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Papers by Isabella Silkis
The Journal of Physiology, 1979
1. Prolonged changes in the excitability of cortical neurones can be produced by altering their f... more 1. Prolonged changes in the excitability of cortical neurones can be produced by altering their firing rates for brief periods. In the anaesthetized cat, increased firing of pyramidal tract cells induced by trains of antidromic conditioning shocks led to increases in cell excitability, as measured by the size of the mass response at the medullary pyramid to test shocks applied to the cortical surface. We have shown in two ways that post‐synaptic mechanisms could be responsible. 2. In one experimental design, MgCl2 solution (1 mole/l.) was applied to the cortical surface in order to block synaptic activity throughout the cortical depth. Following antidromic conditioning trains, cell excitability was increased; the size of the mass response was up to 30% larger than the control values. This persisted undiminished for up to 3 hr. 3. In the second experimental design, synaptic activity was not blocked, but we compared the effects of antidromic plus synaptic activation of pyramidal tract...
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
ABSTRACT
Uspekhi fiziologicheskikh nauk
A possible mechanism of involvement of the subthalamic nucleus (STN) in movement disorders evoked... more A possible mechanism of involvement of the subthalamic nucleus (STN) in movement disorders evoked by dopamine deficit is suggested. Multifunctional role of the STN is based on following reasons. Various STN cells participate in the cortico-basal ganglia-thalamocortical loop and in the basal ganglia-pedunculopontine-basal ganglia loop. Complexity of neural circuits is determined by functional heterogeneity of neurons in the nuclei, reciprocally connected with the STN, as well as by opposite modulation of activity of these neurons by dopamine due to activation of different types of pre- and postsynaptic receptors. Dopamine influences activity of STN neurons directly, through pre- and postsynaptic receptors. It is assumed that high-frequency stimulation of the STN can reduce or eliminate Parkinsonian symptoms not only owing to inhibition of activity of GABAergic neurons in the output basal ganglia nuclei, projected into the thalamus or pedunculopontine nucleus, but also due to excitati...
Neir̆ofiziologiia = Neurophysiology, 1979
Interaction between 3-4 neighbouring neurons in the visual cortex of awakening cats was examined ... more Interaction between 3-4 neighbouring neurons in the visual cortex of awakening cats was examined using a cross-correlation analysis. In some microsystems neurons revealed a tendency towards synchronized activity indicating a shared excitatory input. In other microsystems asymmetrical interaction was observed: neurons with larger spike amplitudes exhibited excitatory effect on neurons with smaller spike amplitudes (latent period about 5 ms) and neurons with small spike amplitudes inhibited neurons with large spike amplitudes (latent period 1-8 ms, duration of inhibition 30-200 ms). Suggestions were made about the existence of recurrent inhibition and inhibitory interneurons in microsystems of the visual cortex.
Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova
It is shown that in the neocortex (like in the hippocampus) the long-term heterosynaptic depressi... more It is shown that in the neocortex (like in the hippocampus) the long-term heterosynaptic depression (LTD) may exist. The effect appears as a long-term decrease of the probability of the monosynaptic responses in the afferent input to the recorded neuron after the conditioning tetanization of the other afferent input to the same neuron. The main properties of the heterosynaptic LTD are its longevity, cooperativity and lack of input specificity. The heterosynaptic LTD in the unconditioned input and the LTP or the homosynaptic LTD in the conditioned input can develop in parallel or independently of each other. It is supposed that the heterosynaptic LTD (like the LTP and the homosynaptic LTD) is Ca-dependent phenomenon and for its induction a certain level of depolarization of the membrane under the inactive (during conditioning) synapses must be achieved. The heterosynaptic LTD may provide for the "contrasting", i.e. the relative increase of the efficiency of the activated sy...
Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova
Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes... more Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes of action potentials to photic, acoustic and electro-cutaneous stimuli were studied. It was shown that N1 neurones as differing from N3 were predominantly polymodal, often reacted with inhibitory responses and their background activity was characterized by random distribution of interstimuli intervals. Inputs for heteromodal stimuli were found to differ in N1 and N3 neurones. The results suggest existence of functional heterogeneity of neurones, recorded with different action potential amplitudes.
Neuroscience and Behavioral Physiology, 1985
ABSTRACT
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk, 2001
On the basis of earlier suggested unitary mechanism of synaptic plasticity opposite effects of ad... more On the basis of earlier suggested unitary mechanism of synaptic plasticity opposite effects of adenosine and dopamine on the cAMP concentration in striatal spinal cells can emphasize the well known antagonistic interactions between A2A and D2 receptors on striatopallidal cells and between A1 and D1 receptors on striatonigral cells. This is due to that both the dopamine agonist and adenosine antagonist must promote the induction of long-term potentiation/depression of efficacy of excitatory cortical inputs to striatopallidal/striatonigral cells. This modification must lead to synergistic disinhibition of thalamic cells via "direct" and "indirect" pathways through basal ganglia and subsequent strengthening of motor activity.
