Opera Medica et Physiologica

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Printed March 30, 2019;
Published ahead of print March 29, 2019; Printed March 30, 2019; OM&P 2019 Volume 5 Issue 1, pages 7-16; doi:10.20388/omp2019.001.0063
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Computational models for two neuron/astrocyte networks are developed to explore mechanisms underlying the astrocytes’ role in maintaining neuronal firing patterns. For the first network, a single neuron receives periodic excitatory inputs at varying frequencies. We consider the role played by several astrocytic dendritic processes, including the Na+-K+ ATPase pump, K+  channels and gap junctions in maintaining extracellular ion homeostasis so that the neuron can faithfully sustain spiking in response to the excitatory input. The second network includes two neurons coupled through mutual inhibitory synapses. Here we consider the role of astrocytic dendritic processes in maintaining anti-phase or synchronous oscillations. Dynamical systems methods, including bifurcation theory and fast/slow analysis, is used to systematically reduce the complex model to a simpler set of equations. In particular, the first network, consisting of differential equations for the neuron and astrocyte membrane potentials, channel state variables and intracellular and extracellular Na+ and K+ concentrations, is reduced to a one dimensional map. Fixed points of the map determine whether the astrocyte can maintain extracellular K+ homeostasis so the neuron can respond to periodic input. 

 

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omp2019.001.0063.pdf3.65 MB

Printed March 30, 2019;
Published ahead of print March 29, 2019; Printed March 30, 2019; OM&P 2019 Volume 5 Issue 1, pages 1-6; doi:10.20388/omp2019.001.0062
Abstract Full Text

Axo-axonal interactions of neuronal cells play an important role in functional development during embryogenesis. Axons of the cells formed on early stages of the brain development provide a template for the growing axons of later axons. However, the mechanisms of the guiding of younger axons by already formed axons are not well understood. In this study, we present a method to study such axo-axonal interactions in vitro using microfluidics methods and culturing neocortical cells. We studied the dynamics of axon growth in microchannels perpendicularly intersecting with other microchannels. This study provides fundamental understanding of the axonal navigation in microfluidic structures, which further facilitate the design of  experimental in vitro model for studying the role of already formed axons in the development of neuronal system.

 

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omp2019.001.0062_corrected.pdf21.78 MB

Published ahead of print December 20, 2018;
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In this study we examined the intersection of two molecular pathways both known to regulate dentate development – the Emx2 transcription factor and the Sonic Hedgehog (Shh) morphogenic scignaling pathway. We confirmed that Emx2 mutant mice have a markedly reduced dentate gyrus and studied evidence of changes in Shh signaling and Shh expression in these mutants. Our results indicate that loss of Emx2 affects the numbers and distribution of Gli+ ventrally derived dentate neural stem cells that are responsible for populating the perinatal dentate gyrus. Accompanying this, we find that Emx2 mutants have reduced expression of Shh in the amygdalo-hippocampal region. In addition, there are ectopic Shh responsive progenitors that fail to properly populate the dentate. Taken together our results indicate that Emx2 regulates dentate development in part by altering availability and signaling of Shh.

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omp2018.003.0060.pdf2.86 MB

Published ahead of print December 10, 2018;
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For many decades synaptic circuits have been associated solely with cell-cell neuronal connections represented by the presynaptic terminal, which releases a neurotransmitter, and the postsynaptic neuronal specialization, a site where the neurotransmitter can activate synaptic receptors. However, due to technical limitations these studies usually were linked only to the postsynaptic site. For a long while, the widespread techniques that rapidly advanced neurophysiology have been little used in understanding the way how Ca2+-dependent release of the excitatory neurotransmitter glutamate from neuronal axons can be measured directly. Only with the advance of live cell imaging, it became possible to detect internal Ca2+ dynamics in presynaptic boutons with the high temporal resolution.

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popov proof v2.pdf411.64 KB

Published ahead of print December 10, 2018;
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omp2018.003.0061.pdf2.06 MB

Published ahead of print September 18, 2018;
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Parkinson's disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used for in vitro disease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used for in vivo disease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomous in vivo disease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.

 

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omp2018.001.0057.pdf4.93 MB

Published ahead of print September 17, 2018;
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The convoluted human cerebral cortex is one of the key features that allows for an increased neuronal density packing essential for the complex cognitive and socioemotional behaviours man possesses. Nevertheless, the underlying mechanisms involved in cortical folding remained a both intriguing and functionally important enigma. A crucial component known to be involved in the formation and maintenance of all tissues is the extracellular matrix (ECM), providing scaffolds which tie tissues and organs in place. The composition of the ECM in both developing and mature structures is constantly remodelled, degraded and secreted by numerous types of cells, and its role as a source of growth factors and signalling in morphogenesis, migration, and proliferation is increasingly appreciated. Evidence for the differential expression of ECM during gyrification pinpoints its potentially fundamental role in shaping the folds of the cerebral cortex through both mechanical and molecular configurations. This review aims at addressing key ideas, potential directions and discoveries that highlight biomechanics of the ECM during the construction of the cortex cerebral gyrification. 

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omp2018.001.0058.pdf1.26 MB

Published ahead of print September 16, 2018;
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Vocalization is a highly conserved innate behavior in vertebrates. It is mainly used in social encounters to communicate a variety of information for inter- and intra- specific interactions. In this review, we focus on the anatomical, biomechanics and neuronal circuits underlying vocalization across vertebrate species. In addition, we discuss our recent findings that assign to the nucleus of the solitary tract a critical role in innate vocalization. This brain center receives viscerosensory information, i.e. information from internal organs that includes the lungs and the larynx. Furthermore, subpopulations of neurons in the nucleus of the solitary tract directly connect to and entrain the activity of expiratory and laryngeal motor neurons. In mammals and amphibians, these motor neurons control essential biomechanical parameters used for vocalization, and similar motor neuron pools regulate vocal utterances in birds. Thus vocalization relies on a conserved neuronal circuit residing in the brainstem and spinal cord. 

 

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omp2018.001.0059.pdf6.86 MB

Printed June 30, 2018;
Published ahead of print June 02, 2018; Printed June 30, 2018; OM&P 2018 Volume 4 Supplement S 1, pages 102-110; doi:10.20388/omp2018.00s1.006
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Cognitive neuroscience.pdf404.8 KB

Printed June 30, 2018;
Published ahead of print June 02, 2018; Printed June 30, 2018; OM&P 2018 Volume 4 Supplement S 1, pages 85-101; doi:10.20388/omp2018.00s1.005
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