Temporal Dynamics of Spontaneous Ca2+ Transients, ERBB4, vGLUT1, GAD1, Connexin, and Pannexin Genes in Early Stages of Human Stem Cell Neurodifferentiation

Spontaneous Ca2+ transients drive stem cell proliferation and neurodifferentiation. Deciphering the relationship between neuronal and glial human genes on one side and spontaneous Ca2+ activity on the other side is essential for our understanding of normal brain development, and for insights into the pathogenesis of neurodegenerative and neurodevelopmental disorders. In the present study, forebrain neurons were derived from human embryonic and induced pluripotent stem cells (hESC-H9 and iPSC-15; 22q11.2 deletion) over a period of 21 days in vitro (DIV). Every 1–2 days, multisite optical imaging technique was applied to detect populations of cells with spontaneous Ca2+ transients. The expression levels of 14 genes of interest were analyzed by quantitative polymerase chain reaction (qPCR) on the same biological samples where physiological recordings were performed. The genes analyzed include: the schizophrenia candidate gene ERBB4, connexin (Cx) genes Cx26, Cx36, Cx43, Cx45, Cx47, pannexin-1 (PNX1), neuronal markers PAX6, vGLUT1, GAD1, TUBB3, glial lineage markers BLBP, GFAP, and housekeeping gene ACTB. We found that Ca2+ signals decrease in amplitude, decrease in duration, and increase in frequency during the first 21 days of human neurodifferentiation. The expression levels of ERBB4, PAX6, GAD1, vGLUT1, BLBP, Cx36, Cx45, and PNX1 were found to be strongly positively correlated with the percentage of cells exhibiting spontaneous Ca2+ transients (“Active Cells”). While expression of BLBP, Cx45, ERBB4, GAD1, PAX6, PNX1, and vGLUT1 were correlated with short-duration and long-amplitude Ca2+ transients, Cx43, TUBB3, and Cx47 were better correlated with long-duration and short-amplitude transients. The expression dynamics of Cx26 was unrelated to any aspect of spontaneous Ca2+ activity. Four genes showed an exponential time course with a distinct onset on a given DIV. The onset of PNX1, ERBB4, and vGLUT1 occurred before, while the onset of Cx36 occurred after the first action potentials were detected in early differentiating human neurons

Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals

Disentangling the sources of ionizing radiation in superconducting qubits

Radioactivity was recently discovered as a source of decoherence and correlated errors for the real-world implementation of superconducting quantum processors. In this work, we measure levels of radioactivity present in a typical laboratory environment (from muons, neutrons, and γ-rays emitted by naturally occurring radioactive isotopes) and in the most commonly used materials for the assembly and operation of state-of-the-art superconducting qubits. We present a GEANT-4 based simulation to predict the rate of impacts and the amount of energy released in a qubit chip from each of the mentioned sources. We finally propose mitigation strategies for the operation of next-generation qubits in a radio-pure environment

Disentangling the sources of ionizing radiation in superconducting qubits

Radioactivity was recently discovered as a source of decoherence and correlated errors for the real-world implementation of superconducting quantum processors. In this work, we measure levels of radioactivity present in a typical laboratory environment (from muons, neutrons, and gamma's emitted by naturally occurring radioactive isotopes) and in the most commonly used materials for the assembly and operation of state-of-the-art superconducting qubits. We develop a GEANT-4 based simulation to predict the rate of impacts and the amount of energy released in a qubit chip from each of the mentioned sources. We finally propose mitigation strategies for the operation of next-generation qubits in a radio-pure environment