Neurochemical Journal, 2014
Abbreviations: BG, basal ganglia; PD, Parkinson's disease; GPe and GPi, external and internal par... more Abbreviations: BG, basal ganglia; PD, Parkinson's disease; GPe and GPi, external and internal parts of the globus pallidus; VTA, ventral tegmental area; GSIs, GABAergic striatal inter neurons; LTD, long term depression; LTP, long term potentia tion; C-BG-Th-C, neural network cortex-basal gangliathalamus-cortex; NA, nucleus accumbens; TANs, tonically active striatal neurons; CSNs, cholinergic striatal neurons; CN, caudate nucleus; SNc and SNr, substantia nigra pars com pacta and substantia nigra pars reticulate; SSNs, spiny striatal neurons.
Neurochemical Journal, 2007
A possible mechanism underlying the role of opioids in the treatment of Parkinson's disease and L... more A possible mechanism underlying the role of opioids in the treatment of Parkinson's disease and L-dopa-induced dyskinesias is suggested. This role is based on the reorganization of neuronal firing in the motor cortico-basal ganglia-thalamocortical loop as a consequence of opioid-mediated LTD induction in the spiny cells of the input basal ganglia nucleus, striatum. Analysis of existing data allowed us to propose that the striatonigral cells in the striosomes and matrix that release dynorphin mainly express µ and κ opioid receptors, respectively, whereas striatopallidal cells that release enkephalin express δ opioid receptors. The proposed mechanism implies that in addition to agonists of dopamine receptors and antagonists of muscarinic receptors, µ and δ receptor agonists and/or κ receptor antagonists might alleviate the symptoms of Parkinson's disease and allow recovery of locomotor activity. Recurrent collaterals of striatal spiny cells innervating their dendrites and bodies, as well as those of striatal cholinergic interneurons, form negative feedback loops that allow opioid peptides and substance P to regulate and stabilize striatal output pathways. Therefore, in the absence of activation of the D2 and D1 receptors on striatal spiny cells, increased enkephalin concentration and decreased dynorphin and substance P level promote the suppression of acetylcholine release (due to modulation of cholinergic interneuron firing through δ opioid and NK receptors), thus reducing the impact of a dopamine deficit on basal ganglia functioning. Opposing changes in opioid concentrations, due to L-dopa treatment and reorganization of activity in the same neuronal loops, may reduce dyskinesias.
The Second International Symposium on Neuroinformatics and Neurocomputers
The existence of Hebbian-like learning rules was supported by numerous experiments on excitatoty ... more The existence of Hebbian-like learning rules was supported by numerous experiments on excitatoty glutamatergic synapses. Two forms of long-term modification of excitatory synaptic transmissionpotentiation (LTPe) and depression (LTDe) were demonstrated. Both effects are input specific, depend on cotrelation between presynaptic activity and postsywptic response, and require increase in postsynaptic Gaff ion concentration (Ca",) [1,2,3], There are experimental evidences that the large surge in CaHP (designed Ca*l) triggers LTPe by activation of ea*-dependent protein kinases (PKs), phosphorylation of ionotropic AMPA and NMDA receptors (AMPARs, NMDARs), and increasing of their sensitivity (Fig.1). The moderate elevation of Ca'+p (designed Ca",) leads to LTDe by Ca*depended (by the use of calcinenrrin) activation of protein phosphatases (PPs), dephosphorylation of AMPARs and NMDARs, and decreasing of their sensitivity (Fig.1). [l]. Thus the balance between PKs and PPs determine the type of excitatory transmission modification.
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
ABSTRACT
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk, 2004
A possible mechanism of influence of neuromodulators on interdependent activity of neurons in the... more A possible mechanism of influence of neuromodulators on interdependent activity of neurons in the diverse basal ganglia nuclei is suggested. According to modulation rules, an activation of postsynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes induction of long-term potentiation (depression) of excitatory inputs to different neurons and augmentation (lowering) of their activity; an activation of presynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes a rise (decrease) of release of GABA and co-peptides from striatal terminals and glutamate release from subthalamic terminals in the globus pallidus and output nuclei. It follows from the modulation rules that, since identical receptors are present on striatal neuron and their axon terminals, effects of neuromodulator action in diverse basal ganglia nuclei can be summarized. Neuromodulators released from striato-nigral and striato-pallidal fibers could promote interdependent activity of neurons in "direct&...
