Department of Molecular biophysics - Історія редагувань

Avi9526: Replaced content with "[https://new.biph.kiev.ua/en/home/structure/departments/department-of-molecular-biophysics/ Read more...]"

2020-10-25T23:07:45Z

Replaced content with "[https://new.biph.kiev.ua/en/home/structure/departments/department-of-molecular-biophysics/ Read more...]"

Показати зміни

Pasha: /* Members */

2020-03-01T21:58:41Z

Members

Pasha: /* References */

2020-02-25T17:42:49Z

References

Pasha: /* About */

2019-09-04T10:23:26Z

About

Amor: /* References */

2018-04-20T15:54:26Z

References

Amor: moved Laboratory of Molecular biophysics to Department of Molecular biophysics

2017-07-04T13:50:55Z

moved Laboratory of Molecular biophysics to Department of Molecular biophysics

Nana: /* About */

2016-02-27T10:32:39Z

About

Amor: /* Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents */

2015-11-25T18:20:01Z

Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents

Amor: /* Peripheral and central mechanisms underlying inflammatory chronic pain */

2015-11-25T18:19:05Z

Peripheral and central mechanisms underlying inflammatory chronic pain

Amor: /* Role of T-type Ca2+ channels in central processes of nociceptive neurons in maintenance of diabetic neuropathy */

2015-11-25T18:17:29Z

Role of T-type Ca2+ channels in central processes of nociceptive neurons in maintenance of diabetic neuropathy

@@ Рядок 110: / Рядок 110: @@
 |-style="background:#ccffcc;"
 |style="text-align:left;"|5.
-|Stepanyuk A.R.
+|Korogod S.M.
-|standrey@biph.kiev.ua
+|isabroad@gmail.com
-|380442562499
+|380442562053
 |-style="background:#ccffcc;"
 |style="text-align:left;"|6.
@@ Рядок 150: / Рядок 150: @@
 |-style="background:#ccffcc;"
 |style="text-align:left;"|13.
-|Edutenko M.
+|Kulagina I.
-|yedutenko@gmail.com
+|kulagina.iryna@gmail.com
-|380442562518
+|380442562053
 |-style="background:#ccffcc;"
-|style="text-align:left;"|14.
+|style="text-align:left;"|
-|Bozhenko A.
-|arsebo@biph.kiev.ua
-|380442562518
-|-style="background:#ccffcc;"
-|style="text-align:left;"|15.
-|Burdakova A.
-|nastia.burdakova@gmail.com
-|380442562428
-|-style="background:#ccffcc;"
-|style="text-align:left;"|16.
-|Osipenko D.
-|osipenkoden@gmail.com
-|380442562428
 |}

