Seizure-Induced Potentiation of AMPA Receptor-Mediated Synaptic Transmission in the Entorhinal Cortex

被引:29
作者
Amakhin, Dmitry V. [1 ]
Soboleva, Elena B. [1 ]
Ergina, Julia L. [1 ]
Malkin, Sergey L. [1 ]
Chizhov, Anton V. [1 ,2 ]
Zaitsev, Aleksey V. [1 ,3 ]
机构
[1] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, Lab Mol Mech Neural Interact, St Petersburg, Russia
[2] Russian Acad Sci, Ioffe Inst, St Petersburg, Russia
[3] Almazov Natl Med Res Ctr, Inst Expt Med, St Petersburg, Russia
基金
俄罗斯科学基金会;
关键词
temporal lobe epilepsy; calcium-permeable AMPA receptor; epileptiform activity; entorhinal cortex; seizure-like event; synaptic plasticity; CALCIUM-PERMEABLE AMPA; CA1 PYRAMIDAL NEURONS; STATUS EPILEPTICUS; INTRACELLULAR CHLORIDE; GABAERGIC INHIBITION; EXCITATORY SYNAPSES; RAT-BRAIN; GLUTAMATE; SYNCHRONIZATION; POTASSIUM;
D O I
10.3389/fncel.2018.00486
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Excessive excitation is considered one of the key mechanisms underlying epileptic seizures. We investigated changes in the evoked postsynaptic responses of medial entorhinal cortex (ERC) pyramidal neurons by seizure-like events (SLEs), using the modified 4-aminopyridine (4-AP) model of epileptiform activity. Rat brain slices were perfused with pro-epileptic solution contained 4-AP and elevated potassium and reduced magnesium concentration. We demonstrated that 15-min robust epileptiform activity in slices leads to an increase in the amplitude of alpha-amino-3-hydroxy-5methyl- 4-isoxazolepropionic acid receptor (AMPAR)-mediated component of the evoked response, as well as an increase in the polysynaptic gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptor-mediated components. The increase in AMPA-mediated postsynaptic conductance depends on NMDA receptor activation. It persists for at least 15 min after the cessation of SLEs and is partly attributed to the inclusion of calcium-permeable AMPA receptors in the postsynaptic membrane. The mathematical modeling of the evoked responses using the conductance-based refractory density (CBRD) approach indicated that such augmentation of the AMPA receptor function and depolarization by GABA receptors results in prolonged firing that explains the increase in polysynaptic components, which contribute to overall network excitability. Taken together, our data suggest that AMPA receptor enhancement could be a critical determinant of sustained status epilepticus (SE).
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页数:21
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