The Journal of Physiology, 1979
1. Prolonged changes in the excitability of cortical neurones can be produced by altering their f... more 1. Prolonged changes in the excitability of cortical neurones can be produced by altering their firing rates for brief periods. In the anaesthetized cat, increased firing of pyramidal tract cells induced by trains of antidromic conditioning shocks led to increases in cell excitability, as measured by the size of the mass response at the medullary pyramid to test shocks applied to the cortical surface. We have shown in two ways that post‐synaptic mechanisms could be responsible. 2. In one experimental design, MgCl2 solution (1 mole/l.) was applied to the cortical surface in order to block synaptic activity throughout the cortical depth. Following antidromic conditioning trains, cell excitability was increased; the size of the mass response was up to 30% larger than the control values. This persisted undiminished for up to 3 hr. 3. In the second experimental design, synaptic activity was not blocked, but we compared the effects of antidromic plus synaptic activation of pyramidal tract...
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
ABSTRACT
Uspekhi fiziologicheskikh nauk
A possible mechanism of involvement of the subthalamic nucleus (STN) in movement disorders evoked... more A possible mechanism of involvement of the subthalamic nucleus (STN) in movement disorders evoked by dopamine deficit is suggested. Multifunctional role of the STN is based on following reasons. Various STN cells participate in the cortico-basal ganglia-thalamocortical loop and in the basal ganglia-pedunculopontine-basal ganglia loop. Complexity of neural circuits is determined by functional heterogeneity of neurons in the nuclei, reciprocally connected with the STN, as well as by opposite modulation of activity of these neurons by dopamine due to activation of different types of pre- and postsynaptic receptors. Dopamine influences activity of STN neurons directly, through pre- and postsynaptic receptors. It is assumed that high-frequency stimulation of the STN can reduce or eliminate Parkinsonian symptoms not only owing to inhibition of activity of GABAergic neurons in the output basal ganglia nuclei, projected into the thalamus or pedunculopontine nucleus, but also due to excitati...
Neir̆ofiziologiia = Neurophysiology, 1979
Interaction between 3-4 neighbouring neurons in the visual cortex of awakening cats was examined ... more Interaction between 3-4 neighbouring neurons in the visual cortex of awakening cats was examined using a cross-correlation analysis. In some microsystems neurons revealed a tendency towards synchronized activity indicating a shared excitatory input. In other microsystems asymmetrical interaction was observed: neurons with larger spike amplitudes exhibited excitatory effect on neurons with smaller spike amplitudes (latent period about 5 ms) and neurons with small spike amplitudes inhibited neurons with large spike amplitudes (latent period 1-8 ms, duration of inhibition 30-200 ms). Suggestions were made about the existence of recurrent inhibition and inhibitory interneurons in microsystems of the visual cortex.
Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova
It is shown that in the neocortex (like in the hippocampus) the long-term heterosynaptic depressi... more It is shown that in the neocortex (like in the hippocampus) the long-term heterosynaptic depression (LTD) may exist. The effect appears as a long-term decrease of the probability of the monosynaptic responses in the afferent input to the recorded neuron after the conditioning tetanization of the other afferent input to the same neuron. The main properties of the heterosynaptic LTD are its longevity, cooperativity and lack of input specificity. The heterosynaptic LTD in the unconditioned input and the LTP or the homosynaptic LTD in the conditioned input can develop in parallel or independently of each other. It is supposed that the heterosynaptic LTD (like the LTP and the homosynaptic LTD) is Ca-dependent phenomenon and for its induction a certain level of depolarization of the membrane under the inactive (during conditioning) synapses must be achieved. The heterosynaptic LTD may provide for the "contrasting", i.e. the relative increase of the efficiency of the activated sy...
Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova
Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes... more Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes of action potentials to photic, acoustic and electro-cutaneous stimuli were studied. It was shown that N1 neurones as differing from N3 were predominantly polymodal, often reacted with inhibitory responses and their background activity was characterized by random distribution of interstimuli intervals. Inputs for heteromodal stimuli were found to differ in N1 and N3 neurones. The results suggest existence of functional heterogeneity of neurones, recorded with different action potential amplitudes.
Neuroscience and Behavioral Physiology, 1985
ABSTRACT
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk, 2001
On the basis of earlier suggested unitary mechanism of synaptic plasticity opposite effects of ad... more On the basis of earlier suggested unitary mechanism of synaptic plasticity opposite effects of adenosine and dopamine on the cAMP concentration in striatal spinal cells can emphasize the well known antagonistic interactions between A2A and D2 receptors on striatopallidal cells and between A1 and D1 receptors on striatonigral cells. This is due to that both the dopamine agonist and adenosine antagonist must promote the induction of long-term potentiation/depression of efficacy of excitatory cortical inputs to striatopallidal/striatonigral cells. This modification must lead to synergistic disinhibition of thalamic cells via "direct" and "indirect" pathways through basal ganglia and subsequent strengthening of motor activity.
