Biology subjects

Huang, S. C.

Publications and source records attributed to Huang, S. C..

3 recordsLinked to original sources

bioRxiv2025

Intrinsic fluctuations in global connectivity reflect transitions between states of high and low prediction error

While numerous researchers claim that the minimization of prediction error (PE) is a general force underlying most brain functions, others argue instead that PE minimization drives low-level, sensory-related neuronal computations but not high-order, abstract cognitive operations. We investigated this issue using behavioral, fMRI, and EEG data. Studies 1A/1B examined semantic- and reward-processing PE using task-fMRI, yielding converging evidence of PEs global effects on large-scale connectivity: high-PE states broadly upregulated ventral-dorsal connectivity, and low-PE states upregulated posterior-anterior connectivity. Investigating whether these global patterns characterize cognition generally, Studies 2A/2B used resting-state fMRI and showed that individuals continuously fluctuate between ventral-dorsal (high-PE) and posterior-anterior (low-PE) dynamic connectivity states. Additionally, individual differences in PE task responses track differences in resting-state fluctuations, further endorsing that these fluctuations represent PE minimization at rest. Finally, Study 3 combined fMRI and EEG data, and the study found that the fMRI fluctuation amplitude correlates most strongly with EEG power at 3-6 Hz, consistent with the PE network fluctuations occurring at Delta/Theta oscillation speeds. This whole-brain layout and timeline together are consistent with high/low-PE fluctuations playing a role in integrative and general sub-second cognitive operations.

neuroscience↗

bioRxiv2024

Molecular Signatures for Microbe-Associated Colorectal Cancers

BackgroundGenetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics. MethodsA Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on Fusobacterium nucleatum (Fn), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice (CPC-APCMin+/-) and patients (FAP, Lynch Syndrome, PJS, and JPS). ResultsThe MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon Fn infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon Fn infection was higher in CPC-APCMin+/- organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs. ConclusionsComputational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.

microbiology↗

bioRxiv2020

A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are linked to impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning. Author summaryThe primary cilium is a microtubule-based membranous projection on the cell that is involved in multiple physiological functions. Patients who have cilia dysfunction commonly have intellectual disability. However, it is not known how cilia affect learning and memory. Studying mouse models of a cilia-based intellectual disability can provide insight into learning and memory. One such cilia-based intellectual disability is Bardet-Biedl Syndrome (BBS), which is caused by homozygous and compound heterozygous mutations of BBS genes. We found that a mouse model of BBS (Bbs1M390R/M390R mice) has learning and memory defects. In addition, we found that other mouse models of BBS have similar learning and memory defects. These BBS mouse models have difficulty associating an environment with an aversive stimulus, a task designed to test context fear memory. This type of memory involves the hippocampus. We found that Bbs1M390R/M390R mice have decreased cell production in the hippocampus. Treating Bbs1M390R/M390R mice with a compound (lithium) that increases cell production in the hippocampus improved the learning and memory deficits. Our results demonstrate a potential role for cilia in learning and memory, and indicate that lithium is a potential treatment, requiring further study, for the intellectual disability phenotype of BBS.

animal behavior and cognition↗