@@ Рядок 58: / Рядок 58: @@
 Continuing this research we have recently found that complete Freund adjuvant (CFA)-induced peripheral inflammation, a well-known model of chronic inflammatory pain, prominently augments excitatory neurotransmission in rat dorsal horn lamina II neurons exhibiting adapting firing patterns (Kopach et al., 2015) and apparently representing excitatory glutamatergic interneurons. At the same time this peripheral inflammation decreases excitatory drive to the tonic firing lamina II neurons most of which are inhibitory. The inhibitory drive is also increased to the inhibitory neurons and decreased to the excitatory ones as a result of the inflammation (Kopach et al., 2015). Thus, the balance between excitation and inhibition in the lamina II of dorsal horn is strongly shifted toward the excitation (Kopach et al., 2015). The lamina II interneurons directly synapse onto lamina I projection neurons (PNs), the main output of painful signaling in the spinal cord. Thus, these inflammatory-induced, neuron-type specific changes in synaptic activity in lamina II neurons most probably results in an increase of the excitatory drive and a decrease of the inhibitory drive to lamina I PNs. In its turn it may increase PN excitability, hence contributing to maintenance of the inflammatory pain. In this research we aim to test this hypothesis and to study what cellular and molecular mechanisms underlie increased excitability of PNs under inflammatory conditions.
-==='''References'''===
+==='''Recent References'''===
-#Kopach O, Viatchenko-Karpinski V, Atianjoh F, Belan P, Tao Y, and Voitenko N.  PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain.The Journal of Pain, 14(2):182-92. (2013). IF 4,5
+* Agashkov K, Krotov V, Krasniakova M, Shevchuk D, Andrianov Y, Zabenko Y. Distinct mechanisms of signal processing by lamina I spino- parabrachial neurons. Sci Rep. 9(1):19231 (2019). [https://www.ncbi.nlm.nih.gov/pubmed/?term=31848358 PMID:31848358]
-#Kopach O, Viatchenko-Karpinski V, Atianjoh F, Belan P, Tao Y, and Voitenko N. PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain. The Journal of Pain, 14(2):182-92. (2013). IF 4,5
+* Osypenko, D. S. et al. Perturbed Ca2+-dependent signaling of DYT2 hippocalcin mutant as mechanism of autosomal recessive dystonia. Neurobiol. Dis. 132, 104529 (2019). [https://www.ncbi.nlm.nih.gov/pubmed/?term=31301343 PMID:31301343]
-#Khomula, E.V., Viatchenko-Karpinski, V.Y., Borisyuk, A.L., Duzhyy D, Belan, P.V., Voitenko N.V. Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy  Biochimica et Biophysica Acta - Molecular Basis of Disease, 1832(5):636–649. (2013). IF 5,7
+* Krotov, V., Tokhtamysh, A., Safronov, B. V., Belan, P. & Voitenko, N. High-threshold primary afferent supply of spinal lamina X neurons. Pain 160, 1982–1988 (2019). [https://www.ncbi.nlm.nih.gov/pubmed/?term=30985620 PMID:30985620]
-#Stepanyuk AR, Borisyuk AL, Tsugorka TM, Belan PV Different pools of postsynaptic GABAA receptors mediate inhibition evoked by low‐and high‐frequency presynaptic stimulation at hippocampal synapses Synapse 68 (8), 344-354. (2014. IF 2,9)
+* Gryshchenko O, Gerasimenko J V, Peng S, Gerasimenko O V, Petersen OH. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology. J Physiol. 596(14):2663–78 (2018). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29424931 PMID:29424931]
-#Khomula, E.V., Borisyuk, A.L., Viatchenko-Karpinski, V.Y., Briede A, Belan, P.V., Voitenko N.V. Nociceptive neurons differentially express fast and slow T-type Ca 2+ currents in different types of diabetic neuropathy  Neural Plasticity. Epub (2014). IF 3,6
+* Bos R, Harris-Warrick RM, Brocard C, Demianenko LE, Manuel M, Zytnicki D, et al. Kv1.2 Channels Promote Nonlinear Spiking Motoneurons for Powering Up Locomotion. Cell Rep. 22(12):3315–27 (2018). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29562186 PMID:29562186]
-#Stepanyuk AR, Belan PV, Kononenko  A Model for the Fast Synchronous Oscillations of Firing Rate in Rat Suprachiasmatic Nucleus Neurons Cultured in a Multielectrode Array Dish. PloS one 9 (9), e106152. (2014). IF 4,4
+* Cherkas, V. et al. Measurement of intracellular concentration of fluorescently-labeled targets in living cells. PLoS One 13, e0194031 (2018). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29694385 PMID:29694385]
-#Stepanyuk A, Borisyuk A, Belan P  Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents. Frontiers in cellular neuroscience 8, 303. (2014). IF 4,6
+* Delmas P, Korogod S, Coste B. Biophysical mechanisms of pathological activity of neurons related to hypoxia-ischemic and inflammatory injuries. In: Noxious Mechanosensation The Oxford Handbook of the Neurobiology of Pain. (2018). DOI:10.13989/j.cnki.0517-6611.2015.11.042
-#Kopach, O., Krotov, V., Belan, P., Voitenko, N.  Inflammatory-induced changes in synaptic drive and postsynaptic AMPARs in lamina II dorsal horn neurons are cell-type specific. Pain, 156(3):428-38.(2015). IF 5,6
+* Savchenko A, Cherkas V, Liu C, Braun GB, Kleschevnikov A, Miller YI, et al. Graphene biointerfaces for optical stimulation of cells. Sci Adv. 4(5):eaat0351 (2018). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29795786 PMID:29795786]
-#Duzhyy, D.E., Viatchenko-Karpinski, V.Y., Khomula, E.V., Voitenko, N.V., Belan, P.V. Upregulation of T-type Ca<sup>2+</sup> channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. Molecular Pain. 20;11(1):29. (2015) IF 4,1
+* Peng S, Gerasimenko J V, Tsugorka TM, Gryshchenko O, Samarasinghe S, Petersen OH, et al. Galactose protects against cell damage in mouse models of acute pancreatitis. J Clin Invest. 128(9):3769–78 (2018). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29893744 PMID:29893744]
-#Kopach, O., Maistrenko, A., Lushnikova, I., Belan P, Skibo, G., Voitenko, N. HIF-1α-mediated upregulation of SERCA2b: The endogenous mechanism for alleviating the ischemia-induced intracellular Ca2+store dysfunction in CA1 and CA3 hippocampal neurons. Cell Calcium. 59(5):251-61. (2016). IF 4,3
+* Krotov, V. et al. Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation. Front. Cell. Neurosci. 11, 1–12 (2017). [https://www.ncbi.nlm.nih.gov/pubmed/?term=29163053 PMID:29163053]
-#Krotov V, Tokhtamysh A, Kopach O, Dromaretsky A, Sheremet Y, Belan P, Voitenko N. Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation. Frontiers in cellular neuroscience 11, 342. (2017). IF 4.6
+* Gryshchenko O, Gerasimenko J V, Gerasimenko O V, Petersen OH. Calcium signalling in pancreatic stellate cells: Mechanisms and potential roles. Cell Calcium 59(2–3):140–4 (2016). [https://www.ncbi.nlm.nih.gov/pubmed/?term=26960936 PMID:26960936]
 =='''Members'''==

