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Nomoto, M.

Publications and source records attributed to Nomoto, M..

16 recordsLinked to original sources

Sleep neural code perpetuates the evolving negativity bias under stress

Negativity bias is the distorted cognitive processing of how self-experiences are negatively perceived through rumination and overgeneralization. Despite proposed theories of higher-order emotional representation and the involvement of default mode networks, the biological mechanisms underlying how negative emotional bias is persistently generated remain unknown. Here, we show that under negative emotional state, sleep orchestrates neural dynamics to shape persistent negativity bias. A negative emotional state, induced by repeated social defeat stress (SoD), generates negativity bias in both memory-recall and novel experiences such as fear conditioning. Longitudinal Ca2+ imaging of the hippocampus across days revealed that in emotional states, negative schema-like representations that encode the semantic aspect of negativity across experiences are generated. These negative schema-like representations are continuously processed along with dynamic co-reactivations of distinct emotional experiences during sleep. Closed-loop optogenetic silencing of stress experience-tagged cellular ensembles during sleep, but not during awake, prevents negativity bias in future memory-recall and novel experiences. Finally, sleep-active, but not sleep-nonactive, SoD cells predict and decode emotional behaviours during learned and novel situations. Together, these results reveal the biological emergence of semantic-like representations of emotional experiences and sleep causally coordinate neuronal dynamics to persistently shape negativity in future conscious states. These findings offer a new perspective on how higher-order emotional processing during sleep may determine our emotional interpretation of past and future experiences.

neuroscience↗

Cellular energy sensor SnRK1 suppresses salicylic acid-dependent and -independent defenses and bacterial resistance in Arabidopsis

In nature, plants cope with various pathogens that compete for cellular resources during infection. It has long been suggested that plant defense activity must be linked to cellular energy and metabolic states to optimize the balance between growth and defense. However, the molecular mechanisms that regulate immune activity in relation to cellular energy status remain unclear. Here, we demonstrate that the plant energy sensor SNF1-RELATED KINASE 1 (SnRK1) plays a critical role in modulating defense responses and bacterial resistance in Arabidopsis thaliana. Bacterial elicitor-induced expression of defense marker genes, such as PATHOGENESIS-RELATED 1 (PR1), is significantly repressed under sugar-limited conditions in wild-type seedlings, whereas this expression is markedly enhanced in the snrk1 knockdown mutants. SnRK1 restricts defense-related gene expression and resistance to the biotrophic bacterial pathogen Pseudomonas syringe pv. tomato DC3000, which are partly dependent on salicylic acid (SA). In addition, we found that the SnRK1 kinase activity is increased by high humidity. Consistently, SnRK1 is critical for the suppression of SA-mediated defense responses under high humidity conditions. SnRK1 physically associates with the SA-related transcription factors TGACG SEQUENCE-SPECIFIC BINDING PROTEIN 4 (TGA4) and TGA2 to attenuate PR1 expression. These findings provide valuable insight into the molecular mechanisms linking cellular energy status with immune regulation in plants.

plant biology↗

Actin Depolymerization Factors (ADFs) Moonlighting: Nuclear Immune Regulation by Interacting with WRKY Transcription Factors and Shaping the Transcriptome

Remodeling of the actin cytoskeleton is a critical process for plant immunity, essential for the transport, activation, and stabilization of immune-regulatory molecules and organelles. In this process, actin depolymerization factors (ADFs) function as key players through severing and depolymerizing actin microfilaments. However, recent evidence suggests that ADFs may possess non-canonical immune functions inside the nucleus, in addition to the canonic cytosolic role, a phenomenon not adequately explained by the traditional mechanistic model of ADF-actin dynamics. In this study, we demonstrate that Arabidopsis ADFs exhibit a moonlighting function in the nucleus, where they interact with transcriptional machinery to regulate the transcriptome during both the resting state and the immune responses. We show that ADF2/3/4 have redundant functions in defense against virulent and avirulent Pseudomonas syringae. Notably, it is nuclear - rather than cytosolic - ADFs that contribute to defense against P. syringae and mediate pro-immune transcription. Mechanistically, we demonstrate that nuclear ADFs interact with transcription factors, histone complexes, and other components of the transcriptional machinery. Specifically, ADF2/3/4 can form a complex with WRKY transcription factors, such as WRKY22/29/48, thereby directly regulating WRKY activity to shape the pro-immune transcriptome. In summary, our study reveals that ADFs moonlight as direct regulators of transcription factors, mediating a broad range of nuclear-cytoplasmic regulation in plant immunity and potentially other biological processes.

