1. 3DeeCellTracker, a deep learning-based pipeline for segmenting and tracking cells in 3D time lapse images. Wen C, Miura T, Voleti V, Yamaguchi K, Tsutsumi M, Yamamoto K, Otomo K, Fujie Y, Teramoto T, Ishihara T, Aoki K, Nemoto T, Hillman EMC, *Kimura KD. eLife (2021) [Article] [EurekAlert!]
In modern basic life science research as well as in drug discovery, recording and analyzing the images of cells over time using 3D microscopy has become extremely important. Once the images have been recorded, the same cell in different images at different time points has to be accurately identified ("cell tracking") because the living cells captured in the images are in motion. However, tracking many cells automatically in 3D microscope videos has been considerably difficult.
Chentao Wen, a postdoc in our lab, and colleagues developed the 1st AI-based software called 3DeeCellTracker that can run on a desktop PC and automatically track cells in 3D microscope videos. Using the software, they were able to measure and analyze the activities of ~100 cells in the brain of a moving microscopic worm, in a naturally beating heart of a young small fish, and ~1000 cancer cells cultured in 3D under laboratory conditions, which were recorded with different types of cutting-edge microscope systems.
This versatile software can now be used across biology, medical research, and drug development to help monitor cell activities.
2. STEFTR: A hybrid versatile method for state estimation and feature extraction from the trajectory of animal behavior. Yamazaki SJ, Ohara K, Ito K, Kokubun N, Kitanishi T, Takaichi D, Yamada Y, Ikejiri Y, Hiramatsu F, Fujita K, Tanimoto Y, Yamazoe-Umemoto A, Hashimoto K, Sato K, Yoda K, Takahashi A, Ishikawa, Y, Kamikouchi A, Hiryu S, Maekawa, Kimura KD. Front Neurosci (2019) [Article]
Recording the movements of people and animals has become easy because of small GPS devices and video cameras. However, the reasons for such movements remain difficult to infer. We have developed a flexible artificial intelligence technology to understand the movement of animals, ranging from roundworms in petri dishes to penguins in the Antarctic Ocean. This method will make it easier to understand animal movements as well as their underlying brain activities.
3. Calcium dynamics regulating the timing of decision-making in C. elegans. Tanimoto Y, Yamazoe-Umemoto A, Fujita K, Kawazoe Y, Miyanishi Y, Yamazaki SJ, Fei X, Busch KE, Gengyo-Ando K, Nakai J, Iino Y, Iwasaki Y, Hashimoto K, Kimura KD. eLife (2017) [Article]
All animals make decisions according to information, but the detailed mechanism is not known. We found that, C. elegans chooses the direction in an odor space by mathematically integrating the information of odor concentration. Moreover, we also identified a gene responsible for the integration. Because integration of information has been known to be important for decision-making of more complex experimental animals such as monkeys, the gene for integration may also be important for decision-making even in humans.
4. In actio optophysiological analyses reveal functional diversification of dopaminergic neurons in the nematode C. elegans. Tanimoto Y, Zheng YG, Fei X, Fujie Y, Hashimoto K, Kimura KD. Sci Rep (2016) [Article]
Many neuronal groups such as dopamine-releasing (dopaminergic) neurons are functionally divergent, although the details of such divergence are not well understood. In this study, we revealed functional divergence within the dopaminergic neurons of C. elegans. Because dopaminergic neurons of the animals were supposedly activated by mechanical stimulus upon entry into a lawn of their food bacteria, we developed a novel integrated microscope system that can auto-track a freely-moving (in actio) C. elegans to individually monitor and stimulate the neuronal activities of multiple neurons. We found that only head-dorsal pair of dopaminergic neurons (CEPD), but not head-ventral or posterior pairs, were preferentially activated upon food entry. In addition, the optogenetic activation of CEPD neurons alone exhibited effects similar to those observed upon food entry. Thus, our results demonstrated functional divergence in genetically similar dopaminergic neurons, which may provide a new entry point toward understanding the functional diversity of neurons beyond genetic terminal identification.
5. Modulation of different behavioral components by neuropeptide and dopamine signalings in non-associative odor learning of Caenorhabditis elegans. Yamazoe-Umemoto, A, Fujita, K, Iino, Y, Iwasaki, Y, Kimura, KD. Neurosci Res (2015) [Article]
Multiple neuromodulators are involved in learning and memory. However, the differences and similarities in mechanisms underlying how each neuromodulator regulates behaviors in learning, are not well understood. We found that dopamine and neuropeptide signalings are both required for odor learning of the nematode C. elegans. Interestingly, quantitative behavioral and genetic analyses have indicated that neuropeptide and dopamine signalings are independently required for the acquisition and execution of memory, respectively. Such different roles of multiple neuromodulators in learning could be evolutionarily conserved.
6. Enhancement of odor-avoidance regulated by dopamine signaling. Kimura KD, Fujita K, Katsura I. J Neurosci (2010) [Article]
Plasticity in sensory responses is one of the fundamentals of neural function in animals. To develop an original behavioral paradigm for understanding the molecular and cellular basis of neural function of C. elegans, we investigated plasticity of odor avoidance of the animals. We found that C. elegans exhibits an enhancement of avoidance behavior to a repulsive odor 2-nonanone after preexposure to the odor, which may be beneficial for the animals by protecting them from further disturbance. In addition, genetic and pharmacological analyses revealed that the enhancement of 2-nonanone avoidance requires dopamine signaling via D2-like dopamine receptor DOP-3, which functions in a pair of RIC interneurons to regulate the enhancement. These results demonstrate a new genetic and pharmacological paradigm for non-associative enhancement of neural responses that is regulated by dopamine signaling.