Synaptic connections shape physiological and pathological thalamic oscillations

Written by Bús Bálint, Antal Károly, Emri Zsuzsa

Thalamic cells maintain several types of physiological and pathological oscillations. The most widely studied pathological thalamic activity is the spike and wave discharge, a 3–4 Hz oscillation emerging synchronously in thalamic and cortical areas during absence seizures. The contribution of different voltage- and ligand-gated currents to this activity is well characterized, while the role of intrathalamic connections in shaping this activity is less understood, since experimental reorganization of these connections is difficult. Therefore we used a realistic computer model of 30 thalamocortical and 30 reticular neurons in the NEURON modeling environment and by changing the ratio and topography of inhibitory and excitatory inputs we revealed mechanisms transforming the physiological spindle activity to a pathological 3–4 Hz oscillation. Genetic modifications leading to absence epilepsy showed that decreased inhibition among reticular neurons and increased inhibition of thalamocortical cells supported the development of continuous 3–4 Hz oscillation. Our model reproduced these results and also showed that the transformation depended not only on the ratio of inhibitory and excitatory contacts but also on their topography. Grouping the reticular cells that did not receive intrareticular inhibition maintained spindle oscillation while grouping thalamocortical cells receiving strong reticular inhibition had the opposite effect, it helped the development of 3–4 Hz oscillation. Our model not only reproduced experimental results but also predicted a critical role of intrathalamic connections in the maintenance of thalamic oscillations.


Keywords: absence epilepsy, GABAerg input, nucleus reticularis thalami, spindle oscillation, thalamocortical cell

Print   Email