Alexey Semyanov - Academia.edu (original) (raw)

Papers by Alexey Semyanov

Function

Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we p... more Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca2+) imaging of these two cell types in the somatosensory cortex in head-fixed mice moving on the airlifted platform. Ca2+ activity in astrocytes significantly increased during locomotion from a low quiescence level. Ca2+ signals first appeared in the distal processes and then propagated to astrocytic somata, where it became significantly larger and exhibited oscillatory behaviour. Thus, astrocytic soma operates as both integrator and amplifier of Ca2+ signal. In neurons, Ca2+ activity was pronounced in quiescent periods and further increased during locomotion. Neuronal Ca2+ concentration ([Ca2+]i) rose almost immediately following the onset of locomotion, whereas astrocytic Ca2+ signals lagged by several seconds. Such a long lag suggests that astrocytic [Ca2+]i elevations are unlikely to be triggered by the activity of synapses among local neurons. Ca2+ responses to p...

This is the demo Jupyter notebook and a python script file used to analyse connexin plaques in im... more This is the demo Jupyter notebook and a python script file used to analyse connexin plaques in immunostained images. https://doi.org/10.1038/s41419-020-2406-3

SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain,... more SummaryA high-fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognitive abilities. On the other hand, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. Here we show that exposure of young mice to one month of HFD elevates lipid content and increases the relative amount of reduced cytochromes in astrocytes but not in neurons. Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets. Astrocyte remodeling was associated with an increase in expression of ezrin and with no changes in glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Such physiological (non-reactive) enlargement of astrocytes in the brain active milieu promoted glutamate clearance and long-term potentiation. These changes translated into improved explo...

Pflügers Archiv - European Journal of Physiology, 2020

Astroglia represents a class of heterogeneous, in form and function, cells known as astrocytes, w... more Astroglia represents a class of heterogeneous, in form and function, cells known as astrocytes, which provide for homoeostasis and defence of the central nervous system (CNS). Ageing is associated with morphological and functional remodelling of astrocytes with a prevalence of morphological atrophy and loss of function. In particular ageing is associated with (i) decrease in astroglial synaptic coverage; (ii) deficits in glutamate and potassium clearance; (iii) reduced astroglial synthesis of synaptogenic factors such as cholesterol; (iv) decrease in aquaporin 4 channels in astroglial endfeet with subsequent decline in the glymphatic clearance; (v) decrease in astroglial metabolic support through the lactate shuttle; (vi) decreased adult neurogenesis resulting from diminished proliferative capacity of radial stem astrocytes; (vii) decline in the astroglial-vascular coupling and deficient blood-brain barrier and (viii) decrease in astroglial ability to mount reactive astrogliosis. Decrease in reactive capabilities of astroglia is associated with increase in age-dependent neurodegenerative diseases. Astroglial morphology and function can be influenced and improved by lifestyle interventions such as intellectual engagement, social interactions physical exercise, caloric restriction, and healthy diet. These modifications of lifestyle are paramount for cognitive longevity.

Nature Neuroscience, 2021

International Journal of Neural Systems, 2010

We consider the problem of how to recover the state and parameter values of typical model neurons... more We consider the problem of how to recover the state and parameter values of typical model neurons, such as Hindmarsh-Rose, FitzHugh-Nagumo, Morris-Lecar, from in-vitro measurements of membrane potentials. In control theory, in terms of observer design, model neurons qualify as locally observable. However, unlike most models traditionally addressed in control theory, no parameter-independent diffeomorphism exists, such that the original model equations can be transformed into adaptive canonic observer form. For a large class of model neurons, however, state and parameter reconstruction is possible nevertheless. We propose a method which, subject to mild conditions on the richness of the measured signal, allows model parameters and state variables to be reconstructed up to an equivalence class.

GABAA receptors not only respond to the local release of GABA from presynaptic terminals, but can... more GABAA receptors not only respond to the local release of GABA from presynaptic terminals, but can also mediate a persistent 'tonic current'. This reflects the activation of high-affinity GABAA receptors by ambient GABA concentrations. Tonic GABAA-receptor-mediated ...

Nature Neuroscience, 2003

The normal functioning of the brain depends on a network of GABAergic interneurons, which control... more The normal functioning of the brain depends on a network of GABAergic interneurons, which control the excitability of principal neurons and are responsible for oscillatory behaviors that may be critical for information processing 1. GABA A receptor-mediated signaling underlying these processes can be divided into two components. The first has been termed 'phasic' inhibition because it consists of discrete IPSCs. In some sites, GABA can also spill out of the synapse to activate extrasynaptic GABA receptors 2,3. This form of diffuse signaling gives rise to slower events, albeit still temporally locked to GABA exocytosis from the presynaptic neurons. A second form of GABAergic inhibition consists of continuous receptor activity, and is therefore known as 'tonic' inhibition. It changes only slowly with the ambient neurotransmitter concentration and may be critical for analog information processing. GABA A receptors can also open spontaneously in the absence of agonist, further contributing to tonic inhibition 4. Cerebellar granule cells receive both phasic and tonic GABA A receptor-mediated signaling 5,6. Little, however, is known about tonic inhibition in the hippocampus, in spite of the role of this structure in spatial processing, memory encoding and pathologies such as epilepsy. Dentate granule cells have recently been shown to express a GABA A receptor-mediated tonic current 7-9. Whether such currents occur in the hippocampus proper is less certain 10,11. Although tonic currents have been reported in pyramidal neurons 10 , this may reflect the behavior of GABA A receptors at a relatively early stage of development, when GABA uptake mechanisms are incompletely expressed 12-14. We have therefore examined tonic GABA A receptor-mediated currents in the adult rodent hippocampus. By comparing different cell types, we have attempted to understand its role in neuronal circuit function, an aspect that has hitherto resisted investigation elsewhere in the brain. Here we show that a baseline tonic GABA A receptor-mediated current is present in CA1 interneurons but not in pyramidal cells. This tonic current is clearly separable from (and is much larger

