Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation

James P Roach,Michal R Zochowski,Leonard M Sander,Eshel Ben-Jacob,Olaf Sporns

doi:10.1371/journal.pcbi.1004449

Abstract

Acetylcholine (ACh) is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA) and a shift in the phase response curve (PRC). We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS) differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh) patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh), traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

Highlights

The difference between cortical activity patterns during waking, rapid eye movement sleep (REM), and slow wave sleep (SWS) is striking
A classic example of this is the transition from high frequency to low frequency
Formation of Waves in a Cortical Model had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Summary

Introduction

The difference between cortical activity patterns during waking, rapid eye movement sleep (REM), and slow wave sleep (SWS) is striking. The functional role of high frequency local activation (i.e. waking or REM state) has been linked to attention and working memory [3,4,5], while traits of SWS have been related to synaptic homeostasis and sleep pressure [2, 6,7,8] Both of these dynamic patterns can be thought of as upstates, but with differing lengths. The nicotinic receptor directly depolarizes cells while the muscarinic suppresses voltage-gated potassium channels Inactivation of these channels, and the current associated with them (the M-current), changes the intrinsic excitability of neurons. It has been previously shown that networks of type 1 neurons are asynchronous while those of type 2 neurons are highly synchronous [12]

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