plant biology↗

The medial prefrontal cortex encodes procedural rules as sequential neuronal activity dynamics

The prefrontal cortex plays a crucial role in procedural rule learning; however, the specific neuronal mechanism through which it represents rules is unknown. We hypothesized that sequential neuronal activities in the prefrontal cortex encode these rules. To investigate this, we recorded neuronal activities in the medial prefrontal cortex of mice during rule learning using Ca2+ imaging. We utilized a method based on convolutional negative matrix factorization, iSeq, to automatically detect temporal neuronal sequences in the recorded data. As rule learning advanced, these neuronal sequences began to encode critical information for rule execution. In mice that had mastered the rule, the dynamics of neuronal sequences could predict success and failure of reward acquisition. Furthermore, the composition of cell populations within the neuronal sequences was rearranged throughout the learning process. These findings suggest that as animals learn a rule, the medial prefrontal cortex continually updates its neuronal sequences to assign significance to behavioral actions crucial for reward acquisition.

neuroscience↗

Dual roles of idling moments in past and future memories

Every day, we experience new daily episodes and store new memories. Although memories are stored in corresponding engram cells, how different sets of engram cells are selected for current and next episodes, and how they create their memories, remains unclear. We report that in mice, hippocampal CA1 neurons show an organized synchronous activity in prelearning home cage sleep that correlates with the learning ensembles only in engram cells, termed preconfigured ensembles. Moreover, after learning, a subset of nonengram cells develops population activity, which is constructed during postlearning offline periods through synaptic depression and scaling, and then emerges to represent engram cells for new learning. Together, our findings indicate that during offline periods there are two parallel processes occurring: conserving of past memories through reactivation, and preparation for upcoming ones through offline synaptic plasticity mechanisms.

neuroscience↗

Florigen-producing cells express FPF1-LIKE PROTEIN 1 that accelerates flowering and stem growth in long days with sunlight red/far-red ratio in Arabidopsis

Seasonal changes in spring induce flowering by expressing the florigen, FLOWERING LOCUS T (FT), in Arabidopsis. FT is expressed in unique phloem companion cells with unknown characteristics. The question of which genes are co-expressed with FT and whether they have roles in flowering remains elusive. Through tissue-specific translatome analysis, we discovered that under long-day conditions with the natural sunlight red/far-red ratio, the FT-producing cells express a gene encoding FPF1-LIKE PROTEIN 1 (FLP1). The master FT regulator, CONSTANS (CO), controls FLP1 expression, suggesting FLP1s involvement in the photoperiod pathway. FLP1 promotes early flowering independently of FT, is active in the shoot apical meristem, and induces the expression of SEPALLATA 3 (SEP3), a key E-class homeotic gene. Unlike FT, FLP1 facilitates inflorescence stem elongation. Our cumulative evidence indicates that FLP1 may act as a mobile signal. Thus, FLP1 orchestrates floral initiation together with FT and promotes inflorescence stem elongation during reproductive transitions.

plant biology↗

Plant Cleavage Factor I complex is essential for precise cleavage and polyadenylation site determination

Cleavage factor I (CFI) is a four-subunit protein complex of the pre-mRNA 3 end processing machinery in eukaryotes. In Arabidopsis, AtCFI25a, AtCFI25b, AtCFI59, and AtCFI68 have been identified as potential components of AtCFI, in silico. Here, we show that the AtCFI25a, AtCFI59, and AtCFI68 proteins each pulled down all components of the CFI, confirming that these subunits form the plant CFI complex. Furthermore, either AtCFI59 or AtCFI68 was essential for nuclear localization of the smallest subunit, AtCFI25a. Mutants with single loss-of-function for AtCFI59 or AtCFI68 showed no obvious morphological defects compared to wild-type plants, while the double mutant displayed pleiotropic morphological defects, identical to those previously reported for AtCFI25a loss-of-function plants. Moreover, these morphological defects correlated with alterations in the usage of 3 UTR cleavage and polyadenylation sites. atcfi25a, atcfi25a atcfi25b and atcfi59 atcfi68 double mutants showed widespread changes in the choice of cleavage and polyadenylation sites. In most cases, more proximal cleavage and polyadenylation sites were used, leading to shorter 3 UTRs. In particular, genes involved in light intensity, light harvesting, photosynthesis and cold responses showed significant dependence on AtCFI function. Furthermore, transcripts coding for AtCFI subunits showed altered 3 end processing in these mutants, suggesting self-regulation function of AtCFI in plants.

