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Borjkhani M, Bahrami F, Janahmadi M. Do Opioids Contribute to Pathological Memory Formation? Introducing a Computational Model to Meet the Question. BCN. 2017;
URL: http://bcn.iums.ac.ir/article-1-962-fa.html
Do Opioids Contribute to Pathological Memory Formation? Introducing a Computational Model to Meet the Question. مجله علوم اعصاب پایه و بالینی. 1395;

URL: http://bcn.iums.ac.ir/article-1-962-fa.html


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. 

نوع مطالعه: Original | موضوع مقاله: Computational Neuroscience
دریافت: ۱۳۹۶/۳/۱۷ | پذیرش: ۱۳۹۶/۷/۱۲ | انتشار: ۱۳۹۷/۲/۳۰

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