Minsoo Kim

All Publications

• Hemispherically lateralized rhythmic oscillations in the cingulate-amygdala circuit drive affective empathy in mice. Neuron Kim, S., Kim, M., Baek, J., Latchoumane, C., Gangadharan, G., Yoon, Y., Kim, D., Lee, J. H., Shin, H. 2022

  Abstract

  Observational fear, a form of emotional contagion, is thought to be a basic form of affective empathy. However, the neural process engaged at the specific moment when socially acquired information provokes an emotional response remains elusive. Here, we show that reciprocal projections between the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) in the right hemisphere are essential for observational fear, and 5-7Hz neural oscillations were selectively increased in those areas at the onset of observational freezing. A closed-loop disruption demonstrated the causal relationship between 5-7Hz oscillations in the cingulo-amygdala circuit and observational fear responses. The increase/decrease in theta power induced by optogenetic manipulation of the hippocampal theta rhythm bi-directionally modulated observational fear. Together, these results indicate that hippocampus-dependent 5-7Hz oscillations in the cingulo-amygdala circuit in the right hemisphere are the essential component of the cognitive process that drives empathic fear, but not freezing, in general.

  View details for DOI 10.1016/j.neuron.2022.11.001

  View details for PubMedID 36460007

• SELENBP1 overexpression in the prefrontal cortex underlies negative symptoms of schizophrenia. Proceedings of the National Academy of Sciences of the United States of America Kim, S., Kim, S. W., Bui, M. A., Kim, Y., Kim, M., Park, J. C., Kim, N. H., Pyeon, G. H., Jo, Y. S., Jang, J., Koh, H. Y., Jeong, C. H., Kang, M., Kang, H. J., Lee, Y. W., Stockmeier, C. A., Seong, J. K., Woo, D. H., Han, J. S., Kim, Y. S. 2022; 119 (51): e2203711119

  Abstract

  The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels of SELENBP1 transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressing Selenbp1 in the FC were assessed. SELENBP1 transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressing Selenbp1 in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia.

  View details for DOI 10.1073/pnas.2203711119

  View details for PubMedID 36512497

  View details for PubMedCentralID PMC9907074

• Affective empathy and prosocial behavior in rodents CURRENT OPINION IN NEUROBIOLOGY Kim, S., Kim, M., Shin, H. 2021; 68: 181-189

  Abstract

  Empathy is an essential function for humans as social animals. Emotional contagion, the basic form of afffective empathy, comprises the cognitive process of perceiving and sharing the affective state of others. The observational fear assay, an animal model of emotional contagion, has enabled researchers to undertake molecular, cellular, and circuit mechanism of this behavior. Such studies have revealed that observational fear is mediated through neural circuits involved in processing the affective dimension of direct pain experiences. A mouse can also respond to milder social stimuli induced by either positive or negative emotional changes in another mouse, which seems not dependent on the affective pain circuits. Further studies should explore how different neural circuits contribute to integrating different dimensions of affective empathy.

  View details for DOI 10.1016/j.conb.2021.05.002

  View details for Web of Science ID 000668571600022

  View details for PubMedID 34091136

• Spatial and temporal diversity of glycome expression in mammalian brain PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lee, J., Ha, S., Kim, M., Kim, S., Yun, J., Ozcan, S., Hwang, H., Ji, I., Yin, D., Webster, M. J., Weickert, C., Kim, J., Yoo, J., Grimm, R., Bahn, S., Shin, H., An, H. 2020; 117 (46): 28743-28753

  Abstract

  Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.

  View details for DOI 10.1073/pnas.2014207117

  View details for Web of Science ID 000591360600002

  View details for PubMedID 33139572

  View details for PubMedCentralID PMC7682437

• Neural circuits underlying a psychotherapeutic regimen for fear disorders NATURE Baek, J., Lee, S., Cho, T., Kim, S., Kim, M., Yoon, Y., Kim, K., Byun, J., Kim, S., Jeong, J., Shin, H. 2019; 566 (7744): 339-+

  Abstract

  A psychotherapeutic regimen that uses alternating bilateral sensory stimulation (ABS) has been used to treat post-traumatic stress disorder. However, the neural basis that underlies the long-lasting effect of this treatment-described as eye movement desensitization and reprocessing-has not been identified. Here we describe a neuronal pathway driven by the superior colliculus (SC) that mediates persistent attenuation of fear. We successfully induced a lasting reduction in fear in mice by pairing visual ABS with conditioned stimuli during fear extinction. Among the types of visual stimulation tested, ABS provided the strongest fear-reducing effect and yielded sustained increases in the activities of the SC and mediodorsal thalamus (MD). Optogenetic manipulation revealed that the SC-MD circuit was necessary and sufficient to prevent the return of fear. ABS suppressed the activity of fear-encoding cells and stabilized inhibitory neurotransmission in the basolateral amygdala through a feedforward inhibitory circuit from the MD. Together, these results reveal the neural circuit that underlies an effective strategy for sustainably attenuating traumatic memories.