@@ Рядок 1: / Рядок 1: @@
 =='''About'''==
-Laboratory of Molecular Biophysics has been established in April 2012 based on the research group headed by [[Pavel_Belan| Prof. P. Belan]] at the [[Department of General Physiology of Nervous System | Department of General Physiology of the Nervous System]]. Regulation of intracellular cytoplasmic Ca2+ concentration and Ca2+ signalling in different types of excitable cells as well as modulation of synaptic transmission in norm and pathology are the main subject of our research during recent years. Acutely isolated and primary cultured neurons as well as slices and ex vivo intact spinal cord preparation have been used in the experiments. Mainly, optical (digital imaging and confocal microscopy), conventional electrophysiological (microelectrodes, iontophoresis, patch clamp), genetic (transfection, infection, site-specific mutagenesis) and mathematical (simulation, statistics) methods and approaches have been employed in our studies.
+Department of Molecular Biophysics has been established in April 2017 based on the Laboratory of Molecular Biophysics headed by [[Pavel_Belan| Prof. P. Belan]] in the [[Department of General Physiology of Nervous System | Department of General Physiology of the Nervous System]]. Ca2+ signalling in different types of excitable cells as well as regulation of synaptic transmission in norm and pathology are the main subjects of our research during recent years. Acutely isolated and primary cultured neurons as well as slices and ex vivo intact spinal cord preparation have been used in the experiments. Mainly, optical (digital imaging and confocal microscopy), conventional electrophysiological (microelectrodes, iontophoresis, patch clamp), genetic (transfection, infection, site-specific mutagenesis) and mathematical (simulation, statistics) methods and approaches have been employed in our studies.
 =='''Research'''==

