Periodicity of Thalamic Synchronized Oscillations: the Role of Ca2+-Mediated Upregulation of Ih

AbstractThalamocortical networks can generate both normal and abnormal patterns of synchronized network activity, such as spindle waves and spike-and-wave seizures. These periods of synchronized discharge are often separated by a silent, refractory phase of between 5 and 20 s. In vitro investigations have demonstrated that this refractory period is due in large part to the persistent activation of the hyperpolarization-activated cation current Ih in thalamocortical cells. Here, we show that increases in [Ca2+]i due to rebound Ca2+ bursts result in persistent activation of Ih resulting from a positive shift in the activation curve of this current. The dynamical upregulation and persistent activation of Ih is the critical determinant of the time course of the refractory period. These findings demonstrate that periodicity in neural network oscillations may be generated through an interaction between the electrophysiological properties and intracellular signaling pathways of the constituent neurons