Data-driven modeling of cholinergic modulation of neural microcircuits: bridging neurons, synapses, and network states

Abstract

1Neuromodulators, such as acetylcholine (ACh), control information processing in neural microcircuits by regulating neuronal and synaptic physiology. Computational models and simulations enable predictions on the potential role of ACh in reconfiguring network states. As a prelude into investigating how the cellular and synaptic effects of ACh collectively influence emergent network dynamics, we developed a data-driven framework incorporating phenomenological models of the anatomy and physiology of cholinergic modulation of the neocortex. The first-draft models were integrated into a biologically detailed tissue model of neocortical microcircuitry to predict how ACh affects different types of neurons and synapses, and consequently alters global network states. Preliminary simulations not only corroborate the long-standing notion that ACh desynchronizes network activity, but also reveal a potentially finegrained control over a spectrum of neocortical states. We show that low levels of ACh, such as those during sleep, drive microcircuit activity into slow oscillations and network synchrony, whereas high ACh concentrations, such as those during wakefulness, govern fast oscillations and network asynchrony. In addition, network states modulated by ACh levels shape spike-time cross-correlations across distinct neuronal populations in strikingly different ways. These effects are likely due to the differential regulation of neurons and synapses caused by increasing levels of ACh that enhances cellular excitability by increasing neuronal activity and decreases the efficacy of local synaptic transmission by altering neurotransmitter release probability. We conclude by discussing future directions to refine the biological accuracy of the framework, which will extend its utility and foster the development of hypotheses to investigate the role of neuromodulation in neural information processing.