Parvalbumin (PV)-expressing interneurons exert power inhibitory effects on the normal cortical network, thus optogenetic activation of PV-interneurons may also possess antiepileptic properties. To investigate this possibility we expressed channel rhodopsin 2 in PV-interneurons by locally injecting the Cre-dependent viral vector AAV2/1-EF1a-DIO-ChETA-EYFP into the S1 barrel cortex of PV-Cre mice. Approximately 3-4 weeks later recurrent seizures were evoked by local application of the chemoconvulsant 4-aminopyridine (4-AP); the ECoG and unit activity were monitored using extracellular silicone electrodes; and PV-interneurons were activated optogenetically during the ictal and inter-ictal phases. Five to ten (5-10) second optogenetic activation of PV-interneurons applied during seizures (ictal phase) terminated 33.7% of seizures compared to only 6% during sham stimulation, and the average seizure duration shortened by 38.7±34.2% compared to sham stimulation. In contrast, inter-ictal optogenetic activation of PV-interneurons showed powerful and robust ictogenic effects. Approximately 60% of inter-ictal optogenetic stimuli resulted in seizure initiation. Single unit recordings revealed that presumptive PV-expressing interneurons markedly increased their firing during optogenetic stimulation, while many presumptive excitatory pyramidal neurons showed a biphasic response with initial suppression of firing during the optogenetic pulse, followed by a synchronized rebound increase in firing at the end of the laser pulse. Our findings indicated that Ictal activation of PV-expressing interneurons possess antiepileptic properties probably due to suppression of firing in pyramidal neurons during the laser pulse. However, in addition inter-ictal activation of PV-expressing interneurons possess powerful ictogenic properties, probably due to synchronized post inhibition rebound firing of pyramidal neurons.
- Copyright © 2015, Journal of Neurophysiology