The antipsychotic drugs olanzapine and haloperidol modify network connectivity and spontaneous activity of neural networks in vitro.

作者: Egor Dzyubenko , Georg Juckel , Andreas Faissner

DOI: 10.1038/S41598-017-11944-0

关键词:

摘要: Impaired neural synchronization is a hallmark of psychotic conditions such as schizophrenia. It has been proposed that schizophrenia-related cognitive deficits are caused by an unbalance reciprocal inhibitory and stimulatory signaling. This supposedly leads to decreased power induced gamma oscillations during the performance tasks. In light this hypothesis efficient antipsychotic treatment should modify connectivity local circuits. To address issue, we investigated model hippocampal neuronal networks in vitro. Inhibitory excitatory innervation GABAergic glutamatergic neurons was quantified using immunocytochemical markers automated routine estimate network connectivity. The first generation (FGA) second (SGA) drugs haloperidol olanzapine, respectively, differentially modified density synaptic inputs. Based on observed synapse modifications, developed computational reliably predicted distinct changes activity patterns. results modeling were confirmed spontaneous measurements multiple electrode array (MEA) technique. When cultures treated with overall increased, whereas had opposite effect. We conclude FGAs SGAs affect balance between inhibition excitation networks.

参考文章(55)
Thomas Voigt, Thoralf Opitz, Ana D. de Lima, Synchronous oscillatory activity in immature cortical network is driven by GABAergic preplate neurons. The Journal of Neuroscience. ,vol. 21, pp. 8895- 8905 ,(2001) , 10.1523/JNEUROSCI.21-22-08895.2001
Sung Woo Park, Chan Hong Lee, Hye Yeon Cho, Mi Kyoung Seo, Jung Goo Lee, Bong Ju Lee, Wongi Seol, Baik Seok Kee, Young Hoon Kim, None, Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures. Synapse. ,vol. 67, pp. 224- 234 ,(2013) , 10.1002/SYN.21634
Egor Dzyubenko, Christine Gottschling, Andreas Faissner, Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets Neural Plasticity. ,vol. 2016, pp. 5214961- 5214961 ,(2016) , 10.1155/2016/5214961
S. Mennerick, J. Que, A. Benz, C. F. Zorumski, Passive and synaptic properties of hippocampal neurons grown in microcultures and in mass cultures. Journal of Neurophysiology. ,vol. 73, pp. 320- 332 ,(1995) , 10.1152/JN.1995.73.1.320
Colenso M. Speer, Hazen P. Babcock, Xiaowei Zhuang, Yaron M. Sigal, Mapping Synaptic Input Fields of Neurons with Super-Resolution Imaging Cell. ,vol. 163, pp. 493- 505 ,(2015) , 10.1016/J.CELL.2015.08.033
L. M. Grover, E. Kim, J. D. Cooke, W. R. Holmes, LTP in Hippocampal Area CA1 Is Induced by Burst Stimulation over a Broad Frequency Range Centered around Delta. Learning & Memory. ,vol. 16, pp. 69- 81 ,(2009) , 10.1101/LM.1179109
Maren Geissler, Andreas Faissner, A new indirect co-culture set up of mouse hippocampal neurons and cortical astrocytes on microelectrode arrays. Journal of Neuroscience Methods. ,vol. 204, pp. 262- 272 ,(2012) , 10.1016/J.JNEUMETH.2011.11.030
H.M. Critchlow, P.R. Maycox, J.N. Skepper, O. Krylova, Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons. Molecular and Cellular Neuroscience. ,vol. 32, pp. 356- 365 ,(2006) , 10.1016/J.MCN.2006.05.007
Chia-Ling Chang, Thorsten Trimbuch, Hsiao-Tuan Chao, Julia-Christine Jordan, Melissa A. Herman, Christian Rosenmund, Investigation of Synapse Formation and Function in a Glutamatergic-GABAergic Two-Neuron Microcircuit The Journal of Neuroscience. ,vol. 34, pp. 855- 868 ,(2014) , 10.1523/JNEUROSCI.0229-13.2014
H. Liu, C. Dean, C. P. Arthur, M. Dong, E. R. Chapman, Autapses and networks of hippocampal neurons exhibit distinct synaptic transmission phenotypes in the absence of synaptotagmin I. The Journal of Neuroscience. ,vol. 29, pp. 7395- 7403 ,(2009) , 10.1523/JNEUROSCI.1341-09.2009