Biology subjects

Cembrowski, M. S.

Publications and source records attributed to Cembrowski, M. S..

5 recordsLinked to original sources

bioRxiv2024

Neuronal heterogeneity in the medial septum and diagonal band of Broca: classes and continua

The medial septum and diagonal band of Broca (MSDB) is known for its diverse populations of cholinergic, GABAergic, and glutamatergic neurons, each contributing to various cognitive processes. However, cell-specific manipulations within this region often result in incongruous behavioral outcomes and reach conflicting conclusions, likely because of a hitherto unknown molecular complexity in its cellular landscape. In this study, we employed single-cell RNA sequencing to thoroughly describe the heterogeneity of MSDB neurons. We confirmed previously established neuronal classes, found gene expression gradients within them and revealed genetically defined subclusters. Moreover, we characterized the genetic profiles of these neuronal subclusters and mapped their spatial distribution. Our analysis presents a comprehensive description of the heterogeneity of MSDB neurons, provides marker genes to target them, explains previous paradoxical results, and opens unexplored avenues to study the impact of neuromodulators in the basal forebrain.

neuroscience↗

bioRxiv2023

Leveraging the power of 3D brain-wide imaging and mapping tools for brain injury research in murine models

Despite the fundamental importance of understanding impaired brain activity exhibited in post-traumatic epilepsy and other neurological impairments associated with traumatic brain injury (TBI), knowledge of how brain injury affects neuronal activity remains remarkably incomplete. We describe a whole-brain imaging and analysis approach to identify alterations in neuronal activity after TBI as a complementary method to conventional two-dimensional (2D) histological approaches. Here we report an easy-to-follow experimental pipeline to quantify changes in the whole mouse brain using tissue clearing, light sheet microscopy (LSM) and an optimised open-access atlas registration workflow. We validated the outcome of the pipeline using high throughput image analysis software and a secondary atlas registration method. Using the CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) TBI model, TRAP2 mice were subjected to repeated mild TBI or sham treatment followed by tamoxifen injection to lock c-Fos activity after TBI. Brains were SHIELD fixed and passively cleared for imaging of c-Fos+ cells throughout the rostro-caudal axis of the brain using a light sheet microscope equipped with a specialized whole-brain imaging chamber. Volumetric images were stitched and 3D rendered using Arivis Vision4D image analysis software. For quantitative analysis, 2D image stacks were exported to segment c-Fos+ cells and register them to the Allen Mouse Brain Atlas using the BrainQuant3D python package. As a result, c-Fos+ cell counts were estimated throughout the brain and heatmaps were generated. We identified a brain-wide reduction in c-Fos cell density in the TBI group compared to sham controls, indicative of TBI-induced changes in whole brain neuronal activity. Further studies using multi-dimensional imaging coupled with analysis tools will deepen our understanding of post-TBI brain-wide dynamics.

neuroscience↗

bioRxiv2022

Sharp cell-type-identity changes differentiate the retrosplenial cortex from the neocortex

The laminae of the neocortex are fundamental processing layers of the mammalian brain. Notably, such laminae are believed to be relatively stereotyped across short spatial scales, such that shared laminae between nearby brain regions exhibit similar constituent cells. Here, we considered a potential exception to this rule by studying the retrosplenial cortex (RSC), a brain region known for sharp cytoarchitectonic differences across its granular-dysgranular border. Using a variety of transcriptomics techniques, we identified, spatially mapped, and interpreted the excitatory cell-type landscape of the mouse RSC. In doing so, we surprisingly uncovered that RSC gene expression and cell types change sharply at the granular-dysgranular border. Additionally, supposedly homologous laminae between the RSC and neocortex are effectively wholly distinct in their cell-type composition. In collection, the RSC exhibits a variety of intrinsic cell-type specializations, and embodies a new neocortical organizational principle wherein cell-type identities vary sharply within and between brain regions.

neuroscience↗

bioRxiv2021

Spatially patterned excitatory neuron subtypes and circuits within the claustrum

The claustrum is a functionally and structurally complex brain region, whose very spatial extent remains debated. Histochemical-based approaches typically treat the claustrum as a relatively narrow region that primarily projects to the neocortex, whereas circuit-based approaches suggest a broader region embedding neocortical and other neural circuits. Here, we took a bottom-up, cell-type-specific approach to complement and possibly unite these seemingly disparate conclusions. Using single-cell RNA-sequencing, we found that the claustrum is comprised of two excitatory neuron subtypes that are differentiable from the surrounding cortex. Multicolor retrograde tracing in conjunction with 12-channel multiplexed in situ hybridization revealed a core-shell spatial arrangement of these subtypes, as well as differential projection targets. Thus, the claustrum is comprised of excitatory neuron subtypes with distinct molecular and circuit properties, whose spatial patterns reflect the narrower and broader claustral extents debated in previous research. This subtype-specific heterogeneity likely shapes the functional complexity of the claustrum.

neuroscience↗

bioRxiv2019

A sparse, spatially biased subtype of mature granule cell is preferentially recruited in hippocampal-associated behaviors

Animals can store information about experiences by activating specific neuronal populations, and subsequent reactivation of these neural ensembles can lead to recall of salient experiences. In the hippocampus, granule cells of the dentate gyrus participate in such memory engrams; however, whether there is an underlying logic to granule cell participation has not been examined. Here, we found that a broad range of novel experiences preferentially activates granule cells of the suprapyramidal blade relative to the infrapyramidal blade. Motivated by this, we identified a suprapyramidal-blade-enriched population of granule cells with distinct spatial, morphological, physiological, and developmental properties. Via transcriptomics, we mapped these traits onto a sparse and discrete granule cell subtype that was recruited at a ten-fold greater frequency than expected by subtype prevalence, constituting the majority of all recruited granule cells. Thus, a rare and spatially localized granule cell subtype is intrinsically predisposed to activation during hippocampal memory formation.

neuroscience↗