Persistent firing in LEC III neurons is differentially modulated by learning and aging.

Carmen Lin,John F Disterhoft,Venus N Sherathiya,M Matthew Oh

doi:10.7554/elife.56816

Abstract

Whether and how persistent firing in lateral entorhinal cortex layer III (LEC III) supports temporal associative learning is still unknown. In this study, persistent firing was evoked in vitro from LEC III neurons from young and aged rats that were behaviorally naive or trained on trace eyeblink conditioning. Persistent firing ability from neurons from behaviorally naive aged rats was lower compared to neurons from young rats. Neurons from learning impaired aged animals also exhibited reduced persistent firing capacity, which may contribute to aging-related learning impairments. Successful acquisition of the trace eyeblink task, however, increased persistent firing ability in both young and aged rats. These changes in persistent firing ability are due to changes to the afterdepolarization, which may in turn be modulated by the postburst afterhyperpolarization. Together, these data indicate that successful learning increases persistent firing ability and decreases in persistent firing ability contribute to learning impairments in aging.

Highlights

Persistent firing is the ability of a neuron to continuously fire action potentials even after the termination of a triggering stimulus
To determine whether aging decreased persistent firing ability in layer III (LEC III) neurons, persistent firing was evoked in neurons from behaviorally naive young adult (Young Naive – YN) and aged (Aged Naive – AN) male rats based on protocols previously described (Tahvildari et al, 2007; Tahvildari et al, 2008; Yoshida et al, 2008; Batallan-Burrowes and Chapman, 2018)
To ensure that differences in probability were not due to differences in the number of action potentials evoked during the current injection, the neurons were injected with a 2 s long train of 2 ms, 2 nA current pulses at 20 Hz to elicit a total of 40 action potentials to evoke persistent firing (Figure 1C)

Summary

Introduction

Persistent firing is the ability of a neuron to continuously fire action potentials even after the termination of a triggering stimulus. Evidence that persistent firing may support temporal associative learning comes from an in vivo study of prefrontal neurons, which showed elevated activity during the delay period of a working memory task (Fuster, 1972). Within the LEC, layers III and V pyramidal neurons have been shown to be capable of persistent firing (Tahvildari et al, 2007; Tahvildari et al, 2008). Persistent firing by layer III LEC pyramidal neurons is a prime candidate to support temporal associative learning. How this may occur is yet to be determined

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