Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1α in schizophrenia.

The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such molecule is neurexin 1α (NRXN1α), a presynaptic cell adhesion molecule. In addition, novel autoantibodies that target the nervous system have been found in patients with encephalitis and neurological disorders.

The subiculum sensitizes retrosplenial cortex layer 2/3 pyramidal neurons.

Key Points: Neurons in the retrosplenial cortex (RSC), a cerebral region that connects synaptically with various brain regions, are known to increase neuronal activity in accordance with hippocampal sharp wave-ripples. Pyramidal cells in granular RSC (gRSC) layer 2/3, but not layer 5, exhibit slowly ramping depolarization and considerably delayed spikes in response to a step-pulse current injection. The latencies of delayed spikes in RSC layer 2/3 pyramidal neurons were shortened by a preceding current injection.

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.

Immature electrophysiological properties of human-induced pluripotent stem cell-derived neurons transplanted into the mouse cortex for 7 weeks.

The transplantation of human-induced pluripotent stem cell (hiPSC)-derived cells has emerged as a potential clinical approach for the treatment of brain diseases. Recent studies with animal disease models have shown that hiPSC-derived neurons transplanted into the brain, especially the nigrostriatal area, could restore degenerated brain functions. Further works are required to test whether hiPSC-derived neurons can also gain functional properties for other cortical areas.

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

　During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial.

Hippocampal ripples down-regulate synapses.

The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects.

cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology.

Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ∼30 s.