@@ Рядок 59: / Рядок 59: @@
 ==='''References'''===
-* Borisyuk A, Stepanyuk A, Belan P (2014) Activity-Dependent Potentiation of an Asynchronous Component of GABA-ergic Synaptic Currents in Cultured Hippocampal Neurons. [http://link.springer.com/article/10.1007/s11062-014-9400-2 Neurophysiology 46:10–15] [Accessed April 25, 2014].
+#Kopach O, Viatchenko-Karpinski V, Atianjoh F, Belan P, Tao Y, and Voitenko N.  PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain.The Journal of Pain, 14(2):182-92. (2013). IF 4,5
-* Dovgan a V, Cherkas VP, Stepanyuk a R, Fitzgerald DJ, Haynes LP, Tepikin a V, Burgoyne RD, Belan P V (2010) Decoding glutamate receptor activation by the Ca2+ sensor protein hippocalcin in rat hippocampal neurons. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3069492&tool=pmcentrez&rendertype=abstract Eur J Neurosci 32:347–358] [Accessed March 26, 2014].
+#Kopach O, Viatchenko-Karpinski V, Atianjoh F, Belan P, Tao Y, and Voitenko N. PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain. The Journal of Pain, 14(2):182-92. (2013). IF 4,5
-* Duzhyy DE, Viatchenko-Karpinski VY, Khomula E V, Voitenko N V, Belan P V (2015) Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4490764&tool=pmcentrez&rendertype=abstract Mol Pain 11:29] [Accessed August 11, 2015].
+#Khomula, E.V., Viatchenko-Karpinski, V.Y., Borisyuk, A.L., Duzhyy D, Belan, P.V., Voitenko N.V. Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy  Biochimica et Biophysica Acta - Molecular Basis of Disease, 1832(5):636–649. (2013). IF 5,7
-* Khomula E V, Borisyuk AL, Viatchenko-Karpinski VY, Briede A, Belan P V, Voitenko N V (2014) Nociceptive neurons differentially express fast and slow T-type ca(2+) currents in different types of diabetic neuropathy. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3945737&tool=pmcentrez&rendertype=abstract Neural Plast 2014:938235] [Accessed May 7, 2014].
+#Stepanyuk AR, Borisyuk AL, Tsugorka TM, Belan PV Different pools of postsynaptic GABAA receptors mediate inhibition evoked by low‐and high‐frequency presynaptic stimulation at hippocampal synapses Synapse 68 (8), 344-354. (2014. IF 2,9)
-* Khomula E V, Viatchenko-Karpinski VY, Borisyuk AL, Duzhyy DE, Belan P V, Voitenko N V (2013) Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy. [http://www.ncbi.nlm.nih.gov/pubmed/23376589 Biochim Biophys Acta 1832:636–649] [Accessed March 26, 2014].
+#Khomula, E.V., Borisyuk, A.L., Viatchenko-Karpinski, V.Y., Briede A, Belan, P.V., Voitenko N.V. Nociceptive neurons differentially express fast and slow T-type Ca 2+ currents in different types of diabetic neuropathy  Neural Plasticity. Epub (2014). IF 3,6
-* Kopach O, Krotov V, Belan P, Voitenko N (2015) Inflammatory-induced changes in synaptic drive and postsynaptic AMPARs in lamina II dorsal horn neurons are cell-type specific. [http://www.ncbi.nlm.nih.gov/pubmed/25599231 Pain 156:428–438] [Accessed February 22, 2015].
+#Stepanyuk AR, Belan PV, Kononenko  A Model for the Fast Synchronous Oscillations of Firing Rate in Rat Suprachiasmatic Nucleus Neurons Cultured in a Multielectrode Array Dish. PloS one 9 (9), e106152. (2014). IF 4,4
-* Kopach O, Voitenko N (2013) Extrasynaptic AMPA receptors in the dorsal horn: evidence and functional significance. [http://www.ncbi.nlm.nih.gov/pubmed/23194665 Brain Res Bull 93:47–56] [Accessed October 27, 2015].
+#Stepanyuk A, Borisyuk A, Belan P  Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents. Frontiers in cellular neuroscience 8, 303. (2014). IF 4,6
-* Stepanyuk A, Borisyuk A, Belan P (2014a) Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents. [http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00303/abstract Front Cell Neurosci 8:303] [Accessed October 6, 2014].
+#Kopach, O., Krotov, V., Belan, P., Voitenko, N.  Inflammatory-induced changes in synaptic drive and postsynaptic AMPARs in lamina II dorsal horn neurons are cell-type specific. Pain, 156(3):428-38.(2015). IF 5,6
-* Stepanyuk AR, Borisyuk AL, Belan P V (2011) Efficient maximum likelihood estimation of kinetic rate constants from macroscopic currents. Degtyar VE, ed. [http://dx.plos.org/10.1371/journal.pone.0029731 PLoS One 6:e29731] [Accessed May 8, 2014].
+#Duzhyy, D.E., Viatchenko-Karpinski, V.Y., Khomula, E.V., Voitenko, N.V., Belan, P.V. Upregulation of T-type Ca<sup>2+</sup> channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. Molecular Pain. 20;11(1):29. (2015) IF 4,1
-* Stepanyuk AR, Borisyuk AL, Tsugorka TM, Belan P V (2014b) Different pools of postsynaptic GABAA receptors mediate inhibition evoked by low- and high-frequency presynaptic stimulation at hippocampal synapses. [http://www.ncbi.nlm.nih.gov/pubmed/24677449 Synapse 68:344–354] [Accessed August 22, 2014].
+#Kopach, O., Maistrenko, A., Lushnikova, I., Belan P, Skibo, G., Voitenko, N. HIF-1α-mediated upregulation of SERCA2b: The endogenous mechanism for alleviating the ischemia-induced intracellular Ca2+store dysfunction in CA1 and CA3 hippocampal neurons. Cell Calcium. 59(5):251-61. (2016). IF 4,3
 =='''Members'''==

