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

Frontiers in Cellular Neuroscience

Aleksey V. Zaitsev¹  Anton V. Chizhov²  Sergey L. Malkin³  Dmitry V. Amakhin³  Elena B. Soboleva³  Julia L. Ergina³ 

[1] Institute of Experimental Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russia;Ioffe Institute, Russian Academy of Sciences, Saint Petersburg, Russia;Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russia;

关键词: temporal lobe epilepsy;    calcium-permeable AMPA receptor;    epileptiform activity;    entorhinal cortex;    seizure-like event;    synaptic plasticity;   

DOI  :  10.3389/fncel.2018.00486

来源: DOAJ

【 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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated component of the evoked response, as well as an increase in the polysynaptic γ-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).

【 授权许可】

Unknown