During locomotion, visual cortical neurons fire at higher rates to visual stimuli than during immobility while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons as well as from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, while noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.

Typical absence has long been considered as the prototypic form of generalized nonconvulsive epileptic seizures. Recent investigations in patients and animal models suggest that absence seizures could originate from restricted regions of the cerebral cortex. However, the cellular and local network processes of seizure initiation remain unknown. Here, we show that absence seizures in Genetic Absence Epilepsy Rats from Strasbourg, a well established genetic model of this disease, arise from the facial somatosensory cortex. Using in vivo intracellular recordings, we found that epileptic discharges are initiated in layer 5/6 neurons of this cortical region. These neurons, which show a distinctive hyperactivity associated with a membrane depolarization, lead the firing of distant cortical cells during the epileptic discharge. Consistent with their ictogenic properties, neurons from this "focus" exhibit interictal and preictal oscillations that are converted into epileptic pattern. These results confirm and extend the "focal hypothesis" of absence epilepsy and provide a cellular scenario for the initiation and generalization of absence seizures.

Absence seizures consist of bilateral spike-and-wave discharges (SWDs) occurring over widespread cortical and thalamic regions. In genetic models of absence epilepsy, recent in vivo investigations indicate that SWDs emerge first in the facial somatosensory cortex and then propagate via the corticothalamocortical loop. The specific involvement of this cortical region in ictogenic processes remained to be established and the participation of its related thalamocortical system in seizure initiation remained unclear. Here, using electrocorticographic (ECoG) and intracellular recordings in vivo from cortex and thalamus in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS), we obtained novel evidence for the cortical focus theory of absence epilepsy. We report that blockade of action potential discharge and synaptic activities in facial somatosensory cortical neurons, by topical application of tetrodotoxin, prevents the occurrence of paroxysmal activities in local and distant cortical neurons and ECoGs, as well as in thalamocortical neurons in register with the somatosensory cortex. In contrast, pharmacological inhibition of a remote motor cortical region or of the related thalamic nuclei did not suppress ictal activities in the somatosensory cortex. This study demonstrates that SWDs in GAERS have a focal origin within the facial somatosensory cortex, which is sufficient and necessary to generate ictal activities.