@@ Рядок 1: / Рядок 1: @@
 =='''About'''==
-Laboratory of Molecular Biophysics has been established in April 2012 based on the research group headed by [[Pavel_Belan| Dr. P. Belan]] at the [[Department of General Physiology of Nervous System | Department of General Physiology of the Nervous System]]. Regulation of intracellular cytoplasmic Ca2+ concentration and Ca2+ signalling in different types of excitable cells as well as modulation of synaptic transmission in norm and pathology are the main subject of our research during recent years. Acutely isolated and primary cultured neurons as well as slices and ex vivo intact spinal cord preparation have been used in the experiments. Mainly, optical (digital imaging and confocal microscopy), conventional electrophysiological (microelectrodes, iontophoresis, patch clamp), genetic (transfection, infection, site-specific mutagenesis) and mathematical (simulation, statistics) methods and approaches have been employed in our studies.
+Laboratory of Molecular Biophysics has been established in April 2012 based on the research group headed by [[Pavel_Belan| Prof. P. Belan]] at the [[Department of General Physiology of Nervous System | Department of General Physiology of the Nervous System]]. Regulation of intracellular cytoplasmic Ca2+ concentration and Ca2+ signalling in different types of excitable cells as well as modulation of synaptic transmission in norm and pathology are the main subject of our research during recent years. Acutely isolated and primary cultured neurons as well as slices and ex vivo intact spinal cord preparation have been used in the experiments. Mainly, optical (digital imaging and confocal microscopy), conventional electrophysiological (microelectrodes, iontophoresis, patch clamp), genetic (transfection, infection, site-specific mutagenesis) and mathematical (simulation, statistics) methods and approaches have been employed in our studies.
 =='''Research'''==

