A mathematical model for neuron astrocytes interactions in hippocampus during addiction

Addiction is a chronic disorder whereby addicted individuals compulsively engage in drug seeking despite its negative consequences. Hippocampus has unavoidable role in addiction because of its importance in learning and memory. Any modification of hippocampal cells alters dopamine levels in NAc and firing rates of VTA dopaminergic cells. In order to have a better understanding of the addiction in cellular level, we present a mathematical model of a tripartite synapse in hippocampus. The proposed model can show some functions of synapses under addiction that may contribute to drug seeking and relapse behaviors. The model is based on glutamate alterations in synaptic cleft during drug abuse. Experimental studies suggest that during drug abuse, NMD AR dependent synaptic transmission is increased. According to our simulation results, dysfunction of astrocyte has a significant role in initiating addiction. Since healthy astrocytes has a comprehensive control over synaptic interactions it may use to treat addicted related behaviors. Also, we may conclude that addiction causes abnormalities on postsynaptic signaling such as NMDA currents. Furthermore, we may suggest that drug induced D-serine enhancement in synaptic cleft potentiate post synaptic calcium influx and LTP.

[1]  Krasimira Tsaneva-Atanasova,et al.  A unified model of CA1/3 pyramidal cells: an investigation into excitability. , 2011, Progress in biophysics and molecular biology.

[2]  Justin W. Kenney,et al.  Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine , 2008, Molecular Neurobiology.

[3]  R. LaLumiere,et al.  Glutamate: the new frontier in pharmacotherapy for cocaine addiction. , 2008, CNS & neurological disorders drug targets.

[4]  H. Schmidt,et al.  Cocaine‐induced neuroadaptations in glutamate transmission , 2010, Annals of the New York Academy of Sciences.

[5]  A. Kelley,et al.  Glutamate‐Mediated Plasticity in Corticostriatal Networks , 2003 .

[6]  Roberto A. Prado-Alcalá,et al.  Nicotine Uses Neuron-Glia Communication to Enhance Hippocampal Synaptic Transmission and Long-term Memory , 2012, PloS one.

[7]  A. Eisch,et al.  Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and stem cell biology , 2006, Hippocampus.

[8]  David Golomb,et al.  Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. , 2006, Journal of neurophysiology.

[9]  P. Kalivas,et al.  Astrocytic Dysfunction and Addiction , 2014, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[10]  E. Cherubini,et al.  Nicotine‐induced enhancement of synaptic plasticity at CA3–CA1 synapses requires GABAergic interneurons in adult anti‐NGF mice , 2006, The Journal of physiology.

[11]  R. J. Brennan,et al.  Nicotine gates long‐term potentiation in the hippocampal CA1 region via the activation of α2* nicotinic ACh receptors , 2007, The European journal of neuroscience.

[12]  Peter Jung,et al.  Astrocytes Optimize the Synaptic Transmission of Information , 2008, PLoS Comput. Biol..

[13]  M. Olive,et al.  Glutamatergic substrates of drug addiction and alcoholism. , 2008, Biochemical pharmacology.

[14]  F. Fumagalli,et al.  Cocaine-induced glutamate receptor trafficking is abrogated by extinction training in the rat hippocampus , 2014, Pharmacological reports : PR.

[15]  E. Ben-Jacob,et al.  Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes , 2009, Journal of biological physics.

[16]  C. Koch,et al.  Methods in Neuronal Modeling: From Ions to Networks , 1998 .

[17]  D. Ji,et al.  Synaptic Plasticity and Nicotine Addiction , 2001, Neuron.

[18]  Kaushik Kumar Majumdar,et al.  A mathematical model of the tripartite synapse: astrocyte-induced synaptic plasticity , 2011, Journal of Biological Physics.

[19]  P. Haydon,et al.  Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. A. Dani,et al.  Nicotinic mechanisms influencing synaptic plasticity in the hippocampus , 2009, Acta Pharmacologica Sinica.

[21]  Li-guang Sun,et al.  Reparatory effects of nicotine on NMDA receptor‐mediated synaptic plasticity in the hippocampal CA1 region of chronically lead‐exposed rats , 2006, The European journal of neuroscience.

[22]  R. Malenka,et al.  Synaptic plasticity and addiction , 2007, Nature Reviews Neuroscience.

[23]  F. Bahrami,et al.  Neurophysiological analysis of schizophrenia based on dysfunction of the glutamatergic system using a tripartite synapse model , 2013, 2013 20th Iranian Conference on Biomedical Engineering (ICBME).

[24]  Lan Ma,et al.  Hippocampal Long-Term Potentiation Is Reduced by Chronic Opiate Treatment and Can Be Restored by Re-Exposure to Opiates , 2002, The Journal of Neuroscience.

[25]  P. Jung,et al.  Stochastic properties of Ca(2+) release of inositol 1,4,5-trisphosphate receptor clusters. , 2002, Biophysical journal.

[26]  E. Vizi,et al.  The effect of nicotine on spiking activity and Ca2+ dynamics of dendritic spines in rat CA1 pyramidal neurons , 2008, Hippocampus.

[27]  H. Markram,et al.  The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. , 1997, Proceedings of the National Academy of Sciences of the United States of America.