Biology subjects

Samokhina, E.

Publications and source records attributed to Samokhina, E..

2 recordsLinked to original sources

bioRxiv2025

Tau controls NMDA receptor trafficking during homeostatic synaptic plasticity

Homeostatic synaptic plasticity is essential for maintaining stable neural circuit function by preventing excessive neuronal excitation or inhibition. Chronic perturbation of neuronal activity triggers a compensatory modulation of the number of -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors at the excitatory synapses. Previous research has primarily focused on AMPA receptors, yet the molecular mechanisms regulating the trafficking of NMDA receptors during homeostatic synaptic scaling remain unclear. Here we identify the microtubule-associated protein Tau as an essential molecule that mediates the synaptic upscaling of GluN2B-containing NMDA receptors during prolonged synaptic inactivity. Chronic activity blockade increases Tau phosphorylation at Ser-235 by cyclin-dependent kinase 5 (Cdk5), enhancing its interaction with and retention of active Fyn tyrosine kinase in the postsynaptic compartment. This promotes the phosphorylation of GluN2B at Tyr-1472, subsequently stabilising the expression of NMDA receptors on the neuronal plasma membrane. Finally, we showed that Tau pathology and disease-associated mutations in Tau and the GluN2B carboxyl-terminal tail disrupt the homeostatic synaptic upscaling of NMDA receptors following chronic neuronal silencing. Together, our findings identify a physiological role for Tau in homeostatic synaptic plasticity, the perturbation of which can lead to neuronal hyperexcitation, seizures and excitotoxic cell death.

neuroscience↗

bioRxiv2024

Potassium homeostasis during disease progression of Alzheimers Disease

Alzheimers disease (AD) is an age-dependent neurodegenerative disorder characterized by neuronal loss leading to dementia and ultimately death. Whilst the loss of neurons is central to the disease, it is becoming clear that glia, specifically astrocytes, contribute to the onset and progression of neurodegeneration. Astrocytic role in retaining ion homeostasis in the extracellular milieu is fundamental for multiple brain functions, including synaptic plasticity and neuronal excitability, which are compromised during AD and affect neuronal signalling. In this study, we have measured the astrocytic K+ clearance rate in the hippocampus and somatosensory cortex of a mouse model for AD during disease progression. Our results establish that astrocytic [K+]o clearance in the hippocampus is reduced in symptomatic 5xFAD mice, and this decrease is region-specific. The decrease in the [K+]o clearance rate correlated with a significant reduction in the expression and conductivity of Kir4.1 channels and a decline in the number of primary connected astrocytes. Moreover, astrocytes in the hippocampus of symptomatic 5xFAD mice demonstrated increased reactivity which was accompanied by an increased excitability and altered spiking profile of nearby neurons. These findings indicate that the supportive function astrocytes typically provide to nearby neurons is diminished during disease progression, which affects the neuronal circuit signalling in this area and provides a potential explanation for the increased vulnerability of neurons in AD.

neuroscience↗