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

Abstract

Switches in brain states, synaptic plasticity and neuromodulation are fundamental processes in our brain that take place concomitantly across several spatial and timescales. All these processes target neuron intrinsic properties and connectivity to achieve specific physiological goals, raising the question of how they can operate without interfering with each other. Here, we highlight the central importance of a timescale separation in the activation of sodium and T-type calcium channels to sustain robust switches in brain states in thalamic neurons that are compatible with synaptic plasticity and neuromodulation. We quantify the role of this timescale separation by comparing the robustness of rhythms of six published conductance-based models at the cellular, circuit and network levels. We show that robust rhythm generation requires a T-type calcium channel activation whose kinetics are situated between sodium channel activation and T-type calcium channel inactivation in all models despite their quantitative differences.

Investigation of CACNA1I Cav3.3 Dysfunction in Hemiplegic Migraine

“…Robust rhythm generation in the thalamus requires timely activation of T-type channels to stimulate the sodium channel activation and is imperative to processes such as synaptic plasticity in thalamic neurons ( Jacquerie and Drion, 2021 ). The physiological role of thalamic neurons I w and its contribution to the activities of other neuronal types underlines the importance of alterations in T-type channel function in neurological and psychiatric disorders ( Crunelli et al, 2005 ).…”

Switches to slow rhythmic neuronal activity lead to a plasticity-induced reset in synaptic weights

“…We then added some variability in order to grow closer to what is observed in biological systems [1,[39][40][41][42]. To this end, ten circuits varying in their parameter sets of maximal intrinsic conductances and applied currents were simulated.…”

“…All neurons are modeled using a single-compartment Hodgkin and Huxley formalism. The membrane voltage V m evolves as follows (Drion et al, 2018;Jacquerie and Drion, 2021):…”

“…Our brain has the ability to process information to quickly analyze or react to incoming events from the environment, as well as to learn from experience to shape our memory. This information processing is built on fluctuations in rhythmic neuronal patterns at the cellular and population levels, each defining brain states [1][2][3]. These patterns are spatiotemporal signatures of large neuronal populations.…”

“…These patterns are spatiotemporal signatures of large neuronal populations. The switches between different brain states can be fast and localized, as observed for instance in brain areas prior to movement initiation [4], or global and long-lasting, such as those characterizing wake-sleep cycles [1, 5, 6]. These rhythms translate the collective activity of neurons interconnected via synaptic connections.…”