Neurochemical Journal, 2014
Abbreviations: BG, basal ganglia; PD, Parkinson's disease; GPe and GPi, external and internal par... more Abbreviations: BG, basal ganglia; PD, Parkinson's disease; GPe and GPi, external and internal parts of the globus pallidus; VTA, ventral tegmental area; GSIs, GABAergic striatal inter neurons; LTD, long term depression; LTP, long term potentia tion; C-BG-Th-C, neural network cortex-basal gangliathalamus-cortex; NA, nucleus accumbens; TANs, tonically active striatal neurons; CSNs, cholinergic striatal neurons; CN, caudate nucleus; SNc and SNr, substantia nigra pars com pacta and substantia nigra pars reticulate; SSNs, spiny striatal neurons.
Neurochemical Journal, 2007
A possible mechanism underlying the role of opioids in the treatment of Parkinson's disease and L... more A possible mechanism underlying the role of opioids in the treatment of Parkinson's disease and L-dopa-induced dyskinesias is suggested. This role is based on the reorganization of neuronal firing in the motor cortico-basal ganglia-thalamocortical loop as a consequence of opioid-mediated LTD induction in the spiny cells of the input basal ganglia nucleus, striatum. Analysis of existing data allowed us to propose that the striatonigral cells in the striosomes and matrix that release dynorphin mainly express µ and κ opioid receptors, respectively, whereas striatopallidal cells that release enkephalin express δ opioid receptors. The proposed mechanism implies that in addition to agonists of dopamine receptors and antagonists of muscarinic receptors, µ and δ receptor agonists and/or κ receptor antagonists might alleviate the symptoms of Parkinson's disease and allow recovery of locomotor activity. Recurrent collaterals of striatal spiny cells innervating their dendrites and bodies, as well as those of striatal cholinergic interneurons, form negative feedback loops that allow opioid peptides and substance P to regulate and stabilize striatal output pathways. Therefore, in the absence of activation of the D2 and D1 receptors on striatal spiny cells, increased enkephalin concentration and decreased dynorphin and substance P level promote the suppression of acetylcholine release (due to modulation of cholinergic interneuron firing through δ opioid and NK receptors), thus reducing the impact of a dopamine deficit on basal ganglia functioning. Opposing changes in opioid concentrations, due to L-dopa treatment and reorganization of activity in the same neuronal loops, may reduce dyskinesias.
The Second International Symposium on Neuroinformatics and Neurocomputers
The existence of Hebbian-like learning rules was supported by numerous experiments on excitatoty ... more The existence of Hebbian-like learning rules was supported by numerous experiments on excitatoty glutamatergic synapses. Two forms of long-term modification of excitatory synaptic transmissionpotentiation (LTPe) and depression (LTDe) were demonstrated. Both effects are input specific, depend on cotrelation between presynaptic activity and postsywptic response, and require increase in postsynaptic Gaff ion concentration (Ca",) [1,2,3], There are experimental evidences that the large surge in CaHP (designed Ca*l) triggers LTPe by activation of ea*-dependent protein kinases (PKs), phosphorylation of ionotropic AMPA and NMDA receptors (AMPARs, NMDARs), and increasing of their sensitivity (Fig.1). The moderate elevation of Ca'+p (designed Ca",) leads to LTDe by Ca*depended (by the use of calcinenrrin) activation of protein phosphatases (PPs), dephosphorylation of AMPARs and NMDARs, and decreasing of their sensitivity (Fig.1). [l]. Thus the balance between PKs and PPs determine the type of excitatory transmission modification.
Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova
ABSTRACT
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk, 2004
A possible mechanism of influence of neuromodulators on interdependent activity of neurons in the... more A possible mechanism of influence of neuromodulators on interdependent activity of neurons in the diverse basal ganglia nuclei is suggested. According to modulation rules, an activation of postsynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes induction of long-term potentiation (depression) of excitatory inputs to different neurons and augmentation (lowering) of their activity; an activation of presynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes a rise (decrease) of release of GABA and co-peptides from striatal terminals and glutamate release from subthalamic terminals in the globus pallidus and output nuclei. It follows from the modulation rules that, since identical receptors are present on striatal neuron and their axon terminals, effects of neuromodulator action in diverse basal ganglia nuclei can be summarized. Neuromodulators released from striato-nigral and striato-pallidal fibers could promote interdependent activity of neurons in "direct&...