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Hatakeyama, A.

Publications and source records attributed to Hatakeyama, A..

3 recordsLinked to original sources

In vivo deep-brain microscopy at submicrometer resolution with refractive index-matched prism interfaces

The mammalian brain is a thick and densely layered structure comprising a huge number of neurons that work together to process information and regulate brain functions. Although various optical methods have been developed to investigate deep brain dynamics, they are limited by technical constraints, invasiveness, suboptimal spatial resolution, and/or a restricted field of view. To overcome these limitations, we developed an implantable, optically optimized microprism interface with a refractive index matched to that of brain tissue and water, enabling minimally-invasive, wide-field two-photon imaging method with enhanced brightness and sub-micron resolution in deep prefrontal areas.

neuroscience↗

The transsulfuration pathway suppresses the embryonic lethalphenotype of glutathione reductase mutants in Caenorhabditis elegans

The gsr-1 gene encodes the only glutathione reductase in Caenorhabditis elegans and gsr-1 loss of function alleles have a fully penetrant embryonic lethal phenotype. Therefore, maintenance of glutathione redox homeostasis is essential for nematode survival. We report here that impairment of the nonsense-mediated mRNA decay (NMD) pathway suppresses the embryonic lethality of gsr-1 mutants, allowing their normal development and growth. This NMD pathway dependent suppression requires cth-1 and cth-2 that encode, respectively, two isoforms of cystathionine-{gamma}-lyase that catalyze the conversion of cystathionine to cysteine through the transsulfuration pathway. Interestingly, the thioredoxin system that can also provide cysteine through the cystine reduction pathway is not required for the suppression of the lethal phenotype of gsr-1 embryos when the NMD pathway is inactivated. Together, our data indicate that increasing the activity of the reverse transsulfuration pathway can compensate the detrimental effect of the gsr-1 mutation, raising the interesting question of why C. elegans has not preserved such compensatory mechanism to avoid the embryonic lethality of these mutants. HighlightsO_LIA novel cryptic deletion in the smg-3 gene suppresses the embryonic lethality of C. elegans gsr-1 mutants. C_LIO_LIInactivation of the nonsense-mediated mRNA decay (NMD) pathway allows survival of gsr-1 mutant worms. C_LIO_LIGenetic impairment of the transsulfuration pathway restores the embryonic lethal phenotype in gsr-1; smg-3 mutants. C_LI

genetics↗

Low-invasive, wide-field, and cellular resolution two-photon imaging of neural population activity in brainstem and nucleus tractus solitarii

Brain-viscera communication plays a crucial role in regulating mental health, with the vagus nerve being a key structure mediating this interaction. Clinically, artificial vagus nerve stimulation (VNS) is used to treat various neuropsychiatric disorders, highlighting the importance of vagal afferent fibers in regulating emotion. The nucleus tractus solitarii (NTS) is a brainstem structure proposed to receive signals from vagal afferents and relay them to brain networks for emotion regulation. However, due to the anatomical complexity and difficulty in accessing the deep-brain NTS region in living animals, the mechanisms remain unclear. Here, we developed a wide-field and deep-brain two-photon imaging method using a double-prism based optical interface. This approach enables the identification of cellular-resolution neural activities in the NTS while preserving the cerebellum, which covers the NTS and is important for emotion regulation, intact. We systematically evaluated how NTS neurons respond to VNS and a gastrointestinal hormone, suggesting the usefulness of this method for investigating the role of the vagus-NTS pathway in vivo.

neuroscience↗