Biology subjects

Choe, H. K.

Publications and source records attributed to Choe, H. K..

4 recordsLinked to original sources

bioRxiv2025

Master clock-thalamic-prefrontal circuit controls circadian social priority

Social behaviors arise from complex brain operations that adapt to changing social contexts and internal states. However, how internal states guide the resolution of competing social goals remains unclear. Here, we show that prioritization between competing instincts follows a circadian pattern via a circuit linking the suprachiasmatic nucleus (SCN) to the medial prefrontal cortex (mPFC). Specifically, SCNVIP neurons project to Vipr2-expressing neurons in the nucleus reuniens (RE), which innervate the mPFC to regulate social prioritization. Vipr2 signaling in the RE is essential for circadian modulation of appetitive and consummatory social behaviors, aligning social behaviors with clock-regulated reproductive system. Overall, this SCN-RE-mPFC circuit provides a neural principle through which the master clock coordinates the prefrontal cortex to resolve a conflict of motivated behaviors by referencing an internal state.

neuroscience↗

bioRxiv2023

An integrated single-cell transcriptome landscape of postnatal mouse hypothalamus

The neural stem cells (NSCs) in the hypothalamus are relatively more narrowly defined than in other neurogenic regions of the postnatal brain. By leveraging single-cell RNA sequencing (scRNA-seq) data, we generated an integrated reference dataset comprising 296,282 cells from postnatal hypothalamic regions and the adjacent region, bed nucleus of the stria terminalis (BNST), and identified 30 hypothalamic neuronal and non-neuronal cell populations. The analyses of their gene expression pattern, and specific differentiation trajectories reveal the presence of NSCs and intermediate progenitor cells (IPCs) that show a continuum of activation and differentiation processes in the hypothalamus after birth. Through comparative analyses of the integrated dataset with our lab-generated Connect-seq data obtained from the whole hypothalamus, we further assessed the technical validity of the dataset presented in this study. Our large-scale unified scRNA-seq dataset with harmonized cell-level metadata can serve as a valuable resource for investigating cell type-specific gene expression and cellular differentiation trajectories in the postnatal mouse hypothalamus.

neuroscience↗

bioRxiv2022

Social context modulates multibrain broadband dynamics and functional brain-to-brain coupling in the group of mice

Although mice are social animals, studies that explore the simultaneously recorded neural activities of multiple mice, especially in a social setting, are still lacking. In this study, we simultaneously recorded local field potential (LFP) signals in the dorsomedial prefrontal cortex (dmPFC) from up to four mice. The brain activities of the mice were measured in two contradicting conditions - freely interacting in a group or being individually separated. We found that social context and the locomotive states predominately modulate the entire LFP structure. Power spectral density (PSD) estimate and spectrogram of LFP signals showed a broadband modulation; lower frequency bands--delta (<4Hz), theta (4-7Hz), and alpha (8-12Hz) power were highly correlated to each other and anti-correlated with gamma and high gamma (>30Hz) power. We calculated the high-to-low-power ratio (HLR) and found that HLR was higher when the mice were in a group than were separated. The HLR was also higher when they were active--whether or not they were moving. The mice in the group showed higher HLR in any locomotive states. We then analyzed whether social context can be divided into sub-contexts. Notably, the aggregation of animals, called huddling, decreased social context-induced increase in HLR. Multibrain analyses of HLR indicated that the mice in the group displayed high cross-correlation to each other, indicating interbrain synchrony. Then we examined whether there is any directional relationship between HLR from pairs of mice. A majority of dyad selected within the group of mice showed unilateral precedence of HLR by Granger causality analysis, comprising a hierarchical social structure based on a directionality of influence. Overall, this study shows the importance of the social environment in brain dynamics and emphasizes the value of simultaneous multibrain recording for researching social behaviors and their neural correlates. One-sentence summaryCoexistence modulates overall brain activities with unilateral causal relationship.

neuroscience↗

bioRxiv2020

Single adeno-associated virus-based multiplexed CRISPR-Cas9 system to nullify core components of the mammalian molecular clock

ABSTRACTThe mammalian molecular clock is based on a transcription-translation feedback loop (TTFL) containing Period1, 2 (Per1, 2), Cryptochrome1, 2 (Cry1, 2), and Brain and Muscle ARNT-Like 1 (Bmal1). TTFL robustness is endowed by genetic complementation between these components; therefore, multiple genes must be knocked out to physiologically investigate the molecular clock, which requires extensive research resources. To facilitate molecular clock disruption, we developed a CRISPR-Cas9-based single adeno-associated viral (AAV) system targeting the circadian clock (CSAC) for Pers, Crys, or Bmal1. First, we designed single guide RNAs (sgRNAs) targeting individual clock genes using an in silico approach and validated their efficiency in Neuro2a cells. To target multiple genes, multiplex sgRNA plasmids were constructed using Golden Gate assembly and expressed in viral vectors. CSAC efficiency was demonstrated by decreased protein expression in vitro and ablated molecular oscillation ex vivo. We also measured locomotor activity and body temperature in Cas9-expressing mice injected with CSAC at the suprachiasmatic nucleus. Circadian rhythm disruption was observed under free-running conditions, indicating that CSAC can efficiently and robustly disrupt molecular circadian clock. Thus, CSAC is a simple and powerful tool for investigating the physiological role of the molecular clock in vivo.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