Mean field model of acetylcholine mediated dynamics in the cerebral cortex

Abstract

A recent continuum model of the large scale electrical activity of the cerebral cortex is generalized to include cholinergic modulation. In this model, dynamic modulation of synaptic strength acts over the time scales of nicotinic and muscarinic receptor action. The cortical model is analyzed to determine the effect of acetylcholine (ACh) on its steady states, linear stability, spectrum, and temporal responses to changes in subcortical input. ACh increases the firing rate in steady states of the system. Changing ACh concentration does not introduce oscillatory behavior into the system, but increases the overall spectral power. Model responses to pulses in subcortical input are affected by the tonic level of ACh concentration, with higher levels of ACh increasing the magnitude firing rate response of excitatory cortical neurons to pulses of subcortical input. Numerical simulations are used to explore the temporal dynamics of the model in response to changes in ACh concentration. Evidence is seen of a transition from a state in which intracortical inputs are emphasized to a state where thalamic afferents have enhanced influence. Perturbations in ACh concentration cause changes in the firing rate of cortical neurons, with rapid responses due to fast acting facilitatory effects of nicotinic receptors on subcortical afferents, and slower responses due to muscarinic suppression of intracortical connections. Together, these numerical simulations demonstrate that the actions of ACh could be a significant factor modulating early components of evoked response potentials.

Mean field model of acetylcholine mediated dynamics in the thalamocortical system

“…In addition, it is very difficult to fit an ERP model to components later than 300 ms post-stimulus using static gains (Kerr et al, 2008;Rennie et al, 2002), so the dynamic gains provided by cholinergic neuromodulation may help in this regard. In a recent cortical model of ACh mediated dynamics (Clearwater et al, 2007), it was shown that ACh is capable of increasing the response of cortical neurons to subcortical inputs, similarly to the increase in N100 size noted in ERP literature (Coull, 1998).…”

“…In our cortical model (Clearwater et al, 2007) it was found that only one steady state existed for physiologically realistic parameter values, and that the steady-state firing rates of cortical neurons increased with increased ½ACh ð0Þ (note that we use X ð0Þ to denote the steady-state value of variable X).…”

“…The values for all N ab and s ab , the rate constants a and b, y a , s a ; r e;i;s ; Q max a ; v a and t 0 are taken from Robinson et al (2004), and a comprehensive survey of physiologic and model-based constraints on these values can be found in the results section of that paper. The values for parameters m ab and l ab are taken from Clearwater et al (2007) and a discussion on the physiological basis for these values can be found in Section 2.2 of that paper. Parameters k and s 1 ab are introduced in this model, their values are based on physiological recordings and are discussed below.…”

“…Consequently, the effects of ACh on cortical activity are diverse. In previous work (Clearwater et al, 2007) we generalized a cortical model of neural dynamics (Rennie et al, 2000;Robinson et al, 1997Robinson et al, , 1998aRobinson et al, , 2004 to include cholinergic neuromodulation. Here we continue this analysis with a thalamocortical system that incorporates the major actions of cortical ACh.…”

“…Nominal parameter values for the thalamocortical model, with all values apart from s 1 ab and k taken fromRobinson et al (2004) andClearwater et al (2007) ib for b ¼ e; i; s. We obtained our k value by fitting Eq. (11) to Figs.…”