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1- CIPCE, Motor Control and Computational Neuroscience Laboratory, School of ECE, University College of Engineering, University of Tehran, Tehran, Iran
2- PhD. CIPCE, Motor Control and Computational Neuroscience Laboratory, School of ECE, University College of Engineering, University of Tehran, Tehran, Iran
3- Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:  

Introduction: Opioids hijack learning and memory formation mechanisms of brain and induce a pathological memory in the hippocampus. This effect is mainly mediated by modifications in glutamatergic system. Speaking more precisely, Opioids presence in a synapse inhibits blockage of N-methyl-D-aspartate receptor (NMDAR) by Mg2+ and enhances conductance of NMDAR and thus, induces false LTP.  

Methods: Based on experimental observations of different researchers, we developed a mathematical model for a pyramidal neuron of the hippocampus to study this false LTP. The model contains a spine of the pyramidal neuron with NMDAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), and Voltage-Gated Calcium Channels (VGCCs). The model describes also Calmodulin-dependent protein kinase II (CaMKII) and AMPAR phosphorylation processes which are assumed to be the indicators of Long-Term Potentiation (LTP) induction in the synapse.

Results: Simulation results indicate that the effect of inhibition of Mg2+ blockage of NMDARs by on the false LTP is not as crucial as the effect of NMDAR's conductance modification by opioids. We also observed that activation of VGCCs has a dominant role in inducing pathological LTP.  

Discussion: Moreover, our results confirm that preventing this pathological LTP is possible by three different mechanisms: 1) by decreasing NMDAR's conductance, 2) by attenuating VGCC's mediated current, and 3) by enhancing glutamate clearance rate from the synapse. 

Type of Study: Original | Subject: Computational Neuroscience
Received: 2017/06/7 | Accepted: 2017/10/4 | Published: 2018/05/20

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