Mixed-mode oscillations in pyramidal neurons under antiepileptic drug conditions.

Babak V-Ghaffari,M Kouhnavard,Sherif M Elbasiouny

doi:10.1371/journal.pone.0178244

Abstract

Subthreshold oscillations in combination with large-amplitude oscillations generate mixed-mode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductance-based models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under antiepileptic drug conditions (i.e., when persistent sodium current is inhibited). We investigated not only the mathematical properties of MMOs in these neurons, but also the electrophysiological mechanisms that shape spike clustering. Our results show that pyramidal neurons can display two types of MMOs and the magnitude of the slow potassium current determines whether MMOs of type I or type II would emerge. Our results also indicate that slow potassium currents with large time constant have significant impact on generating the MMOs, as opposed to fast inward currents. Our results provide complete characterization of the subthreshold activities in MMOs in pyramidal neurons and provide explanation to experimental studies that showed MMOs of type I or type II in pyramidal neurons under antiepileptic drug conditions.

Highlights

The entorhinal cortex (EC) plays a pivotal role in the generation of theta and gamma rhythms during rapid-eye-movement sleep, memory function, learning, and exploring behaviors in awake animals [1,2,3,4,5]
Incoming information to the hippocampus is mostly transmitted by stellate cells through the prefrontal pathway in layer II of the EC; whereas outgoing information from the hippocampus is transmitted through layer V of the EC
It has been shown that pyramidal neurons in layer V of the EC might contribute to the generation of spontaneous seizures after status epilepticus, to immobility in the awake animal, and to slow-wave sleep [6,7,8,9]

Summary

Introduction

The entorhinal cortex (EC) plays a pivotal role in the generation of theta and gamma rhythms during rapid-eye-movement sleep, memory function, learning, and exploring behaviors in awake animals [1,2,3,4,5]. Morphological studies of layer V have shown that the majority of cells in this layer are pyramidal neurons, which display a robust, rhythmic subthreshold activity similar to stellate cells [2]. It has been shown that pyramidal neurons in layer V of the EC might contribute to the generation of spontaneous seizures after status epilepticus, to immobility in the awake animal, and to slow-wave sleep [6,7,8,9]. In which persistent sodium current (Inap) is inhibited with drugs such as riluzole and phenyton, have interestingly showed that pyramidal neurons still exhibit subthreshold oscillations [4, 11,12,13], which probably contribute to the abnormal firing patterns of pyramidal neurons under antiepileptic drug conditions. The main goal of this study is to investigate the properties of STOs in pyramidal neurons when Inap is inhibited, and to examine the relationship between these subthreshold activities and the firing patterns in pyramidal neurons

Objectives

Methods

Results

Conclusion