Abstracts

Rationale: Epilepsy is a neurological disorder that affects roughly 1% of the population worldwide. Although effective treatments with antiepileptic drugs are available, more than 20% of patients have seizures that are refractory to medical therapy and many patients experience adverse effects. Hence, there is a continued need for novel therapies for those patients. Recently, neuromodulations with the optogenetics toolbox have already been shown to be somewhat effective at treating seizures in animal models of epilepsy and may offer a new hope for these refractory patients. However, more studies showed that optogenetics in seizure control must be carefully considered to avoid its potential negative effects. Here, we combined local field potential recordings and optogenetics to test the function of optogenetic silencing in the acute epileptic model. Methods: We stereotaxically injected the eNpHR3.0 or Jaws AAV viral vector with CaMKII promoter into neocortex of adult mouse to inhibit cortical pyramidal neurons. Acute focal seizures were induced by 4-aminopyridine (4-AP, 15mM, 0.5 l) injection. We utilized the local field potential (LFP) to identify ictal discharge and measure epileptic activity. Photostimulation was performed using a TTL-controlled LED light. Histological studies confirmed the expression of eNpHR3.0 or Jaws in excitatory glutamatergic neurons. Results: The total of 101 seizures was recorded from 9 mice. Following 5-8 weeks of eNpHR3.0 and jaws injections, there was no difference in the duration of seizures between the control and the light stimulation. LFP power, however, decreased from 1895.1 238.1 mV2 to 1317.8107.3 mV2 in eNpHR 3.0 group (p < 0.05, n=4 mice, 50 seizures), and from 2148.3 393.8 mV2 to 1575.5486.3 mV2 in the Jaws group (P < 0.05, n=5 mice, 51 seizures). Conclusions: These results demonstrate that optogenetic silencing of principal network can reduce the seizure activity in neocortex. Furthermore, much work is still needed to improve the strategy of optogenetic therapies for epileptic disorders. Funding: This work was supported by the AES seed grant (T.H.S), the Clinical and Translational Science Center Grant UL1 RR 024996 Pilot Grant (M.Z), the Cornell University Ithaca-WCMC seed grant (M.Z.), and the Daedalus Fund for Innovation (T.H.S & M.Z).