- Email: [email protected]
S7.3 Differential connectivity changes in the oscillatory activity of the cortex and basal ganglia from a model of Parkinsonian rats: effect of dopamine agonist
14th ECCN / 4th ICTMS/DCS
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research. 1985 Oct; 345(1): 68 78. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/2998549 Monosov IE, Trageser JC, Thompson KG. Measurements of simultaneously recorded spiking activity and local field potentials suggest that spatial selection emerges in the frontal eye field. [Internet]. Neuron. 2008 Feb; 57(4): 614 25. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/18304489 Murthy VN, Fetz EE. Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. [Internet]. Proceedings of the National Academy of Sciences of the United States of America. 1992 Jun; 89(12): 5670 4. Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid= 49354&tool=pmcentrez&rendertype=abstract Qi H-X, Jain N, Collins CE, Lyon DC, Kaas JH. Functional organization of motor cortex of adult macaque monkeys is altered by sensory loss in infancy. [Internet]. Proceedings of the National Academy of Sciences of the United States of America. 2010 Feb; 107(7): 3192 7. Available from: http:// www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2840311& tool=pmcentrez&rendertype=abstract Sessle B, Wiesendanger M. Structural and functional definition of the motor cortex in the monkey (Macaca fascicularis) [Internet]. The Journal of Physiology. 1982; 323(1): 245. Available from: http:// jp.physoc.org/content/323/1/245.short Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. [Internet]. Brain: a journal of neurology. 2000 Mar; 123 Pt 3572 84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 10686179 Witham C, Wang M, Baker S. Cells in somatosensory areas show synchrony with beta oscillations in monkey motor cortex [Internet]. European Journal of. 2007; 26. Available from: http:// www3.interscience.wiley.com/journal/118543043/abstract Witham CL, Wang M, Baker SN. Corticomuscular coherence between motor cortex, somatosensory areas and forearm muscles in the monkey. [Internet]. Frontiers in systems neuroscience. 2010 Jan; 4(July): 1 14. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/20740079 Womelsdorf T, Schoffelen J-M, Oostenveld R, Singer W, Desimone R, Engel AK, et al. Modulation of neuronal interactions through neuronal synchronization. [Internet]. Science (New York, N.Y.). 2007 Jun; 316(5831): 1609 12. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/17569862
S7.3 Differential connectivity changes in the oscillatory activity of the cortex and basal ganglia from a model of Parkinsonian rats: effect of dopamine agonist as1 , J. L´ opez-Azc´ arate1 , M. Alegre2 , F. de Vico M. Valencia1 , M.J. Nicol´ Fallani3 , L. Astolfi4 , J. Toppi4 , F. Babiloni3 , J. Artieda2 1 Division of Neurosciences, CIMA, University of Navarra, Pamplona, Spain, 2 Division of Neurosciences, CIMA and Clinical Neurophysiology Section, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain, 3 Neuroelectrical Imaging and BCI lab, IRCCS Fondazione Santa Lucia and Department of Physiology and Pharmacology, University of Rome “Sapienza”, Rome, Italy, 4 Neuroelectrical Imaging and BCI lab, IRCCS Fondazione Santa Lucia and Department of Computer and Systems Science, University of Rome “Sapienza”, Rome, Italy 6-hydroxydopamine (6-OHDA) lesioned rats show abnormal beta activity (20 Hz) in cortex and subthalamic nucleus, which is reduced after apomorphine administration. These changes are similar to those observed in patients with Parkinson’s disease recorded in the STN in the “off” and “on” medication states. After L-DOPA or dopaminergic agonist intake (“ON” state) PD patients show an increase in gamma activity in the STN that has also been observed in lesioned rats. The aim of our study was to check how apomorphine modulates the interactions in the motor circuit of the basal ganglia in control and 6-OHDA rats. We recorded local field potentials (LFP) in 6 control and 6 6-OHDA lesioned Wistar male rats in motor cortex (Cx), caudate-putamen (CPU), subthalamic area (STN) and substantia nigra pars reticulata (SNr), before and after the administration of apomorphine (5 mg/Kg ip). The recording sessions lasted at least
