IntelliSleepScorer, a Software Package with a Graphic User Interface for Mice Automated Sleep Stage Scoring.

Sleep stage scoring in rodents is the process of identifying the three stages: nonrapid eye movement sleep (NREM), rapid eye movement sleep (REM), and wake. Sleep stage scoring is crucial for studying sleep stage-specific measures and effects. Sleep patterns in rodents differ from those in humans, characterized by shorter episodes of NREM and REM interspaced by waking, and traditional manual sleep stage scoring by human experts is time-consuming.

Electroencephalographic Microstates During Sleep and Wake in Schizophrenia.

Background: Aberrant functional connectivity is a hallmark of schizophrenia. The precise nature and mechanism of dysconnectivity in schizophrenia remains unclear, but evidence suggests that dysconnectivity is different in wake versus sleep. Microstate analysis uses electroencephalography (EEG) to investigate large-scale patterns of coordinated brain activity by clustering EEG data into a small set of recurring spatial patterns, or microstates.

encodes a thermosensitive ankyrin ion channel receptor in a triatomine insect.

As ectotherms, insects need heat-sensitive receptors to monitor environmental temperatures and facilitate thermoregulation. We show that a class of ankyrin transient receptor potential (TRP) channels absent in dipteran genomes, may function as insect heat receptors. In the triatomine bug (order: Hemiptera), a vector of Chagas disease, the channel RpTRPA5B displays a uniquely high thermosensitivity, with biophysical determinants including a large channel activation enthalpy change (72 kcal/mol), a high temperature coefficient (Q = 25), and temperature-induced currents from 53°C to 68°C (T = 58.

Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders.

Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations in GRIN2A are also associated with epilepsy and developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to the same protein can result in diverse clinical phenotypes.

A spectrum of altered non-rapid eye movement sleep in schizophrenia.

Background: Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et.

Heterozygous deletion of the autism-associated gene CHD8 impairs synaptic function through widespread changes in gene expression and chromatin compaction.

Whole-exome sequencing of autism spectrum disorder (ASD) probands and unaffected family members has identified many genes harboring de novo variants suspected to play a causal role in the disorder. Of these, chromodomain helicase DNA-binding protein 8 (CHD8) is the most recurrently mutated. Despite the prevalence of CHD8 mutations, we have little insight into how CHD8 loss affects genome organization or the functional consequences of these molecular alterations in neurons.

A Potential Source of Bias in Group-Level EEG Microstate Analysis.

Microstate analysis is a promising technique for analyzing high-density electroencephalographic data, but there are multiple questions about methodological best practices. Between and within individuals, microstates can differ both in terms of characteristic topographies and temporal dynamics, which leads to analytic challenges as the measurement of microstate dynamics is dependent on assumptions about their topographies. Here we focus on the analysis of group differences, using simulations seeded on real data from healthy control subjects to compare approaches that derive separate sets of maps within subgroups versus a single set of maps applied uniformly to the entire dataset.

Scanning mutagenesis of the voltage-gated sodium channel Na1.2 using base editing.

It is challenging to apply traditional mutational scanning to voltage-gated sodium channels (Nas) and functionally annotate the large number of coding variants in these genes. Using a cytosine base editor and a pooled viability assay, we screen a library of 368 guide RNAs (gRNAs) tiling Na1.2 to identify more than 100 gRNAs that change Na1.

Sources of Variation in the Spectral Slope of the Sleep EEG.

The 1/ spectral slope of the electroencephalogram (EEG) estimated in the γ frequency range has been proposed as an arousal marker that differentiates wake, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Here, we sought to replicate and extend these findings in a large sample, providing a comprehensive characterization of how slope changes with age, sex, and its test-retest reliability as well as potential confounds that could affect the slope estimation. We used 10,255 whole-night polysomnograms (PSGs) from the National Sleep Research Resource (NSRR).

AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology.

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain.

Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward Novel Electroceuticals for Glioblastoma.

Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma membrane could be a successful strategy for targeting glioblastoma overgrowth. We screened 47 compounds and compound combinations, most of which were ion-modulating, at different concentrations in the NG108-15 rodent neuroblastoma/glioma cell line.

Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort.

CACNA1I is implicated in the susceptibility to schizophrenia by large-scale genetic association studies of single nucleotide polymorphisms. However, the channelopathy of CACNA1I in schizophrenia is unknown. CACNA1I encodes CaV3.

Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone.

Background: Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABA) currents. However, we previously demonstrated that an endogenous neuroactive steroid epipregnanolone [(3β,5β)-3-hydroxypregnan-20-one] (EpiP) exerts potent peripheral analgesia and blocks T-type calcium currents while sparing GABA currents in rat sensory neurons. This study seeks to investigate the behavioral effects elicited by systemic administration of EpiP and to characterize its use as an adjuvant agent to commonly used general anesthetics (GAs).

Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity.

Background: Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained.

Results: Analyzing single-cell RNA sequencing from Alzheimer's disease (AD) and Huntington's disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons.

Global genetic deletion of Ca3.3 channels facilitates anaesthetic induction and enhances isoflurane-sparing effects of T-type calcium channel blockers.

We previously documented that the Ca3.3 isoform of T-type calcium channels (T-channels) is inhibited by clinically relevant concentrations of volatile anaesthetics, including isoflurane. However, little is understood about the functional role of Ca3.

Neurogranin, Encoded by the Schizophrenia Risk Gene NRGN, Bidirectionally Modulates Synaptic Plasticity via Calmodulin-Dependent Regulation of the Neuronal Phosphoproteome.

Background: Neurogranin (Ng), encoded by the schizophrenia risk gene NRGN, is a calmodulin-binding protein enriched in the postsynaptic compartments, and its expression is reduced in the postmortem brains of patients with schizophrenia. Experience-dependent translation of Ng is critical for encoding contextual memory, and Ng regulates developmental plasticity in the primary visual cortex during the critical period. However, the overall impact of Ng on the neuronal signaling that regulates synaptic plasticity is unknown.

Selective inhibition of glycogen synthase kinase 3α corrects pathophysiology in a mouse model of fragile X syndrome.

Fragile X syndrome is caused by gene silencing and loss of the encoded fragile X mental retardation protein (FMRP), which binds to mRNA and regulates translation. Studies in the mouse model of fragile X syndrome indicate that aberrant cerebral protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5) signaling contributes to disease pathogenesis, but clinical trials using mGluR5 inhibitors were not successful. Animal studies suggested that treatment with lithium might be an alternative approach.