@@ Рядок 35: / Рядок 35: @@
 |-
 !width=400|[[File:LMB3.jpg]]
-!width=400|Figure 3. Schematic description of research.
+!width=400|Figure 3. ''Schematic description of research. Synaptic receptors embedded in the postsynaptic density (PSD) (A) are not accessible for single channel patch clamp recordings (C). At the same time macroscopic currents elicited in response to presynaptic stimulation of the channels are a sum of single-channel currents (C) and can be easily recorded in a whole-configuration. The new suggested methods use all information included in the statistical properties of macroscopic current fluctuations (C) and given appropriately recorded and filtered currents they can reliably estimate kinetic rates of realistically complex models (B) with accuracy of the single-channel analysis. They can also estimate unitary current (A) and the number of liganded and unliganded receptors in the PSD (A). The new methodology that will be developed in the framework of the project will also allow evaluating the size and topology of synaptic channel model (B) together with the biophysical parameters mentioned above''.
 Synaptic receptors embedded in the postsynaptic density (PSD) (A) are not accessible for single channel patch clamp recordings (C). At the same time macroscopic currents elicited in response to presynaptic stimulation of the channels are a sum of single-channel currents (C) and can be easily recorded in a whole-configuration. The new suggested methods use all information included in the statistical properties of macroscopic current fluctuations (C) and given appropriately recorded and filtered currents they can reliably estimate kinetic rates of realistically complex models (B) with accuracy of the single-channel analysis. They can also estimate unitary current (A) and the number of liganded and unliganded receptors in the PSD (A). The new methodology that will be developed in the framework of the project will also allow evaluating the size and topology of synaptic channel model (B) together with the biophysical parameters mentioned above.
 |}

@@ Рядок 54: / Рядок 54: @@
 |-
 !width=400|[[File:LMB4.jpg]]
-!width=400|Figure 4. AMPAR-mediated central sensitization in the DH. Tissue or nerve injury promotes an insertion of GluR1-containing, Ca2+-permeable AMPARs at the extrasynaptic sites followed by their increase in the synapses of the DH neurons with simultaneous internalization of GluR2-containing, Ca2+-impermeable AMPARs from the same synapses. Both of these processes lead to an increased Ca2+ influx into DH neurons, modulate neuronal signaling and finally result in spinal central sensitization and pain. Protein kinases (PKA and PKC) promote membrane insertion and internalization of AMPARs by phosphorylation of GluR1 and GluR2 receptor subunits.
+!width=400|Figure 4. ''AMPAR-mediated central sensitization in the DH. Tissue or nerve injury promotes an insertion of GluR1-containing, Ca2+-permeable AMPARs at the extrasynaptic sites followed by their increase in the synapses of the DH neurons with simultaneous internalization of GluR2-containing, Ca2+-impermeable AMPARs from the same synapses. Both of these processes lead to an increased Ca2+ influx into DH neurons, modulate neuronal signaling and finally result in spinal central sensitization and pain. Protein kinases (PKA and PKC) promote membrane insertion and internalization of AMPARs by phosphorylation of GluR1 and GluR2 receptor subunits''.
 |}
 Continuing this research we have recently found that complete Freund adjuvant (CFA)-induced peripheral inflammation, a well-known model of chronic inflammatory pain, prominently augments excitatory neurotransmission in rat dorsal horn lamina II neurons exhibiting adapting firing patterns (Kopach et al., 2015) and apparently representing excitatory glutamatergic interneurons. At the same time this peripheral inflammation decreases excitatory drive to the tonic firing lamina II neurons most of which are inhibitory. The inhibitory drive is also increased to the inhibitory neurons and decreased to the excitatory ones as a result of the inflammation (Kopach et al., 2015). Thus, the balance between excitation and inhibition in the lamina II of dorsal horn is strongly shifted toward the excitation (Kopach et al., 2015). The lamina II interneurons directly synapse onto lamina I projection neurons (PNs), the main output of painful signaling in the spinal cord. Thus, these inflammatory-induced, neuron-type specific changes in synaptic activity in lamina II neurons most probably results in an increase of the excitatory drive and a decrease of the inhibitory drive to lamina I PNs. In its turn it may increase PN excitability, hence contributing to maintenance of the inflammatory pain. In this research we aim to test this hypothesis and to study what cellular and molecular mechanisms underlie increased excitability of PNs under inflammatory conditions.
 ==='''References'''===