The Journal of Neuroscience, Apr 23, 2020

Synaptic plasticity is triggered by different patterns of network activity. Here, we investigated... more Synaptic plasticity is triggered by different patterns of network activity. Here, we investigated how LTP in CA3-CA1 synapses induced by different stimulation patterns is affected by tonic GABA A conductances in rat hippocampal slices. Spike-timingdependent LTP was induced by pairing Schaffer collateral stimulation with antidromic stimulation of CA1 pyramidal neurons. Theta-burst-induced LTP was induced by theta-burst stimulation of Schaffer collaterals. We mimicked increased tonic GABA A conductance by bath application of 30 lM GABA. Surprisingly, tonic GABA A conductance selectively suppressed theta-burstinduced LTP but not spike-timing-dependent LTP. We combined whole-cell patch-clamp electrophysiology, two-photon Ca 21 imaging, glutamate uncaging, and mathematical modeling to dissect the mechanisms underlying these differential effects of tonic GABA A conductance. We found that Ca 21 transients during pairing of an action potential with an EPSP were less sensitive to tonic GABA A conductance-induced shunting inhibition than Ca 21 transients induced by EPSP burst. Our results may explain how different forms of memory are affected by increasing tonic GABA A conductances under physiological or pathologic conditions, as well as under the influence of substances that target extrasynaptic GABA A receptors (e.g., neurosteroids, sedatives, antiepileptic drugs, and alcohol).

International Journal of Molecular Sciences

Data on the long-term consequences of a single episode of generalized seizures in infants are inc... more Data on the long-term consequences of a single episode of generalized seizures in infants are inconsistent. In this study, we examined the effects of pentylenetetrazole-induced generalized seizures in three-week-old rats. One month after the seizures, we detected a moderate neuronal loss in several hippocampal regions: CA1, CA3, and hilus, but not in the dentate gyrus. In addition, long-term synaptic potentiation (LTP) was impaired. We also found that the mechanism of plasticity induction was altered: additional activation of metabotropic glutamate receptors (mGluR1) is required for LTP induction in experimental rats. This disturbance of the plasticity induction mechanism is likely due to the greater involvement of perisynaptic NMDA receptors compared to receptors located in the core part of the postsynaptic density. This hypothesis is supported by experiments with selective blockades of core-located NMDA receptors by the use-dependent blocker MK-801. MK-801 had no effect on LTP ind...

Signal Transduction and Targeted Therapy

Opera medica et physiologica, Jun 30, 2016

The name astroglia unifies many non-excitable neural cells that act as primary homeostatic cells ... more The name astroglia unifies many non-excitable neural cells that act as primary homeostatic cells in the nervous system. Neuronal activity triggers multiple homeostatic responses of astroglia that include increase in metabolic activity and synthesis of neuronal preferred energy substrate lactate, clearance of neurotransmitters and buffering of extracellular K+ ions to name but a few. Many (if not all) of astroglial homeostatic responses are controlled by dynamic changes in the cytoplasmic concentration of two cations, Ca2+ and Na+. Intracellular concentration of these ions is tightly controlled by several transporters and can be rapidly affected by activation of respective fluxes through ionic channels or ion exchangers. Here we provide a comprehensive review of astroglial Ca2+ and Na+ signalling.

Signal Transduction and Targeted Therapy, 2021

Purinergic Signalling, 2021

Purinergic signaling plays a pivotal role in physiological processes and pathological conditions.... more Purinergic signaling plays a pivotal role in physiological processes and pathological conditions. Over the past decades, conventional pharmacological, biochemical, and molecular biology techniques have been utilized to investigate purinergic signaling cascades. However, none of them is capable of spatially and temporally manipulating purinergic signaling cascades. Currently, optical approaches, including optopharmacology and optogenetic, enable controlling purinergic signaling with low invasiveness and high spatiotemporal precision. In this mini-review, we discuss optical approaches for controlling purinergic signaling and their applications in basic and translational science.

Trends in Neurosciences, 2021

We define a new concept of 'active milieu' that unifies all components of nervous tissue (neurona... more We define a new concept of 'active milieu' that unifies all components of nervous tissue (neuronal and glial compartments, extracellular space, extracellular matrix and vasculature) into a dynamic information processing system. Within this framework, we focus on the role of astrocytic processes, classified into organelle-containing branches and organelle-free leaflets. Astrocytic branches with emanating leaflets are homologous to dendritic shafts with spines. Within the active milieu, astrocytic processes are engaged in reciprocal interactions with neuronal compartments and communication with other cellular and non-cellular elements of the nervous tissue.