Biology subjects

Yang, J.-W.

Publications and source records attributed to Yang, J.-W..

5 recordsLinked to original sources

bioRxiv2024

Progressive engagement of SST+ interneurons via Elfn1 regulates the barrel-septa response identity in the somatosensory cortex of mice

Just as separated digits and repeated sampling enhance somatosensation in humans, mice sense objects through multiple segregated whiskers through successive contacts. Individual whisker identity is maintained through the somatotopic organization of the Whisker[->]Brainstem[->]Thalamus[->]Cortex axis, culminating in distinct cortical domains: barrels and the surrounding septa. By performing simultaneous recordings using in-vivo electrophysiology in wild-type (WT) mice, we identify a progressive divergence in spiking activity between these domains upon repeated behaviorally relevant (10Hz) single- and multi-whisker stimulation. While the spiking activity ratio of multi- to single-whisker stimulation remains stable in barrels, it increases progressively in septa, suggesting inhibitory cell recruitment. Using genetic fate-mapping and tissue clearing, we indeed reveal that SST+ and VIP+ interneurons exhibit distinct laminar and regional distributions in barrel and septa domains. Further, calcium imaging of SST+ and VIP+ interneurons shows that while both neuron types respond to single-whisker stimulus, SST+ interneurons preferentially engage more in 10Hz multi-whisker stimulation, indicating their critical role in progressive stimulus preference. Genetic removal of Elfn1, which regulates the incoming excitatory synaptic dynamics onto SST+ interneurons, leads to the loss of the progressive increase in septal spiking ratio (MWS/SWS) upon stimulation. The importance of the loss of functional segregation of barrels, versus septa is revealed by cumulative temporal decoding analysis, supporting the notion that SST+ interneuron-mediated inhibition contributes to temporal encoding and stimulus integration. Finally, viral tracing combined with whole brain clearing and imaging reveals that barrel and septa domains project differentially to secondary somatosensory (S2) and motor (M1) cortices. These distinct projection patterns suggest that differential inhibitory processing in barrels and septa may contribute to functionally specialized downstream signaling. Together, our findings indicate that the progressive engagement of SST+ interneurons, mediated by Elfn1-dependent synaptic facilitation, underlies the preferential integration of multi-whisker stimuli in septa. This local inhibitory mechanism likely contributes to the functional segregation of barrel and septa domains and their distinct cortical projections, shaping how sensory information is processed and relayed to higher-order brain regions.

neuroscience↗

bioRxiv2023

Quantitative monitoring of neuronal regeneration by functional assay and wireless neural recording

Brain injury is heterozygous in nature and no single scheme is ideal for diagnosis and prognosis. Assessing proteins in cerebrospinal fluid is limited or not applicable after surgery whereas plasma biomarkers can only report occurrence of injury. The lack of regeneration markers renders the difficulty during drug discovery. This study aims to establish a potential reporter that correlates the regeneration progress of injured brain neurons. According to our recent publication, treatment of mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) could rescue motor function deficit of mice after traumatic brain injury. We thus measured the local field potential (LFP) at sites proximal to the injury region. The recorded neuronal activity reported stimulation of right forelimb of mice. Our experimental results indicate that the recovery of evoked LFP correlates with FCCP treatment and could potentially be used as a regeneration biomarker. These promising findings suggest future application of a wireless, non-invasive recording system as a potential companion diagnosis device during drug development.

bioengineering↗

bioRxiv2022

Haploid-resolved and chromosome-scale genome assembly in hexa-autoploid sweetpotato (Ipomoea batatas (L.) Lam)

Sweetpotato (Ipomoea batatas (L.) Lam) is the worlds seventh most important food crop by production quantity. Cultivated sweetpotato is a hexaploid (2n = 6x = 90), and its genome (B1B1B2B2B2B2) is quite complex due to polyploidy, self-incompatibility, and high heterozygosity. Here we established a haploid-resolved and chromosome-scale de novo assembly of autohexaploid sweetpotato genome sequences. Before constructing the genome, we created chromosome-scale genome sequences in I. trifida using a highly homozygous accession, Mx23Hm, with PacBio RSII and Hi-C reads. Haploid-resolved genome assembly was performed for a sweetpotato cultivar, Xushu18 by hybrid assembly with Illumina paired-end (PE) and mate-pair (MP) reads, 10X genomics reads, and PacBio RSII reads. Then, 90 chromosome-scale pseudomolecules were generated by aligning the scaffolds onto a sweetpotato linkage map. De novo assemblies were also performed for chloroplast and mitochondrial genomes in I. trifida and sweetpotato. In total, 34,386 and 175,633 genes were identified on the assembled nucleic genomes of I. trifida and sweetpotato, respectively. Functional gene annotation and RNA-Seq analysis revealed locations of starch, anthocyanin, and carotenoid pathway genes on the sweetpotato genome. This is the first report of chromosome-scale de novo assembly of the sweetpotato genome. The results are expected to contribute to genomic and genetic analyses of sweetpotato.

genomics↗

bioRxiv2022

Structural basis of organic cation transporter-3 inhibition

Organic cation transporters (OCTs) facilitate the translocation of catecholamines and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 [A] resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.

pharmacology and toxicology↗

bioRxiv2021

Identification of a developmental switch in information transfer between whisker S1 and S2 cortex in mice

The whiskers of rodents are a key sensory organ that provides critical tactile information for animal navigation and object exploration throughout life. Previous work has explored the developmental sensory-driven activation of the primary sensory cortex processing whisker information (wS1), also called barrel cortex. This body of work has shown that the barrel cortex is already activated by sensory stimuli during the first post-natal week. However, it is currently unknown when over the course of development these stimuli begin being processed by higher order cortical areas, such as secondary whisker somatosensory area (wS2). Here we investigate for the first time the developmental engagement of wS2 by sensory stimuli and the emergence of cortico-cortical communication from wS1 to wS2. Using in vivo wide-field imaging and electrophysiological recordings in control and conditional knock-out mice we find that wS1 and wS2 are able to process bottom-up information coming from the thalamus already right after birth. We identify that it is only at the end of the first post-natal week that wS1 begins to provide excitation into wS2, a connection which begins to acquire feed-forward inhibition characteristics after the second post-natal week. Therefore, we have uncovered a developmental window during which excitatory versus inhibitory functional connectivity between wS1 and wS2 takes place.

neuroscience↗