@@ Рядок 45: / Рядок 45: @@
 Role of T-type Ca2+ channels in central processes of nociceptive neurons in maintenance of diabetic neuropathy
-Peripheral diabetic neuropathy (PDN), occurring in about 60% - 70% of diabetic patients, is among the most severe consequences of diabetes. Chronic pain characterized by spontaneous deep aching or burning pain, as well as by mechanical allodynia and thermal hyperalgesia is one of the most disturbing symptoms of PDN. However, the specific cellular mechanisms responsible for development and maintenance of peripheral diabetic neuropathy are mainly unknown. We have recently found that different types of nociceptive DRG neurons demonstrate diabetes-induced upregulation of CaV3.2 subtype of T-type Ca2+ channels during different stages of diabetes development (Khomula et al., 2013)(Khomula et al., 2014)(Duzhyy et al., 2015). The upregulation of T-type channels resulted in the increased neuronal excitability of nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. The upregulation T-type channels and increased excitability of neurons may contribute to thermal hyperalgesia in early diabetes and nonthermal nociception (e.g. mechanical allodynia and hyperalgesia and spontaneous pain) at its later-stage. We hypothesize that T-type Ca2+ channels are functionally expressed in central nociceptive processes and that upregulation of these channels under diabetic conditions amplifies peripheral action potentials in these neurons to busting discharges leading to changes in nociceptive output of lamina I projection neurons of the spinal cord and maintenance of painful diabetic neuropathy. Since direct electrophysiological measurements of T-type channel functioning in central axons of nociceptive DRG neurons are not methodologically feasible we are testing this hypothesis by an innovative combination of state-of-the-art approaches that include a novel whole spinal cord preparation that preserves the complex organization of dorsal roots in the spinal cord, Ca2+ imaging in identified central axons of specific types of primary nociceptive neurons using genetic Ca2+ indicators and profound computer modelling.
+Peripheral diabetic neuropathy (PDN), occurring in about 60% - 70% of diabetic patients, is among the most severe consequences of diabetes. Chronic pain characterized by spontaneous deep aching or burning pain, as well as by mechanical allodynia and thermal hyperalgesia is one of the most disturbing symptoms of PDN. However, the specific cellular mechanisms responsible for development and maintenance of peripheral diabetic neuropathy are mainly unknown. We have recently found that different types of nociceptive DRG neurons demonstrate diabetes-induced upregulation of CaV3.2 subtype of T-type Ca2+ channels during different stages of diabetes development (Khomula et al., 2013)(Khomula et al., 2014)(Duzhyy et al., 2015). The upregulation of T-type channels resulted in the increased neuronal excitability of nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. The upregulation T-type channels and increased excitability of neurons may contribute to thermal hyperalgesia in early diabetes and nonthermal nociception (e.g. mechanical allodynia and hyperalgesia and spontaneous pain) at its later-stage. We hypothesize that '''''T-type Ca2+ channels are functionally expressed in central nociceptive processes and that upregulation of these channels under diabetic conditions amplifies peripheral action potentials in these neurons to busting discharges leading to changes in nociceptive output of lamina I projection neurons of the spinal cord and maintenance of painful diabetic neuropathy'''''. Since direct electrophysiological measurements of T-type channel functioning in central axons of nociceptive DRG neurons are not methodologically feasible we are testing this hypothesis by an innovative combination of state-of-the-art approaches that include a novel whole spinal cord preparation that preserves the complex organization of dorsal roots in the spinal cord, Ca2+ imaging in identified central axons of specific types of primary nociceptive neurons using genetic Ca2+ indicators and profound computer modelling.
 ===='''Peripheral and central mechanisms underlying inflammatory chronic pain'''====