Automatic Focal Seizure Suppression System: An Application of Optogenetic Gene Silencing
We propose a new intelligent method of focal epileptic seizure suppression using synthetic biological circuits for the purpose of activating optogenetic tools precisely at the locus of the seizure. It can be expected that decreasing the hyper-activation of neurons or disturbing the pattern of seizure in its onset with high spatial-resolution can be useful in controlling the seizure. Our general idea is the following: If the promoter of any up-regulated gene in epileptic neurons is recognized, the appropriate vector can be designed for targeting the involved neurons. Then we can target the transport of NpHR to epileptic neurons so that the hyper-activated epileptic neurons can be suppressed before and after the onset of seizure; hence, it will be possible to control the seizure by use of yellow light. We have designed a three-step regulatory network:
1. | Targeting and gene expression mechanism: We designed a network consisting of two vectors: the temporary vector (T) and the permanent vector (P). The T vector has the induced-promoter, and, at the onset of the seizure, it is expressed. In this vector, there is a separate promoter for fluorescent protein (X-promoter for XFP). The X-promoter is repressed by the induced-repressor in the P vector. The second part of the P vector has a down-regulated section, and its activation is based on the expression of activator protein. The P vector has an autofeedback or memory loop in it so it can be expressed permanently when the activator concentration is above a threshold. Our idea differs from previous studies in having a genetic driver circuit that detects the involved neurons in epilepsy and builds a permanent memory of NpHR gene expression. | ||||
2. | Tracking epileptic neurons: it is now possible to find the local position of targeted epileptic neurons by processing the data of EEG or by other imaging systems, such as fMRI.4,5 Using our proposed method, it is possible to track the exact position of epileptic neurons by watching the fluorescent XFP proteins. | ||||
3. | Optogenetic automatic system of seizure suppression: An automatic seizure-suppression system may be designed, assuming that the focal area of our interest is small and accessible.6 We would hope that this method might disturb the synchronization of epileptic neurons and decrease the hyperactivity of epileptic neurons. Our hypothesis needs to be implemented in animal studies in order to be validated. If so, it will be possible to control the involved neurons in the epileptic attack by yellow light interaction. |
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