S19 80 minutes, 20 before and 60 after apomorphine administation. Signals from artifact-free recordings were analyzed by means of Partial Directed in the frequency Coherence, a technique that allows estimating domain how the information propagates among the structures. In basal condition, 6-OHDA rats showed interactions in the beta band between Cx and basal ganglia whereas no interactions were found for the control animals. Apomorphine administration induced interactions in the low gamma band (40 Hz) in both; control and lesioned rats (mainly between CPU/STN and Cx) while control animals presented a higher degree of interaction. In the high gamma range (80 Hz), lesioned rats presented interactions between CPU STN, STN Cx and CPU Cx, while control rats lost the CPU Cx interaction. 6-OHDA lesion modifies how structures in the motor circuit of the basal ganglia interact in the beta band and determines how interactions are modulated by apomorfine administration. This work has been partially supported by the grant FIS 070034 and by the UTE Proyecto CIMA. S7.4 Effects of different forms of amyloid b-peptide on synaptic function C. Ripoli1 , E. Riccardi1 , R. Piacentini1 , G. Bitan2 , C. Grassi1 Institute of Human Physiology, Catholic University Medical School, Rome, Italy, 2 Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States 1
Introduction: In early stages of Alzheimer’s disease, that precede plaque formation and neuronal death, cognitive deficits are likely the result of synaptic function impairment. The key initiating pathogenic event is the accumulation of neurotoxic aggregates of amyloid b-peptide (Ab) in hippocampus and cortex. We previously demonstrated that the redox state of methionine in position 35 (Met35) plays a critical role in Ab toxicity. Objective: To determine whether oxidation of Met35 also influences Ab synaptotoxicity we investigated the effects of 20-min lasting perfusion with 200 nM AbWT and its oxidized analogues (AbMet35(O) , AbMet35(O2) ) on synaptic transmission and plasticity, and on synaptophysin (Syn) expression. Methods: We performed electrophysiological experiment on hippocampal brain slices and autaptic neurons to study the long-term potentiation (LTP) and synaptic transmission. We also studied Syn density as the ratio between Syn fluorescence intensity and MAP2 labeled area by confocal microscopy. Results: In control slices, 60 min after tetanus fEPSP amplitude (A) and slope (S) were increased by 138% and 132% of baseline, respectively. This potentiation was significantly lower after AbWT treatment (A: +72%; S: +68%; P < 0.001) whereas no changes in LTP were observed in slices exposed to AbMet35(O) . Surprisingly, AbMet35(O2) reduced the synaptic plasticity to the same level as AbWT . In autaptic microcultures, AbWT and AbMet35(O2) significantly reduced the amplitude of EPSCs evoked by action potentials and mEPSC frequency (P < 0.05) whereas AbMet35(O) had no effects on basal synaptic transmission. Finally, AbWT and AbMet35(O2) significantly reduced Syn density while AbMet35(O) did not affect presynaptic terminals. Conclusion: Our results indicate that the chemical state of Met35 plays a key role in Ab- induced: (i) synaptic depression, (ii) inhibition of synaptic plasticity and (iii) alterations in the expression of proteins relevant for the synaptic function. S7.5 Effects of membrane polarisation on velocity recovery cycles of human muscle fibres in-vivo R. Arunachalam1 , D. Allen1 , C.E.G. Moore2 1 Department of Clinical Neurophysiology, Wessex Neurological Centre, Southampton, United Kingdom, 2 Department of Clinical Neurophysiology, Queen Alexandra Hospital, Portsmouth, United Kingdom Introduction: Techniques capable of measuring components of muscle fibre membrane excitability, akin to nerve excitability testing, show promise in understanding muscle pathophysiology. Automated measurement of velocity recovery cycles (VRC) after direct muscle fibre stimulation has recently been developed. The early supernormality (SN10) reflects membrane capacitance; the late supernormality (SN100) reflects T-tubule function [1,2].
