Intracellular activity of cortical and thalamic neurones during high-voltage rhythmic spike discharge in Long-Evans rats in vivo

摘要

Spontaneous high-voltage rhythmic spike (HVRS) discharges at 6–12 Hz have been widely described in the electrocorticogram (EcoG) of Long-Evans rats. These ECoG oscillations have been proposed to reflect a state of attentive immobility allowing the optimization of sensory integration within the corticothalamic pathway. This hypothesis has been challenged by recent studies emphasizing similarities between HVRS discharges and spike-and-wave discharges (SWDs) in well-established rat genetic models of absence epilepsy. Here, we made in vivo intracellular recordings to determine, for the first time, the cellular mechanisms responsible for the synchronized oscillations in the corticothalamic loop during HVRS discharges in the Long-Evans rats. We show that HVRS discharges are associated in corticothalamic neurones with rhythmic suprathreshold synaptic depolarizations superimposed on a tonic hyperpolarization, likely due to a process of synaptic disfacilitation. Simultaneously, thalamocortical neurones exhibit a large-amplitude ‘croissant’-shaped membrane hyperpolarization with a voltage sensitivity suggesting a potassium-dependent mechanism. This thalamic hyperpolarizing envelope was associated with a membrane oscillation resulting from interactions between excitatory synaptic inputs, a chloride-dependent inhibitory conductance and voltage-gated intrinsic currents. These cortical and thalamic cellular mechanisms underlying HVRS activity in Long-Evans rats are remarkably similar to those previously described in the thalamocortical networks during SWDs. Thus, the present study provides an additional support to the hypothesis that HVRS activity in Long-Evans rats is an absence-like seizure activity.