Borodinova, A. A. | bioRxiv Science

bioRxiv2025

EPIGENETIC REPROGRAMMING OF CELL IDENTITY IN THE RAT PRIMARY NEURON-GLIA CULTURES INVOLVES HISTONE SEROTONYLATION

Epigenetic rearrangements can create a favorable environment for the intrinsic plasticity of brain cells, leading to cellular reprogramming into virtually any cell type through the induction of cell-specific transcriptional programs. In this study, we assessed how chromatin remodeling induced by broad-spectrum HDAC inhibitors affects cellular differentiation trajectories in rat primary neuron-glia cultures using a combination of transcriptomics, qPCR and cytochemistry. We described epigenetic regulation of transcriptional programs controlled by master transcription factors and neurotrophins in the context of neuronal and glial differentiation and evaluated the expression of representative cell-specific markers. The results obtained suggest that HDAC inhibitors reduce proliferative potential of cultured cells and induce transcriptomic changes associated with cell differentiation and specialization. Particularly, we revealed a significant upregulation of genes typically expressed in neuromodulatory neurons, and downregulation of genes expressed in glia and inhibitory neurons. Transcriptional changes were accompanied by continuous elevation of histone serotonylation levels in both neurons and glia. We assume that early appearance of the enhanced histone serotonylation marks, and the persistence of these changes over many hours in distinct brain cells may indicate that chromatin remodeling induced by histone serotonylation contributes to the maintainance of a new transcriptional programs associated with cellular reprogramming.

neuroscience↗

bioRxiv2023

PLASTICITY OF RESPONSE PROPERTIES OF MOUSE VISUAL CORTEX NEURONS INDUCED BY OPTOGENETIC TETANIZATION IN VIVO

Heterosynaptic plasticity, along with Hebbian homosynaptic plasticity, is an important mechanism ensuring stable operation of learning neuronal networks. However, whether heterosynaptic plasticity occurs in the whole brain in vivo, and what role(s) in brain function in vivo it could play, remains unclear. Here, we used an optogenetics approach to apply a model of intracellular tetanization, which was established and employed to study heterosynaptic plasticity in brain slices, to study plasticity of response properties of neurons in mouse visual cortex in vivo. We show that optogenetically evoked high-frequency bursts of action potentials (optogenetic tetanization) in principal neurons of the visual cortex induce long-term changes of responses to visual stimuli. Optogenetic tetanization had distinct effects on responses to different stimuli: responses to optimal and orthogonal orientations decreased, response to null direction did not change, and responses to oblique orientations increased. As a result, direction selectivity of the neurons decreased, and orientation tuning became broader. Since optogenetic tetanization was a purely postsynaptic protocol, applied in the absence of sensory stimulation, and thus without association of presynaptic activity with bursts of action potentials, the observed changes were mediated by mechanisms of heterosynaptic plasticity. We conclude that heterosynaptic plasticity can be induced in vivo and propose that it may play important homeostatic roles in operation of neural networks by helping to prevent runaway dynamics of responses to visual stimuli and to keep the tuning of neuronal responses within the range optimized for encoding of multiple features in population activity.

neuroscience↗