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[10]
[11]
[12]
[13]
[14]
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research. 1985 Oct; 345(1): 68 78. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/2998549 Monosov IE, Trageser JC, Thompson KG. Measurements of simultaneously recorded spiking activity and local field potentials suggest that spatial selection emerges in the frontal eye field. [Internet]. Neuron. 2008 Feb; 57(4): 614 25. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/18304489 Murthy VN, Fetz EE. Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. [Internet]. Proceedings of the National Academy of Sciences of the United States of America. 1992 Jun; 89(12): 5670 4. Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid= 49354&tool=pmcentrez&rendertype=abstract Qi H-X, Jain N, Collins CE, Lyon DC, Kaas JH. Functional organization of motor cortex of adult macaque monkeys is altered by sensory loss in infancy. [Internet]. Proceedings of the National Academy of Sciences of the United States of America. 2010 Feb; 107(7): 3192 7. Available from: http:// www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2840311& tool=pmcentrez&rendertype=abstract Sessle B, Wiesendanger M. Structural and functional definition of the motor cortex in the monkey (Macaca fascicularis) [Internet]. The Journal of Physiology. 1982; 323(1): 245. Available from: http:// jp.physoc.org/content/323/1/245.short Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. [Internet]. Brain: a journal of neurology. 2000 Mar; 123 Pt 3572 84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 10686179 Witham C, Wang M, Baker S. Cells in somatosensory areas show synchrony with beta oscillations in monkey motor cortex [Internet]. European Journal of. 2007; 26. Available from: http:// www3.interscience.wiley.com/journal/118543043/abstract Witham CL, Wang M, Baker SN. Corticomuscular coherence between motor cortex, somatosensory areas and forearm muscles in the monkey. [Internet]. Frontiers in systems neuroscience. 2010 Jan; 4(July): 1 14. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/20740079 Womelsdorf T, Schoffelen J-M, Oostenveld R, Singer W, Desimone R, Engel AK, et al. Modulation of neuronal interactions through neuronal synchronization. [Internet]. Science (New York, N.Y.). 2007 Jun; 316(5831): 1609 12. Available from: http:// www.ncbi.nlm.nih.gov/pubmed/17569862
S7.3 Differential connectivity changes in the oscillatory activity of the cortex and basal ganglia from a model of Parkinsonian rats: effect of dopamine agonist as1 , J. L´ opez-Azc´ arate1 , M. Alegre2 , F. de Vico M. Valencia1 , M.J. Nicol´ Fallani3 , L. Astolfi4 , J. Toppi4 , F. Babiloni3 , J. Artieda2 1 Division of Neurosciences, CIMA, University of Navarra, Pamplona, Spain, 2 Division of Neurosciences, CIMA and Clinical Neurophysiology Section, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain, 3 Neuroelectrical Imaging and BCI lab, IRCCS Fondazione Santa Lucia and Department of Physiology and Pharmacology, University of Rome “Sapienza”, Rome, Italy, 4 Neuroelectrical Imaging and BCI lab, IRCCS Fondazione Santa Lucia and Department of Computer and Systems Science, University of Rome “Sapienza”, Rome, Italy 6-hydroxydopamine (6-OHDA) lesioned rats show abnormal beta activity (20 Hz) in cortex and subthalamic nucleus, which is reduced after apomorphine administration. These changes are similar to those observed in patients with Parkinson’s disease recorded in the STN in the “off” and “on” medication states. After L-DOPA or dopaminergic agonist intake (“ON” state) PD patients show an increase in gamma activity in the STN that has also been observed in lesioned rats. The aim of our study was to check how apomorphine modulates the interactions in the motor circuit of the basal ganglia in control and 6-OHDA rats. We recorded local field potentials (LFP) in 6 control and 6 6-OHDA lesioned Wistar male rats in motor cortex (Cx), caudate-putamen (CPU), subthalamic area (STN) and substantia nigra pars reticulata (SNr), before and after the administration of apomorphine (5 mg/Kg ip). The recording sessions lasted at least
