Synaptic Conductances during Interictal Discharges in Pyramidal Neurons of Rat Entorhinal Cortex

被引:26
作者
Amakhin, Dmitry V. [1 ]
Ergina, Julia L. [1 ]
Chizhov, Anton V. [1 ,2 ]
Zaitsev, Aleksey V. [1 ]
机构
[1] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, Lab Mol Mechanisms Neural Interact, St Petersburg, Russia
[2] Ioffe Inst, Div Plasma Phys Atom Phys & Astrophys, Computat Phys Lab, St Petersburg, Russia
基金
俄罗斯科学基金会;
关键词
temporal lobe epilepsy; cortico-hippocampal slices; synaptic conductance; NMDA; GABA; AMPA; interictal discharge; SEIZURE-LIKE EVENTS; IN-VITRO; NMDA RECEPTORS; EPILEPTIFORM SYNCHRONIZATION; INTRACELLULAR BLOCKADE; LIMBIC SYSTEM; HIPPOCAMPUS; TRANSITION; INHIBITION; DYNAMICS;
D O I
10.3389/fncel.2016.00233
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In epilepsy, the balance of excitation and inhibition underlying the basis of neural network activity shifts, resulting in neuronal network hyperexcitability and recurrent seizure-associated discharges. Mechanisms involved in ictal and interictal events are not fully understood, in particular, because of controversial data regarding the dynamics of excitatory and inhibitory synaptic conductances. In the present study, we estimated AMPAR-, NMDAR-, and GABA(A) R-mediated conductances during two distinct types of interictal discharge (IID) in pyramidal neurons of rat entorhinal cortex in cortico-hippocampal slices. Repetitively emerging seizure-like events and IIDs were recorded in high extracellular potassium, 4-aminopyridine, and reduced magnesium-containing solution. An original procedure for estimating synaptic conductance during IIDs was based on the differences among the current-voltage characteristics of the synaptic components. The synaptic conductance dynamics obtained revealed that the first type of IID is determined by activity of GABA(A) R channels with depolarized reversal potential. The second type of IID is determined by the interplay between excitation and inhibition, with early AMPAR and prolonged depolarized GABA(A) R and NMDAR-mediated components. The study then validated the contribution of these components to IIDs by intracellular pharmacological isolation. These data provide new insights into the mechanisms of seizures generation, development, and cessation.
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页数:15
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