Biology subjects

Yamada, R. G.

Publications and source records attributed to Yamada, R. G..

5 recordsLinked to original sources

bioRxiv2024

Boundary conditions for synaptic homeodynamics during the sleep-wake cycle

Understanding synaptic dynamics during the sleep-wake cycle is crucial yet remains controversial. The synaptic homeostasis hypothesis (SHY) suggests synaptic depression during non-rapid eye movement (NREM) sleep, while other studies report synaptic potentiation or synaptic changes during NREM sleep depending on activities in wakefulness. To find boundary conditions between these contradictory observations, we focused on learning rules and firing patterns that contribute to the synaptic dynamics. Using computational models, we found that under Hebbian and spike-timing dependent plasticity (STDP), wake-like firing patterns decrease synaptic weights, while sleep-like patterns strengthen synaptic weights. We refer to this tendency as Wake Inhibition and Sleep Excitation (WISE). Conversely, under Anti-Hebbian and Anti-STDP, synaptic depression during NREM sleep was observed, aligning with the conventional synaptic homeostasis hypothesis. Moreover, synaptic changes depended on firing rate differences between NREM sleep and wakefulness. We provide a unified framework that could explain synaptic homeodynamics under the sleep-wake cycle.

neuroscience↗

bioRxiv2023

Post-synaptic competition between calcineurin and PKA regulates mammalian sleep-wake cycles

Phosphorylation of synaptic proteins is a pivotal biochemical reaction that controls the sleep-wake cycle in mammals. Protein phosphorylation in vivo is reversibly regulated by kinases and phosphatases. In this study, we investigated a pair of kinases and phosphatases that reciprocally regulate sleep duration. Through comprehensive screening of Protein kinase A (PKA) and phosphoprotein phosphatase (PPP) family genes via the generation of 40 gene knockout mouse lines including post-natal CRISPR targeting, we identified a regulatory subunit of PKA (Prkar2b), a regulatory subunit of protein phosphatase (PP) 1 (Pppr1r9b), and catalytic and regulatory subunits of PP2B (calcineurin) (Ppp3ca and Ppp3r1) as sleep control genes. AAV-mediated stimulation of PKA and PP1/calcineurin activities confirmed PKA as a wake-promoting kinase, while PP1 and calcineurin function as sleep-promoting phosphatases. The importance of these phosphatases in sleep regulation is supported by the dramatic changes in sleep duration associated with their increased and decreased activity, ranging from approximately 17.3 hours/day (PP1 expression) to 6.7 hours/day (post-natal CRISPR targeting of calcineurin). For these phosphatases to exert their sleep-promoting effects, localization signals to the excitatory post-synapse were necessary. Furthermore, the wake-promoting effect of PKA localized to the excitatory post-synapse negated the sleep-promoting effect of calcineurin, suggesting that PKA and calcineurin construct a hierarchical phosphorylation control network for sleep regulation at excitatory post-synapses.

neuroscience↗

bioRxiv2023

Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. We show here that CaMKII-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in sleep homeostasis regulation. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. We propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

neuroscience↗

bioRxiv2021

Realization of phosphorylation hypothesis of sleep by mammalian CaMKIIβ

The reduced sleep duration observed in Camk2a and Camk2b knockout mice revealed the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CAMKII{beta} as sleep-promoting kinases and lead to the phosphorylation hypothesis of sleep. However, the underlying mechanism of sleep regulation by kinases and protein phosphorylation is largely unknown. Here, we demonstrate that the phosphorylation states of CaMKII{beta} regulates sleep duration and sleep needs. Importantly, the activation or inhibition of CaMKII{beta} can increase or decrease sleep duration by almost two-fold, supporting the role of CaMKII{beta} as a core sleep regulator in mammals. This sleep regulation depends on the kinase activity of CaMKII{beta} in excitatory neurons. Furthermore, CaMKII{beta} mutants mimicking different phosphorylation states can regulate various sleep steps including sleep induction, sleep maintenance, and sleep cancelation. Key CaMKII{beta} residues responsible for the mode switch undergo ordered (auto-)phosphorylation. We thus propose that ordered multi-site phosphorylation of CaMKII{beta} underlies multi-step sleep regulation in mammals.

neuroscience↗

bioRxiv2020

CUBIC-Cloud: An Integrative Computational Framework Towards Community-Driven Whole-Mouse-Brain Mapping

Recent advancements in tissue clearing technologies have offered unparalleled opportunities for researchers to explore the whole mouse brain at cellular resolution. With the expansion of this experimental technique, however, a scalable and easy-to-use computational tool is in demand to effectively analyze and integrate whole-brain mapping datasets. To that end, here we present CUBIC-Cloud, a cloud-based framework to quantify, visualize and integrate whole mouse brain data. CUBIC-Cloud is a fully automated system where users can upload their whole-brain data, run analysis and publish the results. We demonstrate the generality of CUBIC-Cloud by a variety of applications. First, we investigated brain-wide distribution of PV, Sst, ChAT, Th and Iba1 expressing cells. Second, A{beta} plaque deposition in AD model mouse brains were quantified. Third, we reconstructed neuronal activity profile under LPS-induced inflammation by c-Fos immunostaining. Last, we show brain-wide connectivity mapping by pseudo-typed Rabies virus. Together, CUBIC-Cloud provides an integrative platform to advance scalable and collaborative whole-brain mapping.

neuroscience↗