molecular biology↗

The pathogenic coronatine toxin hijacks host redox signalling to suppress plant immunity

Reciprocal antagonism between the hormones salicylic acid (SA) and jasmonic acid (JA) is particularly important during infection by the bacterial pathogen Pseudomonas syringae. P. syringae secretion of the virulence-promoting toxin, coronatine, is thought to suppress SA-induced immune responses by manipulating host JA signalling. Here, we report an unexpected JA-independent role of coronatine in promoting pathogen virulence. While JA induced resistance to P. syringae, coronatine promoted pathogen virulence by suppressing cellular accumulation of glutathione, a vital antioxidant required for immunity. Coronatine-mediated suppression of glutathione levels prevented activation of NPR1, a redox-sensitive master regulator of SA-responsive immune genes. Moreover, the accrual of nitric oxide (NO) restored virulence of coronatine-deficient P. syringae, but was counteracted by expression of the host S-nitrosothiol reductase, Thioredoxin h5. Thus, our findings indicate P. syringae utilises coronatine to suppresses host immunity by precisely manipulating glutathione- and NO-mediated redox signalling networks.

plant biology↗

HOTARU: Automatic sorting system for large scale calcium imaging data

Currently, calcium imaging allows long-term recording of large-scale neuronal activity in diverse states. However, it remains difficult to extract neuronal dynamics from recorded imaging data. In this study, we propose an improved constrained nonnegative matrix factorization (CNMF)-based algorithm and an effective method to extract cell shapes with fewer false positives and false negatives through image processing. We also show that the evaluation metrics obtained during image and signal processing can be combined and used for false-positive cell determination. For the CNMF algorithm, we combined cell-by-cell regularization and baseline shrinkage estimation, which greatly improved its stability and robustness. We applied these methods to real data and confirmed their effectiveness. Our method is simpler and faster, detects more cells with lower firing rates and signal-to-noise ratios, and enhances the quality of the extracted cell signals. These advances can improve the standard of downstream analysis and contribute to progress in neuroscience.

neuroscience↗

The hippocampus as a sorter and reverberatory integrator of sensory inputs

In entorhinal-hippocampal networks, the trisynaptic pathway, including the CA3 recurrent circuit, processes episodes of context and space1-3. Recurrent connectivity can generate reverberatory activity4-6, an intrinsic activity pattern of neurons that occurs after sensory inputs have ceased. However, the role of reverberatory activity in memory encoding remains incompletely understood. Here we demonstrate that in mice, synchrony between conditioned stimulus (CS) and unconditioned stimulus (US)-responsible cells occurs during the reverberatory phase, lasting for approximately 15 s, but not during CS and US inputs, in the CA1 and the reverberation is crucial for the linking of CS and US in the encoding of delay-type cued-fear memory. Retrieval-responsive cells developed primarily during the reverberatory phase. Mutant mice lacking N-methyl-D-aspartate receptors (NRs) in CA3 showed a cued-fear memory impairment and a decrease in synchronized reverberatory activities between CS- and US-responsive CA1 cells. Optogenetic CA3 silencing at the reverberatory phase during learning impaired cued-fear memory. Our findings suggest that reverberation recruits future retrieval-responsive cells via synchrony between CS- and US-responsive cells. The hippocampus uses reverberatory activity to link CS and US inputs, and avoid crosstalk during sensory inputs.

neuroscience↗

Proteasome-associated ubiquitin ligase relays target plant hormone-specific transcriptional activators

The ubiquitin-proteasome system is vital to hormone-mediated developmental and stress responses in plants. Ubiquitin ligases target hormone-specific transcriptional activators (TAs) for degradation, but how TAs are processed by proteasomes remains unknown. We report that in Arabidopsis the salicylic acid-and ethylene-responsive TAs, NPR1 and EIN3, are relayed from pathway-specific ubiquitin ligases to proteasome-associated HECT-type UPL3/4 ligases. Activity and stability of NPR1 was regulated by sequential action of three ubiquitin ligases, including UPL3/4, while proteasome processing of EIN3 required physical handover between ethylene-responsive SCFEBF2 and UPL3/4 ligases. Consequently, UPL3/4 controlled extensive hormone-induced developmental and stress-responsive transcriptional programmes. Thus, our findings identify unknown ubiquitin ligase relays that terminate with proteasome-associated HECT-type ligases, which may be a universal mechanism for processive degradation of proteasome-targeted TAs and other substrates. One-Sentence SummaryTranscriptional activators are targeted by proteasomal ubiquitin ligase relays that control their activity and stability.

