Intrathalamic Connections Shape Spindle Activity \u2014 A Modelling Study

Abstract

Spindle oscillations are generated predominantly during sleep state II, through cyclical interactions between thalamocortical and reticular neurons. Inhibition from reticular cells is critical for this activity; it enables burst fring by the de-inactivation of T-type Ca2+ channels. While the effect of different channelopathies on spindling is extensively investigated, our knowledge about the role of intrathalamic connections is limited. Therefore, we explored how the connection pattern and the density of reticular inhibitory synapses affect spindle activity in a thalamic network model. With more intrareticular connections, synchronous fring of reticular cells, and intraspindle burst frequency decreased, spindles lengthened. In models with strong intrareticular inhibition spindle activity was impaired, and a sustained 6–8 Hz oscillation was generated instead. The strength of reticular innervation onto thalamocortical cells played a key role in the generation of oscillations; it determined the amount of thalamocortical cell bursts, and consequently spindle length. Focal inputs supported bursts but affected only a few cells thus barely reinforced network activity, while diffuse contacts aided bursts only when a suffcient number of reticular cells fred synchronously. According to our study, alterations in the connection pattern infuence thalamic activities and may contribute to pathological conditions, or alternatively, they serve as a compensatory mechanism.