An optogenetic brain implant with EEG monitoring and response for mice

AbstractOptogenetics can be used to selectively stimulate or suppress thering of genetically targeted and spatially targeted mammalian neuronsIt is used to study neuropsychiatric diseases in vivo with mouse models of conditions including epilepsyschizophreniaand Parkinsonandapos sOptogenetics may be used as functional neurosurgical intervention for correcting disease states in the brainIt has been previously shown that seizures have the ability to be halted or reduced by optogenetic activation of inhibitory neurons with the use of ChannelrhodopsinIt has also been shown that expressing HalorhodopsinHRin cortical pyramidal neurons can also reduce seizure propagationBy monitoring EEG data in real timeseizures can be identified at their onset and correcting pulses of optogenetic stimulation may be appliedThis line of research is currently limited by the lack of suitable instrumentsThis project proposes the development of a fully implantablewireless EEG monitor capable of autonomously detecting EEG events in real time and applying correcting pulses of closed loop optogenetic stimulationThe proposed instrument will be compatible with mouse biologythus permitting chronic experiments in the enormous pool of transgenic mouse strains available with photosensitive proteins and validated as models of human diseaseAimwill develop the necessary hardware by combining core technologies demonstrated in existing productsAimwill enable autonomous EEG event detection in the instrumentandapos s micropower logic chip by adapting a computationally efficient algorithm that has been proven capable of classifying EEG events including normal activityseizuresictal spikesinter ictal spikesand polyspikesAimwill test the deviceandapos s ability to detect seizuresapply correcting optogenetic stimulationand reduce the duration of focal seizures induced in mice by the nanoinjection of iron chloridePhase I of this project will make the mouse compatible instrument available for sale to researchers studying circuit theory of the brain and diseases disorders characterized by aberrant EEG states such as epilepsyschizophreniaAlzheimerandapos sand obsessive compulsive disorderPotential follow on Phase II would develop the technology into a medical instrument that aborts focal seizures in humans who suffer from pharmaceutical resistant partial epilepsyapproximatelymillion peopleA wireless instrument capable of simultaneous EEG recording and optogenetic stimulation in mice will enable a new class of experiments of epilepsyschizophreniaAlzheimerandapos sobsessive compulsive disorderand other conditions characterized by aberrant electrophysiologyIn addition to aiding basic research and the identi cation of pharmacological treatmentsthe instrument will enable a new class of functional neurosurgical interventionThe instrument will demonstrate a new treatment of focal seizures in patients suffering from pharmaceuticalresistant partial epilepsy