Biology subjects

Dembrow, N.

Publications and source records attributed to Dembrow, N..

3 recordsLinked to original sources

bioRxiv2025

Convergent Control of NREM Sleep and Anesthesia by Prefrontal Layer 5 Extratelencephalic Neurons

The cortical mechanisms that actively suppress consciousness remain poorly understood. Here, we identify a specific subset of prefrontal cortical (PFC) neurons that are activated under anesthesia while most cortical neurons are suppressed. Chemogenetic activation of these excitatory neurons enhances anesthetic potency and deepens NREM sleep, whereas their inhibition blunts anesthetic effects and disrupts sleep. We designate these cells NREM- and Anesthesia-Promoting (NAP) neurons. NAP neurons correspond to layer 5 extratelencephalic (L5 ET) neurons enriched in hyperpolarization-activated cyclic nucleotide-gated (HCN1) expression and characteristic HCN-mediated electrophysiological properties. Mechanistically distinct anesthetics act directly and specifically on PFC L5-ET neurons to increase their excitability. NAPs have sparse cortical projections and predominately innervate subcortical targets including anterior and reticular thalamic nuclei. Using a transgenic mouse line (Colgalt2-cre), we confirm that PFC L5 ET neurons are preferentially activated under anesthesia and during deep recovery NREM sleep. Finally, we show that activation of thalamic-projecting Colgalt2-expressing PFC neurons is sufficient to promote deep NREM sleep. These findings identify a novel prefrontal corticothalamic circuit that provides a shared cortical substrate for naturally occurring sleep and anesthetic-induced unconsciousness.

neuroscience↗

bioRxiv2023

Expansion-assisted selective plane illumination microscopy for nanoscale imaging ofcentimeter-scale tissues

Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure of cells and tissues at sub-diffraction resolutions and near single molecule sensitivity, driving discoveries in diverse fields of biology, including neuroscience. Biological tissue is organized over scales of nanometers to centimeters. Harnessing molecular imaging across intact, three-dimensional samples on this scale requires new types of microscopes with larger fields of view and working distance, as well as higher throughput. We present a new expansion-assisted selective plane illumination microscope (ExA-SPIM) with aberration-free 1.5 {micro}mx1.5 {micro}mx3 {micro}m optical resolution over a large field of view (10.6x8.0 mm2) and working distance (35 mm) at speeds up to 946 megavoxels/sec. Combined with new tissue clearing and expansion methods, the microscope allows imaging centimeter-scale samples with 375 nm lateral and 750 nm axial resolution (4x expansion), including entire mouse brains, with high contrast and without sectioning. We illustrate ExA-SPIM by reconstructing individual neurons across the mouse brain, imaging cortico-spinal neurons in the macaque motor cortex, and visualizing axons in human white matter.

neuroscience↗

bioRxiv2020

Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse

The primary motor cortex (M1) is essential for voluntary fine motor control and is functionally conserved across mammals. Using high-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, and mouse, we demonstrate a broadly conserved cellular makeup of this region, whose similarity mirrors evolutionary distance and is consistent between the transcriptome and epigenome. The core conserved molecular identity of neuronal and non-neuronal types allowed the generation of a cross-species consensus cell type classification and inference of conserved cell type properties across species. Despite overall conservation, many species specializations were apparent, including differences in cell type proportions, gene expression, DNA methylation, and chromatin state. Few cell type marker genes were conserved across species, providing a short list of candidate genes and regulatory mechanisms responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allowed the Patch-seq identification of layer 5 (L5) corticospinal Betz cells in non-human primate and human and characterization of their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell type diversity in M1 across mammals and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

neuroscience↗