Machine-learning-based quality control of contractility of cultured human-induced pluripotent stem-cell-derived cardiomyocytes.

The precise and early assessment of cardiotoxicity is fundamental to bring forward novel drug candidates to the pharmaceutical market and to avoid their withdrawal from the market. Recent preclinical studies have attempted to use human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) to predict clinical cardiotoxicity, but the heterogeneity and inconsistency in the functional qualities of the spontaneous contractility of hiPSC-CMs across cell culture wells and product lots still matter. To rapidly assess the functional qualities of hiPSC-CMs without histological labeling, we optically detected the contractility of confluently cultured hiPSC-CMs using bright-field microscopy. Using a method that consisted of data preprocessing, data augmentation, dimensionality reduction, and supervised learning, we succeeded in precisely discriminating between functionally normal and abnormal contractions of hiPSC-CMs.

Maternal Immune Activation in Pregnant Mice Produces Offspring with Altered Hippocampal Ripples.

Psychiatric disorders, such as schizophrenia and autism spectrum disorder, are associated with sleep disturbances and deficits in memory consolidation; however, the relationship between these symptoms remains unclear. Here, we focused on hippocampal sharp-wave ripples (SWRs), a form of transient high-frequency oscillations that occur during sleep and behavioral immobility and contribute to memory consolidation. We activated the maternal immune system with polyinosinic-polycytidylic acid (poly(I : C)), one of the major pharmacological models of psychiatric disorders, to investigate whether SWR activity is altered in acute slices of the hippocampus from offspring born to poly(I : C)-treated mouse dams. Using robust continuous clustering in a low dimensional space defined by a uniform manifold approximation and projection, we found that mice with prenatal exposure to poly(I : C) exhibited different feature distributions of SWR waveforms without affecting the overall frequencies of SWR events. Based on our results, maternal immune activation leads to altered SWR patterns in offspring.

Deep learning-based quality control of cultured human-induced pluripotent stem cell-derived cardiomyocytes.

Using bright-field images of cultured human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we trained a convolutional neural network (CNN), a machine learning technique, to decide whether the qualities of cell cultures are suitable for experiments. VGG16, an open-source CNN framework, resulted in a mean F1 score of 0.89 and judged the cell qualities at a speed of approximately 2000 images per second when run on a commercially available laptop computer equipped with Core i7. Thus, CNNs provide a useful platform for the high-throughput quality control of hiPSC-CMs.

Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrams.