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Biology subjects

Rom, A.

Publications and source records attributed to Rom, A..

2 recordsLinked to original sources

Travelling waves or sequentially activated discrete modules: mapping the granularity of cortical propagation

Numerous studies have identified travelling waves in the cortex and suggested they play important roles in brain processing. These waves are most often measured using macroscopic methods that are unable to assess the local spiking activity underlying wave dynamics. Here we investigated the possibility that waves may not be travelling at the single neuron scale. We first show that sequentially activating two discrete brain areas can appear as travelling waves in EEG simulations. We next reproduce these results using an analytical model of two sequentially activated regions. Using this model, we were able to generate wave-like activity with variable directions, velocities, and spatial patterns, and to map the discriminability limits between travelling waves and modular sequential activations. Finally, we investigated the link between field potentials and single neuron excitability using large-scale measurements from turtle cortex ex-vivo. We found that while field potentials exhibit wave-like dynamics, the underlying spiking activity was better described by consecutively activated spatially adjacent groups of neurons. Taken together, this study suggests caution when interpreting phase delay measurements as continuously propagating wavefronts in two different spatial scales. A careful distinction between modular and wave excitability profiles across scales will be critical for understanding the nature of cortical computations.

neuroscience↗

Regulation of CHD2 expression by the Chaserr long noncoding RNA is essential for viability

Genomic loci adjacent to genes encoding for transcription factors and chromatin remodelers are enriched for long non-coding RNAs (lncRNAs), but the functional importance of this enrichment is largely unclear. Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller with various reported functions in cell differentiation and DNA damage response. Heterozygous mutations in human CHD2 have been implicated in epilepsy, neurodevelopmental delay, and intellectual disability. Here we show that Chaserr, a highly conserved lncRNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to increased transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potentially viable strategy for increasing CHD2 levels in haploinsufficient individuals.

molecular biology↗