A robust in vivo-like persistent firing supported by a hybrid of intracellular and synaptic mechanisms.

Arthur Jochems,Motoharu Yoshida,Gennady Cymbalyuk

doi:10.1371/journal.pone.0123799

Abstract

Persistent firing is believed to support short-term information retention in the brain. Established hypotheses make use of the recurrent synaptic connectivity to support persistent firing. However, this mechanism is known to suffer from a lack of robustness. On the other hand, persistent firing can be supported by an intrinsic cellular mechanism in multiple brain areas. However, the consequences of having both the intrinsic and the synaptic mechanisms (a hybrid model) on persistent firing remain largely unknown. The goal of this study is to investigate whether a hybrid neural network model with these two mechanisms has advantages over a conventional recurrent network based model. Our computer simulations were based on in vitro recordings obtained from hippocampal CA3 pyramidal cells under cholinergic receptor activation. Calcium activated non-specific cationic (CAN) current supported persistent firing in the Hodgkin-Huxley style cellular models. Our results suggest that the hybrid model supports persistent firing within a physiological frequency range over a wide range of different parameters, eliminating parameter sensitivity issues generally recognized in network based persistent firing. In addition, persistent firing in the hybrid model is substantially more robust against distracting inputs, can coexist with theta frequency oscillations, and supports pattern completion.

Highlights

Behavioral studies indicate involvement of the prefrontal cortex and medial temporal lobe (MTL) during memory tasks that require short-term (200ms 2013 30s) information retention [1,2,3,4]
Fundamental questions still remain to be elucidated: Can the hybrid model 1) support persistent firing with a frequency observed in vivo, 2) allow persistent firing to co-exist with theta oscillations, 3) reduce parameter sensitivity of persistent firing, and 4) support pattern completion? In this study, we addressed these using neural network models with conductance based spiking neuron models which are carefully tuned to mimic the in vitro recordings
We have recently reported that pyramidal cells in the hippocampal CA3 area support persistent firing through an intrinsic cellular mechanism in the presence of a cholinergic agonist carbachol [30]

Summary

Introduction

Behavioral studies indicate involvement of the prefrontal cortex and medial temporal lobe (MTL) during memory tasks that require short-term (200ms 2013 30s) information retention [1,2,3,4]. Electrophyiological recordings during these memory tasks indicate that persistent firing (a continuous firing of subset of neurons for the duration of the memory maintenance) may underly short-term information retention in the hippocampus [5,6], entorhinal cortex [7] and prefrontal cortex [8,9,10,11]. Cholinergic receptor activation is crucial in tasks that require shortterm information retention [12,13,14].

Objectives

Methods

Results

Discussion

Conclusion