A novel, oprogenetic instant epilepsy model targeting the cortothalamic system
Thalamocortical circuits, a reciprocal connection between cortical areas and their functionally corresponding thalamic nuclei, play an important role in sensory perception and the generation of sleep rhythms, but also participate in certain pathological processes. Here we present a novel instant epilepsy model, based on optogenetic activation of corticothalamic (CT) feedback from layer 6 of the cortex to the thalamus. We used NTSR1-ChR mice, where channelrhodopsin-2 is expressed exclusively in thalamically projecting layer 6 pyramidal cells. In almost all cases, 8 Hz stimulation for 10‑20 seconds in somatosensory cortex induced epileptic seizures in healthy, non‑epileptic animals. The activity showed the characteristics of typical tonic-clonic seizures. Seizures were elicited by activating the somata of CT cells in primary somatosensory cortex, or the axon terminals of the same population in somatosensory thalamus. To determine, if the phenomenon was specific to the somatosensory cortex, we used the same stimulation in visual and auditory cortices, where we could trigger similar seizures. Finally, we wanted to know, whether the seizure induction is due to some resonant property of the network. Several frequencies between 4 and 30 Hz also induced epileptic seizures, albeit with lower efficacy. We have found no difference between the evocability of seizures during the awake and sleep states so far. Based on these results, our instant epilepsy model seems suitable for researching these circuits via repeatedly evoked epileptic seizures. In further experiments, we are planning to establish whether the spread of the seizure is dependent on the thalamic or on the cortical circuitry.