plant biology↗

Mechanosensory trichome cells evoke a mechanical stimuli-induced immune response in plants

Perception of pathogen-derived ligands by corresponding host receptors is a pivotal strategy in eukaryotic innate immunity. In plants, this is complemented by circadian anticipation of infection timing, promoting basal resistance even in the absence of pathogen threat. Here, we report that trichomes, hair-like structures on the epidermis, directly sense external mechanical forces caused by raindrops to anticipate waterborne infections in Arabidopsis thaliana. Exposure of leaf surfaces to mechanical stimuli initiates the concentric propagation of intercellular calcium waves away from trichomes to induce defence-related genes. Propagating calcium waves enable effective immunity against pathogenic microbes through the calmodulin-binding transcription activator 3 (CAMTA3) and mitogen-activated protein kinases. We propose a novel layer of plant immunity in which trichomes function as mechanosensory cells to detect potential risks.

plant biology↗

Uncovering long-term existence of a silent short-term memory trace

Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that, STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of a silent STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Calcium imaging revealed hippocampal CA1 reactivations of the STM trace during post-learning sleep. Inhibiting offline CA1 activity, N-methyl-D-aspartate receptor activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis and sleep in storing a silent STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first storage as a silent engram, then transformation into an active state by recurrence within 3 days.

neuroscience↗

Offline knowledge assimilations ensue online obscurity to inspire implicit learning

Passive priming of prior knowledge to assimilate ongoing experiences underlies advanced cognitive processing. However, the necessary neural dynamics of memory assimilation remains elusive. Uninstructed brain could also show boosted creativity, particularly after idling states, yet it remains unclear whether the idling brain can spontaneously spark relevant knowledge assimilations. We established a paradigm that links/separates context-dependent memories according to geometrical similarities. Mice exploring one of four contexts one day before undergoing contextual fear conditioning in a square context showed a gradual fear transfer to pre-exposed geometrically relevant contexts next day, but not after 15 min. Anterior cingulate cortex neurons representing relevant, rather than distinct, memories were significantly co-reactivated during post-conditioning sleep only, before their selective integration next day during testing. Disrupting sleep co-reactivations prevented assimilation while preserving recent memory consolidation. Thus, assimilating pertinent memories during sleep through co-reactivation of their respective engrams represents the neural underpinnings of sleep-triggered implicit cortical learning.

neuroscience↗

SNF1-related protein kinase 2 directly regulate group C Raf-like protein kinases in abscisic acid signaling

ABSTRUCTA phytohormone abscisic acid (ABA) has a major role in abiotic stress responses in plants, and subclass III SNF1-related protein kinase 2 (SnRK2) mediates ABA signaling. In this study, we identified Raf36, a group C Raf-like protein kinase in Arabidopsis, as an interacting protein with SnRK2. A series of reverse genetic and biochemical analyses revealed that Raf36 negatively regulates ABA responses and is directly phosphorylated by SnRK2s. In addition, we found that Raf22, another C-type Raf-like kinase, functions partially redundantly with Raf36 to regulate ABA responses. Comparative phosphoproteomic analysis using Arabidopsis wild-type and raf22raf36-1 plants identified proteins that are phosphorylated downstream of Raf36 and Raf22 in planta. Together, these results reveal a novel subsection of ABA-responsive phosphosignaling pathways branching from SnRK2.

plant biology↗

Automatic sorting system for large calcium imaging data

It has become possible to observe neural activity in freely moving animals via calcium imaging using a microscope, which could not be observed previously. However, it remains difficult to extract the dynamics of nerve cells from the recorded imaging data. In this study, we greatly improved the stability, and robustness of the cell activity estimation method via non-negative matrix decomposition with shrinkage estimation of the baseline. In addition, by improving the initial state of the iterative algorithm using a newly proposed method to extract the shape of the cell via image processing, a solution could be obtained with a small number of iterations. These methods were applied to artificial and real data, and their effectiveness was confirmed.

neuroscience↗