S19 80 minutes, 20 before and 60 after apomorphine administation. Signals from artifact-free recordings were analyzed by means of Partial Directed in the frequency Coherence, a technique that allows estimating domain how the information propagates among the structures. In basal condition, 6-OHDA rats showed interactions in the beta band between Cx and basal ganglia whereas no interactions were found for the control animals. Apomorphine administration induced interactions in the low gamma band (40 Hz) in both; control and lesioned rats (mainly between CPU/STN and Cx) while control animals presented a higher degree of interaction. In the high gamma range (80 Hz), lesioned rats presented interactions between CPU STN, STN Cx and CPU Cx, while control rats lost the CPU Cx interaction. 6-OHDA lesion modifies how structures in the motor circuit of the basal ganglia interact in the beta band and determines how interactions are modulated by apomorfine administration. This work has been partially supported by the grant FIS 070034 and by the UTE Proyecto CIMA. S7.4 Effects of different forms of amyloid b-peptide on synaptic function C. Ripoli1 , E. Riccardi1 , R. Piacentini1 , G. Bitan2 , C. Grassi1 Institute of Human Physiology, Catholic University Medical School, Rome, Italy, 2 Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States 1
Introduction: In early stages of Alzheimer’s disease, that precede plaque formation and neuronal death, cognitive deficits are likely the result of synaptic function impairment. The key initiating pathogenic event is the accumulation of neurotoxic aggregates of amyloid b-peptide (Ab) in hippocampus and cortex. We previously demonstrated that the redox state of methionine in position 35 (Met35) plays a critical role in Ab toxicity. Objective: To determine whether oxidation of Met35 also influences Ab synaptotoxicity we investigated the effects of 20-min lasting perfusion with 200 nM AbWT and its oxidized analogues (AbMet35(O) , AbMet35(O2) ) on synaptic transmission and plasticity, and on synaptophysin (Syn) expression. Methods: We performed electrophysiological experiment on hippocampal brain slices and autaptic neurons to study the long-term potentiation (LTP) and synaptic transmission. We also studied Syn density as the ratio between Syn fluorescence intensity and MAP2 labeled area by confocal microscopy. Results: In control slices, 60 min after tetanus fEPSP amplitude (A) and slope (S) were increased by 138% and 132% of baseline, respectively. This potentiation was significantly lower after AbWT treatment (A: +72%; S: +68%; P < 0.001) whereas no changes in LTP were observed in slices exposed to AbMet35(O) . Surprisingly, AbMet35(O2) reduced the synaptic plasticity to the same level as AbWT . In autaptic microcultures, AbWT and AbMet35(O2) significantly reduced the amplitude of EPSCs evoked by action potentials and mEPSC frequency (P < 0.05) whereas AbMet35(O) had no effects on basal synaptic transmission. Finally, AbWT and AbMet35(O2) significantly reduced Syn density while AbMet35(O) did not affect presynaptic terminals. Conclusion: Our results indicate that the chemical state of Met35 plays a key role in Ab- induced: (i) synaptic depression, (ii) inhibition of synaptic plasticity and (iii) alterations in the expression of proteins relevant for the synaptic function. S7.5 Effects of membrane polarisation on velocity recovery cycles of human muscle fibres in-vivo R. Arunachalam1 , D. Allen1 , C.E.G. Moore2 1 Department of Clinical Neurophysiology, Wessex Neurological Centre, Southampton, United Kingdom, 2 Department of Clinical Neurophysiology, Queen Alexandra Hospital, Portsmouth, United Kingdom Introduction: Techniques capable of measuring components of muscle fibre membrane excitability, akin to nerve excitability testing, show promise in understanding muscle pathophysiology. Automated measurement of velocity recovery cycles (VRC) after direct muscle fibre stimulation has recently been developed. The early supernormality (SN10) reflects membrane capacitance; the late supernormality (SN100) reflects T-tubule function [1,2].