LI

neuroscience↗

bioRxiv2022

Markonv: a novel convolutional layer with inter-positional correlations modeled

Deep neural networks equipped with convolutional neural layers have been widely used in omics data analysis. Though highly efficient in data-oriented feature detection, the classical convolutional layer is designed with inter-positional independent filters, hardly modeling inter-positional correlations in various biological data. Here, we proposed Markonv layer (Markov convolutional neural layer), a novel convolutional neural layer with Markov transition matrices as its filters, to model the intrinsic dependence in inputs as Markov processes. Extensive evaluations based on both synthetic and real-world data showed that Markonv-based networks could not only identify functional motifs with inter-positional correlations in large-scale omics sequence data effectively, but also decode complex electrical signals generated by Oxford Nanopore sequencing efficiently. Designed as a drop-in replacement of the classical convolutional layer, Markonv layers enable an effective and efficient identification for inter-positional correlations from various biological data of different modalities. All source codes of a PyTorch-based implementation are publicly available on GitHub for academic usage.

bioinformatics↗

bioRxiv2021

A new method for obtaining bankable and expandable adult-like microglial cells

The emerging role of microglia in neurological disorders requires a novel method for obtaining massive amounts of adult microglia because current in vitro methods for microglial study have many limitations, including a limited proliferative capacity, low cell yield, immature form, and too many experimental animals use. Here, we developed a new method for obtaining bankable and expandable adult-like microglial cells using the head neuroepithelial layer (NEL) of mouse E13.5. The NEL includes microglia progenitors that proliferate and ramify over time. Functional validation with a magnetic-activated cell sorting system using the NEL showed that the isolated CD11b-positive cells (NEL-MG) exhibited microglial functions, such as phagocytosis (microbeads, amyloid {beta}, synaptosome), migration, and inflammatory changes following lipopolysaccharide (LPS) stimulation. NEL was subcultured and the NEL-MG exhibited a higher expression of microglia signature genes than the neonatal microglia, a widely used in vitro surrogate. Banking or long-term subculture of NEL did not affect NEL-MG characteristics. Transcriptome analysis revealed that NEL-MG exhibited better conservation of microglia signature genes with a closer fidelity to freshly isolated adult microglia than neonatal microglia. This new method effectively contributes to obtaining adult-like microglial cells, even when only a small number of experimental animals are available, leading to a broad application in neuroscience-associated fields.

neuroscience↗