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

Dmitry V Amakhin; Julia L Ergina; Anton V Chizhov; Aleksey V Zaitsev

doi:10.3389/fncel.2016.00233

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

Front Cell Neurosci. 2016 Oct 13:10:233. doi: 10.3389/fncel.2016.00233. eCollection 2016.

Authors

Dmitry V Amakhin¹, Julia L Ergina¹, Anton V Chizhov², Aleksey V Zaitsev¹

Affiliations

¹ Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences Saint Petersburg, Russia.
² Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesSaint Petersburg, Russia; Computational Physics Laboratory, Division of Plasma Physics, Atomic Physics and Astrophysics, Ioffe InstituteSaint Petersburg, Russia.

Abstract

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.

Keywords: AMPA; GABA; NMDA; cortico-hippocampal slices; interictal discharge; synaptic conductance; temporal lobe epilepsy.