PubMed · 14464980
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C L LI. 1961. Cortical intracellular synaptic potentials.. https://doi.org/10.1002/jcp.1030580206
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DNA packaging into heterochromatin is a fundamental mechanism of transcriptional silencing, yet its role in regulating neural progenitor behavior during brain development remains poorly understood. Trimethylation of histone H3 lysine 9 (H3K9me3), catalyzed by the methyltransferases SETDB1, SUV39H1, and SUV39H2, is a defining feature of heterochromatin, but functional redundancy among these enzymes has obscured their developmental roles. Here, we generated a cortex-specific triple knockout mouse model lacking Setdb1, Suv39h1, and Suv39h2 to directly interrogate H3K9me3 function during corticogenesis. Combined loss of H3K9 methyltransferases caused genome-wide depletion of H3K9me3, disruption of neural progenitor cell-cycle progression, and impaired cortical neurogenesis, resulting in microcephaly. H3K9 methyltransferases preserve neural progenitor identity and function by silencing clustered protocadherins, meiosis-associated genes, and a cell-cycle restraint program through H3K9me3 deposition. Loss of H3K9me3 promoted local chromatin opening and increased transcription factor occupancy, enabling transposable elements to acquire cryptic enhancer activity and modulate proximal gene expression. Together, these findings establish H3K9me3 heterochromatin as an active regulator of neural progenitor dynamics and lineage fidelity, revealing a central epigenetic mechanism that restricts aberrant transcriptional programs to ensure cortical growth.
Functional interaction between cortical areas may involve synchronization of activities, manifest as coherence between EEG signals. However, although EEG-EEG coherence changes when motor tasks are compared to each other or rest, there is little evidence that coherence is modulated within an action. To address this issue we used a bimanual drawer-opening task necessitating asymmetrical hand actions and comprising distinct movement phases. Pronounced modulations in EEG-EEG coherence in the beta band (>12-24 Hz) occurred with movement phase. Differences in coherence due to a switch in role of the hands were mainly observed in the alpha band (8-12 Hz). These findings suggest that inter-regional synchronization changes dynamically across task execution in line with behavioral performance.
OBJECTIVE: To demonstrate noninvasive localization of cognitive cortical areas involved in language processing with magnetoencephalography (MEG) interpreted by multiresolution FOCUSS (MR-FOCUSS), a current density imaging technique. METHOD: MEG data were collected during verb-generation and picture-naming tasks from 18 right-handed control subjects and 24 right-handed patients with epilepsy. RESULTS: The averaged epic data from the verb-generation task, analyzed by MR-FOCUSS, showed initial activation in the left supramarginal gyrus, superior temporal gyrus, and angular gyrus at 239 +/- 31 ms in all subjects, consistent with other language mapping studies. Average amplitude of underlying cortical sources was approximately 452 pAm. The averaged epic data from the picture-naming task, analyzed by MR-FOCUSS, showed activation in the left inferior frontal gyrus (IFG) area starting at 436 +/- 40 ms in all subjects. Average amplitudes of underlying cortical sources were approximately 380 pAm. CONCLUSION: The time course of neuronal language processing can be imaged noninvasively with millisecond resolution by magnetoencephalography using the multiresolution FOCUSS technique.