Biology subjects

Choi, M.-K.

Publications and source records attributed to Choi, M.-K..

4 recordsLinked to original sources

bioRxiv2023

Automated cell annotation in multi-cell images using an improved CRF_ID algorithm

Cell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance in C. elegans whole-brain images (Chaudhary et al, 2021). However, because the method was optimized for whole-brain imaging, comparable performance could not be guaranteed for application in commonly used C. elegans multi-cell images that display a subpopulation of cells. Here, we present an advance CRF_ID 2.0 that expands the generalizability of the method to multi-cell imaging beyond whole-brain imaging. To illustrate the application of the advance, we show the characterization of CRF_ID 2.0 in multi-cell imaging and cell-specific gene expression analysis in C. elegans. This work demonstrates that high accuracy automated cell annotation in multi-cell imaging can expedite cell identification and reduce its subjectivity in C. elegans and potentially other biological images of various origins.

bioengineering↗

bioRxiv2023

Developmental Glucocorticoid exposure in zebrafish primes expression of genes linked to human psychiatric disorders

Early life stress (ELS) is one of the strongest risk factors for developing psychiatric disorders in humans. As conserved key stress hormones of vertebrates, glucocorticoids (GCs) are thought to play an important role in mediating the effects of ELS exposure in shaping adult phenotypes. In this process, early exposure to high level of GCs may induce molecular changes that alter developmental trajectory of an animal and primes differential adult responses. However, comprehensive characterization of identities of molecules that are targeted by developmental GC exposure is currently lacking. In our study, we describe lifelong molecular consequences of high level of developmental GC exposure using an optogenetic zebrafish model. First, we developed a new double-hit stress model using zebrafish by combining exposure to a high endogenous GC level during development and acute adulthood stress exposure. Our results establish that similar to ELS-exposed humans and rodents, developmental GC exposed zebrafish model shows altered behavior and stress hypersensitivity in adulthood. Second, we generated time-series gene expression profiles of the brains in larvae, in adult, and upon stress exposure to identify molecular alterations induced by high developmental GC exposure at different developmental stages. Third, we identify a set of GC-primed genes that show altered expression upon acute stress exposure only in animals exposed to a high developmental GC. Interestingly, our datasets of GC primed genes are enriched in risk factors identified for human psychiatric disorders. Lastly, we identify potential epigenetic regulatory elements and associated post-transcriptional modifications following high developmental GC exposure. Thus, we present a translationally relevant zebrafish model for studying stress hypersensitivity and alteration of behavior induced by exposure to elevated GC levels during development. Our study provides comprehensive datasets delineating potential molecular targets underlying the impact of developmental high GC exposure on adult responses.

neuroscience↗

bioRxiv2021

Redundant neural circuits regulate olfactory masking

Olfactory masking is a complex olfactory response found in humans. However, the mechanisms whereby the presence of one odorant masks the sensory and behavioral responses elicited by another odorant are poorly understood. Here, we report that Caenorhabditis elegans displays olfactory masking and that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly masks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde that signals food. Using a forward genetic screen, we found that several genes, osm-5, osm-1, and dyf-7, known to regulate the structure and function of sensory neurons played a critical role in olfactory masking. Loss of these genes mildly reduces the response to 2-nonanone and disrupts the masking effect of 2-nonanone. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue olfactory masking. AWB is activated by the removal of 2-nonanone stimulation or the onset of IAA; however, the mixture of 2-nonanone and IAA stimulates AWB similarly as 2-nonanone alone, masking the cellular effect of IAA. The latency of the AWB response is critical for the masking effect. Thus, our results identify redundant neural circuits that regulate the robust masking effect of a repulsive odorant and uncover the neuronal and cellular basis for this complex olfactory task. AUTHOR SUMMARYIn their natural environment, animals, including humans, encounter complex olfactory stimuli. However, regardless how complex the stimuli are, the behavioral output can only be one. Thus, how the brain processes multiple sensory cues to generate a coherent behavioral output is critical for the survival of the animal. In the present study, we combined molecular cellular genetics, optical physiology and behavioral analysis to study olfactory masking, a common olfactory phenomenon in which the presence of one odorant masks the stimulation of another odorant. Our results show that olfactory masking is regulated by redundant neuronal circuits, a mechanism that likely ensures the robust behavioral response to the sensory cue representing information critical for the survival.

neuroscience↗

bioRxiv2018

A collective modulatory basis for multisensory integration in C. elegans

In the natural environment, animals often encounter multiple sensory cues that are simultaneously present. The nervous system integrates the relevant sensory information to generate behavioral responses that have adaptive values. However, the signal transduction pathways and the molecules that regulate integrated behavioral response to multiple sensory cues are not well defined. Here, we characterize a collective modulatory basis for a behavioral decision in C. elegans when the animal is presented with an attractive food source together with a repulsive odorant. We show that distributed neuronal components in the worm nervous system and several neuromodulators orchestrate the decision-making process, suggesting that various states and contexts may modulate the multisensory integration. Among these modulators, we identify a new function of a conserved TGF-{beta} pathway that regulates the integrated decision by inhibiting the signaling from a set of central neurons. Interestingly, we find that a common set of modulators, including the TGF-{beta} pathway, regulate the integrated response to the pairing of different foods and repellents. Together, our results provide insights into the modulatory signals regulating multisensory integration and reveal potential mechanistic basis for the complex pathology underlying defects in multisensory processing shared by common neurological diseases.\n\nAuthor SummaryThe present study characterizes the modulation of a behavioral decision in C. elegans when the worm is presented with a food lawn that is paired with a repulsive smell. We show that multiple sensory neurons and interneurons play roles in making the decision. We also identify several modulatory molecules that are essential for the integrated decision when the animal faces a choice between the cues of opposing valence. We further show that many of these factors, which often represent different states and contexts, are common for behavioral decisions that integrate sensory information from different types of foods and repellents. Overall, our results reveal a collective molecular and cellular basis for integration of simultaneously present attractive and repulsive cues to fine-tune decision-making.

neuroscience↗