Biology subjects

Beyer, S. E.

Publications and source records attributed to Beyer, S. E..

3 recordsLinked to original sources

bioRxiv2025

Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice

Environmental toxicants, such as polychlorinated biphenyls (PCBs), are highly stable synthetic organic compounds that are present in air, water, and soil. PCBs have been identified in post-mortem human brains of individuals with neurodegenerative diseases, indicating a possible link between environmental factors and disease risk. Research has revealed an association between PCB exposure and cognitive decline. Therefore, it is crucial to evaluate how PCB mixtures relevant to humans affect brain function and cognition. To investigate the effects of PCBs on memory and transcriptomic profiles, we exposed adult male C57BL/6J mice orally to a synthetic PCB mixture daily. After seven weeks of exposure, the mice were assessed in a spatial object recognition task (SOR) to evaluate long-term spatial memory. Our findings showed that mice exposed to PCBs exhibited deficits in long-term spatial memory. To examine the molecular effects of PCB on the brain, we used a spatial transcriptomics technique to analyze gene expression changes in five brain regions: the hippocampus, neocortex, thalamus, caudal putamen, and fiber tracts. Our analysis of spatial gene expression revealed the molecular signatures influenced by PCB in these susceptible brain regions of mice. Network analysis suggests that these changes are associated with higher chlorinated PCBs present in the brain. Additionally, we show that PCB exposure disrupts the expression of tight junction proteins, which are crucial for maintaining the integrity of the blood-brain barrier (BBB). Thus, our results offer mechanistic insights into how PCB exposure affects brain function and cognition.

neuroscience↗

bioRxiv2025

Single-cell resolution spatial transcriptomic signature of the retrosplenial cortex during memory consolidation

The retrosplenial cortex (RSC) is a critical brain region activated during spatial memory tasks and plays an underlying role in long-term memory consolidation. The RSC comprises multiple cell types, including different classes of excitatory neurons across laminar layers. These layer-specific cells form the hub of neuronal connection between the RSC and other brain regions, including the hippocampus. Despite the established role of the RSC in spatial memory, the transcriptomic signature of the neuronal sub-types in the RSC during spatial memory consolidation remained elusive. Here we used both unbiased and targeted spatial transcriptomic approaches to illuminate the transcriptional signature of the RSC following a spatial memory task. We found that genes related to transcription regulation, protein folding, and mitogen-activated protein kinase pathways were upregulated in the RSC after spatial learning during an early time window of memory consolidation. Further, cell type and excitatory neuronal layer-specific changes in gene expression were resolved using Xenium spatial transcriptomics. The distinct signatures of memory-responsive genes were observed in excitatory neurons across the laminar layers of the RSC following learning. Finally, we observed that blocking RSC excitatory neurons during the early temporal window after learning using a chemogenetic approach impaired long-term spatial memory. Overall, our results uncover a molecular signature of the RSC after learning and demonstrate the role of RSC excitatory neurons during the early time points of memory consolidation. This study underscores the importance of the learning-induced transcriptional signature of the RSC in long-term spatial memory consolidation and reveals a cell-type specific signature of memory-responsive gene expression.

neuroscience↗

bioRxiv2025

Histone Lysine Crotonylation Regulates Long-Term Memory Storage

Histone post-translational modifications (PTMs), particularly lysine acetylation (Kac), are critical epigenetic regulators of transcriptional programs underlying long-term memory consolidation. Beyond Kac, several other non-acetyl acylations have been identified with the ability to regulate transcription; however, their role in memory consolidation remains unknown. Here, we identify histone lysine crotonylation (Kcr) as a molecular switch for long-term memory and glutamatergic neurotransmission. We find that spatial learning induces distinct spatiotemporal patterns of Kcr across hippocampal subregions, and that Kcr stimulates learning-induced gene expression. Through genetic and pharmacological manipulations, we show that reducing hippocampal Kcr levels impairs memory, while increasing Kcr enhances long-term memory. Single-nuclei transcriptome and chromatin accessibility analyses reveals that Kcr facilitates activation of genes regulating glutamate signaling. Cell-cell communication analysis further infers that Kcr enhancement strengthens glutamatergic signaling within principal hippocampal neurons. Real-time fluorescence imaging with genetically encoded sensors functionally validates our multiomics and computational findings--demonstrating the role of Kcr in regulating presynaptic glutamate release and neuronal activity. In summary, our findings elucidate a novel mechanism underlying long-term memory consolidation and excitatory neurotransmission, linking epigenetic events to synaptic function and behavior.

neuroscience↗