Biology subjects

Aleshin, S.

Publications and source records attributed to Aleshin, S..

4 recordsLinked to original sources

bioRxiv2025

Short Polysialic Acid Counteracts Age-Related Synaptic and Cognitive Deficits

Impaired activity of glutamate transporters, elevated concentration of extrasynaptic glutamate and hyperactivity of extrasynaptic GluN2B-containing NMDA receptors are common features in aging and several neurological conditions, including Alzheimers disease (AD). Previous studies revealed that polysialic acid (polySia), a glycan predominantly carried by the neural cell adhesion molecule NCAM, inhibits extrasynaptic NMDA receptors and supports synaptic plasticity in healthy adult brains. Moreover, intranasal delivery of polySia with the degree of polymerization 12 (NANA12) rescued synaptic plasticity and cognitive functions in models of tauopathy and amyloidosis associated with AD. Here, we comparatively studied the effects of NANA12 in young (4 months) old (26 months) and very old (29 months) mice. Strikingly, NANA12 promoted cognitive flexibility in attentional set-shifting (ASST) tests and spatial memory in the Barnes maze in very old mice. To capture fine-grained effects undetectable by conventional methods, we introduced a novel trial-wise data analysis approach for evaluating ASST performance. The observed cognitive improvements were not due to changes in the size of hippocampal memory engrams, visualized by c-Fos immunolabeling after reactivation of spatial memory in the probe trial. Five-day treatment with NANA12 did not affect neuronal structure (MAP2 levels), expression of senescence (lipofuscin) or neuroinflammation (microglial Iba1) markers, activation of BDNF receptors (p-TrkB) or expression of endogenous polySia in the hippocampus of very old mice. However, cognitive improvements correlated with the normalized size of CD68+ microglial lysosomes and reduced amounts of pre- and postsynaptic proteins at these structures. Thus, our data demonstrate the potential of short polySia to reduce synaptic phagocytosis and restore key cognitive functions attenuated in aging.

neuroscience↗

bioRxiv2024

Neurocan regulates axon initial segment organization and neuronal activity in cultured cortical neurons

The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, nodes of Ranvier and the AIS, highlighting its potential role in regulation of axonal excitability. Here, we used knockdown and knockout approaches in mouse primary cortical neurons in combination with immunocytochemistry, western blotting and electrophysiological techniques to characterize the role of Ncan in the organization of PNNs and AIS and in the regulation of neuronal activity. We found that reduced Ncan levels led to remodeling of PNNs around neurons via upregulated Aggrecan mRNA and protein levels, increased expression of activity-dependent c-Fos and FosB genes and elevated spontaneous synaptic activity. The latter correlated with increased levels of Ankyrin-G in the AIS particularly in excitatory neurons, and with the elevated expression of Nav1.6 channels. Our results suggest that Ncan regulate expression of key proteins in PNNs and AISs and provide new insights into its role in the fine-tuning of neuronal functions.

neuroscience↗

bioRxiv2021

Alternative female and male developmental strategies in the dynamic balance of human visual perception

The numerous multistable phenomena in vision, hearing and touch attest that the inner workings of perception are prone to instability. We investigated a visual example - binocular rivalry - with an accurate no-report paradigm, and uncovered developmental and maturational lifespan trajectories that were specific for age and sex. To interpret these trajectories, we hypothesized that conflicting objectives of visual perception - such as stability of appearance, sensitivity to visual detail, and exploration of fundamental alternatives - change in relative importance over the lifespan. Computational modelling of our empirical results allowed us to estimate this putative development of stability, sensitivity, and exploration over the lifespan. Our results confirmed prior findings of developmental psychology and appear to quantify important aspects of neurocognitive phenotype. Additionally, we report atypical function of binocular rivalry in autism spectrum disorder and borderline personality disorder. Our computational approach offers new ways of quantifying neurocognitive phenotypes both in development and in dysfunction.

neuroscience↗

bioRxiv2020

Instability with a purpose: how the visual brain makes decisions in a volatile world

In ambiguous or conflicting sensory situations, perception is often multistable in that it changes abruptly at irregular intervals, shifting perpetually between distinct alternatives. Intriguingly, the interval statistics of these alternations exhibits quasi-universal characteristics, suggesting a general mechanism. Here we show that the stereotypical features of multistable perception, exemplified by binocular rivalry, are reproduced in detail by a hierarchical dynamics operating out of equilibrium. Its constitutive elements are discretely stochastic and idealize the metastability of cortical networks. Independent elements accumulate visual evidence at one level, while groups of coupled elements compete for dominance at another level. As soon as one group dominates perception, feedback inhibition suppresses supporting evidence. This mechanism is corroborated compellingly by unexpected serial dependencies of perceptual alternations. Moreover, it satisfies normative constraints of continuous decision-making. We conclude that multistable perception reflects decision-making in a volatile world: integrating evidence over space and time, choosing categorically between hypotheses, while concurrently evaluating alternatives.

neuroscience↗