Switchable slow cellular conductances determine robustness and tunability of network states

Abstract

Neuronal information processing is regulated by fast and localized fluctuations of brain states. Brain states reliably switch between distinct spatiotemporal signatures at a network scale even though they are composed of heterogeneous and variable rhythms at a cellular scale. We investigated the mechanisms of this network control in a conductance-based population model that reliably switches between active and oscillatory mean-fields. Robust control of the mean-field properties relies critically on a switchable negative intrinsic conductance at the cellular level. This conductance endows circuits with a shared cellular positive feedback that can switch population rhythms on and off at a cellular resolution. The switch is largely independent from other intrinsic neuronal properties, network size and synaptic connectivity. It is therefore compatible with the temporal variability and spatial heterogeneity induced by slower regulatory functions such as neuromodulation, synaptic plasticity and homeostasis. Strikingly, the required cellular mechanism is available in all cell types that possess T-type calcium channels but unavailable in computational models that neglect the slow kinetics of their activation.

Cellular switches orchestrate rhythmic circuits

“…In the absence of a slow negative conductance at the cellular level, breaking network symmetry and increasing cellular heterogeneity results in the incapacity to generate any circuit rhythm for most randomly picked parameter sets and neuromodulatory states, even with strong network connectivity. We do not show any quantitative result here, but identical observations are reported in variable circuits and heterogeneous networks in Drion et al, 2018).…”

“…This property is provided for instance by slowly-activating calcium channels. The role of this specific intrinsic property has been extensively studied by the authors in the recent years Franci et al, 2018;Drion et al, 2018). It acts as a switch of excitability for the neuron.…”

Robust switches in thalamic network activity require a timescale separation between sodium and T-type calcium channel activations

“…An external current is exerted on the inhibitory cells (see Figure 4A). This hyperpolarizing current causes a cellular switch and drives the neurons in a synchronous bursting mode as previously shown with the isolated E-I circuit in Figure 2A [Drion et al (2018)]. This change in cellular firing pattern is translated by an oscillatory behavior at the network level.…”

“…Throughout this paper, we compare six well-established conductance-based models of thalamic neurons [Drion, Dethier, Franci, and Sepulchre (2018)] (model 1), [Destexhe, Contreras, Steriade, Sejnowski, and Huguenard (1996)] (model 2), [Destexhe, Neubig, Ulrich, and Huguenard (1998)] (model 3), [Huguenard and McCormick (1992); McCormick and Huguenard (1992)] (model 4), [X. J. Wang (1994)] (model 5) and [Rush and Rinzel (1994)] (model 6).…”

Co-opting evo-devo concepts for new insights into mechanisms of behavioural diversity

“…Similarly, the molecular interactions among signal transduction pathway components determine physiological features such as the alternation between two firing states in hunger-related neurons in the mouse hypothalamus (Yang et al, 2011). Computational models implicate specific calcium channel subtypes in supporting positive feedback necessary for alternative firing patterns (Franci et al, 2018;Drion et al, 2018); hence, specific biochemical changes could tune criticality and adjust neural firing state based on internal or external cues. Understanding how neural circuits adjust criticality more broadly will offer novel insights into the ways in which genetic changes and experience contribute to individual variation in neural system function and behaviour.…”