Biology subjects

Kwak, D.

Publications and source records attributed to Kwak, D..

5 recordsLinked to original sources

bioRxiv2025

Impaired Spatiotemporal Encoding of Social Behavior and Anxiety in the Prefrontal Cortex of Mice Lacking ASD-Risk Gene Shank3.

The prefrontal cortex is a central regulator of complex behaviors, including social interaction and anxiety-related behaviors. The prefrontal cortex encodes these behaviors using heterogeneous groups of neurons, or ensembles, which collectively process inputs and communicate with distributed brain regions. We examined whether loss of the Autism-risk gene Shank3 alters the recruitment of neurons encoding socioemotional behavior collectively, or if abnormal activity during specific behaviors might affect functionally or anatomically defined populations of neurons. To do this, we combined spatially-resolved microendoscopic calcium imaging across the prefrontal microcircuit with functionally defined labeling of neurons as control and mutant mice engaged in social interaction or anxiety-provoking behaviors. We then utilized a non-biased transcriptomic method to identify neurons activated by social interactions. We show that the recruitment of heterogeneous neuronal populations are altered in a cell type and spatially dependent manner by loss of Shank3, with impaired recruitment of behavior-specific activity patterns within superficial, but not deeper aspects of the prefrontal cortex.

neuroscience↗

bioRxiv2025

Co-release of opposing signaling molecules from cortical neurons controls the escalation and release of aggression

Neuropeptides exert broad effects across the brain to influence behavior. However, the mechanism by which the brain uses neuropeptide signaling to exert top-down control over complex behavioral responses remains poorly understood. Prolonged social isolation induces a distinct internal state that results in sweeping changes to behavior, including increased aggression. Here, we find that isolation-induced aggression activates Tachykinin-2 expressing (Tac2+) neurons in the mouse medial prefrontal cortex (mPFC). Genetic characterization of Tac2+ cells in the mPFC reveals them to be a population of unexplored GABAergic neurons. In-depth behavioral analyses combined with in vivo recordings of neural activity demonstrate that mPFC Tac2+ neurons are tuned to distinct phases of isolation-induced aggression: investigatory behaviors that escalate to attack (aggression escalation) and attack itself (aggression release). Loss-of-function perturbations targeting the release of either Neurokinin B (NkB), the stimulatory peptide encoded by Tac2, or the inhibitory neurotransmitter, GABA, reveal that these signaling molecules exert dissociable control over aggression escalation and release. These findings identify distinct roles for opposing signaling molecules co-released from the same population of cells. This suggests a surprising neurochemical mechanism by which neuropeptidergic populations in the prefrontal cortex exert top-down influence over complex behavior via the co-release of signaling molecules with opposing actions but coordinated impacts on behavior.

neuroscience↗

bioRxiv2025

Persistent interferon signaling that causes sensory neuron plasticity and pain in arthritis

While the inflammatory processes in rheumatoid arthritis have been described, mechanisms driving pain are poorly defined. Here, we used a multitude of approaches to uncover the neural basis, mediators, intracellular signaling pathway and the mechanism of inflammatory pain. In cartilage autoantibody-induced arthritis mice, an early immune-activation and a cytokine storm were mainly driven by vascular cells and monocyte/macrophages in the dorsal root ganglion. However, persistently elevated interferons and receptor-activation of the MNK1/2-eIF4E signaling pathway at all disease phases caused sensory-motor dysfunction and pain by inducing hyperexcitability and sensitization of Gfra3+ sensory neurons. Like mice, human sensory neurons expressed interferon receptors and interferons were elevated only in individuals with painful rheumatoid arthritis. Signaling pathway inhibition in vivo reversed pain and restored limb function. The finding that joint pain before and during arthritis is caused by a defined cytokine and signaling pathway holds promise for targeted therapies for pain relief in arthritis.

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

Music for cells? A systematic review of studies investigating the effects of audible sound played through speaker-based systems to cell cultures.

There have been several studies investigating whether musical sound can be used as cell stimuli in recent years. We systematically searched publications to get an overview of studies that have used audible sound played through speaker-based systems to induce mechanical perturbation in cell cultures. A total of 12 studies were identified. We focused on the experimental setups, the sound materials used as stimuli, and the outcomes. The stimuli were categorized into simple and complex sounds. The effects were reported as enhanced cell migration, proliferation, colony formation, and differentiation ability. However, there are significant differences in methodologies and cell type-specific outcomes, which made it difficult to find a systematic pattern in the results. We suggest that future experiments should consider using: 1) a more controlled acoustic environment), 2) standardized sound and noise measurement methods, and 3) a more comprehensive range of controlled sound stimuli.

cell biology↗