  View details for DOI 10.1038/s41586-019-0931-y

  View details for Web of Science ID 000459119200038

  View details for PubMedID 30760920

• Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions NATURE COMMUNICATIONS Jung, H., Kim, S., Kim, M., Hong, J., Yu, D., Kim, J., Lee, Y., Kim, S., Woo, D., Shin, H., Park, B., Heo, W. 2019; 10: 314

  Abstract

  Spatiotemporal control of gene expression or labeling is a valuable strategy for identifying functions of genes within complex neural circuits. Here, we develop a highly light-sensitive and efficient photoactivatable Flp recombinase (PA-Flp) that is suitable for genetic manipulation in vivo. The highly light-sensitive property of PA-Flp is ideal for activation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. In addition, PA-Flp can be extended to the Cre-lox system through a viral vector as Flp-dependent Cre expression platform, thereby activating both Flp and Cre. Finally, we demonstrate that PA-Flp-dependent, Cre-mediated Cav3.1 silencing in the medial septum increases object-exploration behavior in mice. Thus, PA-Flp is a noninvasive, highly efficient, and easy-to-use optogenetic module that offers a side-effect-free and expandable genetic manipulation tool for neuroscience research.

  View details for DOI 10.1038/s41467-018-08282-8

  View details for Web of Science ID 000456010800011

  View details for PubMedID 30659191

  View details for PubMedCentralID PMC6338782

• Neonatal influenza infection causes pathological changes in the mouse brain VETERINARY RESEARCH Yu, J., Kim, M., Lee, J., Chang, B., Song, C., Nahm, S. 2014; 45: 63

  Abstract

  Influenza A virus infections have been proposed to be associated with a broad spectrum of central nervous system complications that range from acute encephalitis/encephalopathy to neuropsychiatric disorders in humans. In order to study early influenza virus exposure in the brain, we created an influenza-infection model in neonatal mice to investigate infection route and resulting pathological changes in the brain. Real-time polymerase chain reaction and immunohistochemical analyses showed that influenza virus infection induced by an intraperitoneal injection was first detected as early as 1 day post infection (dpi), and the peak infection was observed at 5 dpi. The viral antigen was detected in a wide range of brain regions, including: the cerebral cortex, hippocampus, cerebellum, and brainstem. Apoptotic cell death and gliosis were detected in the areas of viral infection. Significant increases in proinflammatory cytokine expression were also observed at 5 dpi. Viral RNAs were detected in the cerebrospinal fluid of infected adult mice as early as 1 dpi. In addition, many infected cells were observed near the ventricles, indicating that the virus may enter the brain parenchyma through the ventricles. These results demonstrate that influenza virus may effectively infect broad regions of the brain through the hematogenous route, potentially through the cerebrospinal fluid along the ventricles, and subsequently induce neuropathological changes in the neonatal mouse brain.

  View details for DOI 10.1186/1297-9716-45-63

  View details for Web of Science ID 000338576000001

  View details for PubMedID 24917271

  View details for PubMedCentralID PMC4063221

• Effect of Harderian adenectomy on the statistical analyses of mouse brain imaging using positron emission tomography JOURNAL OF VETERINARY SCIENCE Kim, M., Woo, S., Yu, J., Lee, Y., Kim, K., Kang, J., Eom, K., Nahm, S. 2014; 15 (1): 157-161

  Abstract

  Positron emission tomography (PET) using 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains.

  View details for DOI 10.4142/jvs.2014.15.1.157

  View details for Web of Science ID 000333503900018

  View details for PubMedID 23820224

  View details for PubMedCentralID PMC3973759

• Comparative analyses of influenza virus receptor distribution in the human and mouse brains JOURNAL OF CHEMICAL NEUROANATOMY Kim, M., Yu, J., Lee, J., Chang, B., Song, C., Lee, B., Paik, D., Nahm, S. 2013; 52: 49-57

  Abstract

  Accumulating evidence suggests a potential link between influenza A virus infection and the occurrence of influenza-associated neurological disorders. As influenza infection is mediated by specific receptors on the host cell surface, it is important to understand the distribution patterns of influenza receptors in target organs. We carried out comprehensive experiments to localize influenza receptors in the brains of two different mouse strains and the human brain for comparison using lectin histochemistry. We further compared the brain regions in which influenza receptors were expressed and the regions in which experimental influenza infection was observed. Our results show that the expression patterns for influenza receptors in mouse and human brains are different. In the mouse brain, human influenza virus receptors (HuIV-R) were expressed in part of brainstem and cerebellar white matter while avian influenza virus receptors (AIV-R) were expressed in the cerebellar Purkinje neurons. In contrast, in the human brain, many neurons and glia in widespread regions, including the cerebral cortex, hippocampus, brainstem, and cerebellum, express both AIV-R and HuIV-R. Importantly, vascular endothelial cells, choroid plexus epithelial cells and ependymal cells in both mouse and human brains express high levels of HuIV-R and AIV-R. The regional reciprocity was not observed when comparing regions with influenza receptor expression and the regions of influenza infection within the mouse brain. Our results demonstrate a differential influenza receptor expression pattern in mouse and human brains, and a disparity between influenza receptor distribution and regions with actual influenza infection.

  View details for DOI 10.1016/j.jchemneu.2013.05.002

  View details for Web of Science ID 000325597300007

  View details for PubMedID 23726946