Publications by authors named "A Tokarska"

6 Publications

[STATE PROCUREMENTS: STUDYING THE IMPLEMENTATION OF NATIONAL POLICIES IN TERMS OF PANDEMIC COVID-19].

Georgian Med News 2021 Mar(312):157-163

3Donetsk Law Institute of the Ministry of Internal Affairs of Ukraine, Kryvyi Rih, Ukraine.

This article aims to analyse the implementation of public procurement procedures in the context of national governments' fight against the COVID-19 pandemic and find solutions for adapting those public procurement procedures that are currently used in the healthcare sector to new challenges. For this above purpose, we have applied both theoretical methods such as analysis, synthesis, generalization, and empirical methods such as observation, etc. The research has yielded the following findings: 1) there are no one-size-fits-all solutions in the national governments' fight against the COVID-19 pandemic through the public procurement mechanism, except that national policies in this field intend to speed up the organisation of the public procurement procedures, which would shorten the time for the delivery of medical goods to healthcare facilities; 2) due to the current emergency conditions caused by the COVID-19 pandemic, public procurements of medical supplies are taking place under the non-competitive procedure, i. e. with direct contracting of a specific vendor, which essentially increases corruption risks and allows for subjective decision making; 3) amid the increased corruption risks, there is a need to assign high priority to strengthening the public control (monitoring), as well as the governmental control over medical procurements; 4) saving of public funds as the underlying principle of some national public procurement systems becomes irrelevant in the face of such threats as the global COVID-19 pandemic; 5) it is quite difficult to speak of another principle - effective use of public funds - because we are now dealing with an emergency and the actors (both the government and the expert community) lack understanding of how things might potentially develop in the future. Thus, the authors offer the following solutions: 1) create temporary specialized bodies, with the cross-agency powers, at the national and regional levels, that would take on such functions as: coordination of procurements; needs analysis of particular areas in medical supplies; management of potential vendors. These measures may help make medical procurements as effective as possible in these current conditions; 2) develop special procedures (mechanisms), by national governments, for conducting checks of public procurements in the healthcare sector that are made as part of the response measures against the COVID-19 pandemic, because those check algorithms that are in place today cannot take into account the realities of this particular emergency situation and the conditions in which those procurements are made.
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March 2021

Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner.

Nat Commun 2020 10 9;11(1):5113. Epub 2020 Oct 9.

Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.

Striatal activity is dynamically modulated by acetylcholine and dopamine, both of which are essential for basal ganglia function. Synchronized pauses in the activity of striatal cholinergic interneurons (ChINs) are correlated with elevated activity of midbrain dopaminergic neurons, whereas synchronous firing of ChINs induces local release of dopamine. The mechanisms underlying ChIN synchronization and its interplay with dopamine release are not fully understood. Here we show that polysynaptic inhibition between ChINs is a robust network motif and instrumental in shaping the network activity of ChINs. Action potentials in ChINs evoke large inhibitory responses in multiple neighboring ChINs, strong enough to suppress their tonic activity. Using a combination of optogenetics and chemogenetics we show the involvement of striatal tyrosine hydroxylase-expressing interneurons in mediating this inhibition. Inhibition between ChINs is attenuated by dopaminergic midbrain afferents acting presynaptically on D2 receptors. Our results present a novel form of interaction between striatal dopamine and acetylcholine dynamics.
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http://dx.doi.org/10.1038/s41467-020-18882-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547109PMC
October 2020

The microcircuits of striatum in silico.

Proc Natl Acad Sci U S A 2020 04 22;117(17):9554-9565. Epub 2020 Apr 22.

Department of Neuroscience, Karolinska Institutet, SE-17165 Stockholm

The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma-dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.
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http://dx.doi.org/10.1073/pnas.2000671117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197017PMC
April 2020

The Fat Mass and Obesity-Associated Protein (FTO) Regulates Locomotor Responses to Novelty via D2R Medium Spiny Neurons.

Cell Rep 2019 06;27(11):3182-3198.e9

Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Land Strasse 1, 85764 Neuherberg, Germany. Electronic address:

Variations in the human FTO gene have been linked to obesity and altered connectivity of the dopaminergic neurocircuitry. Here, we report that fat mass and obesity-associated protein (FTO) in dopamine D2 receptor-expressing medium spiny neurons (D2 MSNs) of mice regulate the excitability of these cells and control their striatopallidal globus pallidus external (GPe) projections. Lack of FTO in D2 MSNs translates into increased locomotor activity to novelty, associated with altered timing behavior, without impairing the ability to control actions or affecting reward-driven and conditioned behavior. Pharmacological manipulations of dopamine D1 receptor (D1R)- or D2R-dependent pathways in these animals reveal altered responses to D1- and D2-MSN-mediated control of motor output. These findings reveal a critical role for FTO to control D2 MSN excitability, their projections to the GPe, and behavioral responses to novelty.
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http://dx.doi.org/10.1016/j.celrep.2019.05.037DOI Listing
June 2019

Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system.

Nat Commun 2018 09 12;9(1):3691. Epub 2018 Sep 12.

Department of Neuroscience, Karolinska Institutet, Biomedicum, Stockholm, 171 77, Sweden.

Spiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the brain, yet the cellular and molecular complexity necessary to decode the various acoustic features in the SG has remained unresolved. Using single-cell RNA sequencing, we identify four types of SG neurons, including three novel subclasses of type I neurons and the type II neurons, and provide a comprehensive genetic framework that define their potential synaptic communication patterns. The connectivity patterns of the three subclasses of type I neurons with inner hair cells and their electrophysiological profiles suggest that they represent the intensity-coding properties of auditory afferents. Moreover, neuron type specification is already established at birth, indicating a neuronal diversification process independent of neuronal activity. Thus, this work provides a transcriptional catalog of neuron types in the cochlea, which serves as a valuable resource for dissecting cell-type-specific functions of dedicated afferents in auditory perception and in hearing disorders.
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http://dx.doi.org/10.1038/s41467-018-06033-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135759PMC
September 2018