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Mechanisms underlying persistent activity in a model PFC microcircuit

PFC neurons provide the means to establish behavioral continuity over time by sustaining their firing rate throughout the delay period during working memory tasks. So far, synaptic reverberation has been proposed to underlie the persistent activity, through recurrent excitation, within a homogenous network [1]. However, electrophysiological data suggest that the pyramidal network that supports this activity exhibits biophysical heterogeneity [2]. The goal of this study is to incorporate such biophysical data in a compartmental network model of layer V PFC neurons and investigate the role of cellular mechanisms in supporting persistent activity. Toward this goal, we developed a microcircuit containing both pyramidal and interneuron models of layer V PFC cells. The pyramidal neuron model is implemented in the NEURON simulation environment [3] and is morphologically simplified; it includes modeling equations for 15 types of ionic mechanisms, known to be present in these neurons and is validated against experimental data [4]. The interneuron model is a previously published basket-type fast spiking neocortical interneuron [5]. The microcircuit contains a single interneuron and four pyramidal cells and is fully connected through recurrent connections. The connectivity properties of the network (type/location of synapses) were based on experimental anatomical and electrophysiological data [6], in an effort to simulate a microcolumn of layer V pyramidal neurons in the PFC. The microcircuit was used to investigate the stimulation protocol as well as the biophysical makeup required for the sustained firing. The specific contribution of both intrinsic (the calcium activated non-selective cation (CAN) current) and synaptic (the NMDA receptor) mechanisms that have previously been suggested to partake a role in persistent firing [4, 7] was examined. Simulations revealed that persistent activity at physiological frequencies could emerge in the microcircuit throughout a physiological range of NMDA-to-AMPA current ratios [8]. Furthermore, activation of the CAN current modulated the properties (firing frequency distribution) of this sustained activity. In summary, preliminary results show that our microcircuit is capable of supporting persistent activity resulting from the interaction of intrinsic ionic mechanisms and synaptic input. We further suggest that intrinsic mechanisms of pyramidal neurons may counteract the limiting effect of heterogeneity in PFC networks. On going simulations aim to dissect the roles of CAN and NMDA mechanisms in the emergence and maintenance of persistent activity in layer V of PFC, as well as the ability of a second stimulus to modulate the properties of persistent activity.

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Acknowledgements

This work was supported by EMBO Young Investigator Program (PP), an IKY postdoctoral fellowship (KS), and Maria Michail Manasaki-University of Crete scholarship (AP).

Author information

Correspondence to Athanasia Papoutsi.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Pyramidal Neuron
  • Persistent Activity
  • Sustained Firing
  • Recurrent Excitation
  • Layer Versus Pyramidal Neuron