Optogenetic Approaches for Controlling Seizure Activity

Abstract

Optogenetics, a technique that utilizes light-sensitive ion channels or pumps to activate or inhibit neurons, has allowed scientists unprecedented precision and control for manipulating neuronal activity. With the clinical need to develop more precise and effective therapies for patients with drug-resistant epilepsy, these tools have recently been explored as a novel treatment for halting seizure activity in various animal models. In this review, we provide a detailed and current summary of these optogenetic approaches and provide a perspective on their future clinical application as a potential neuromodulatory therapy.

Keywords: Epilepsy; Neuromodulation; Optogenetics.

Figure 1. Optogenetic vs. electrical stimulation approaches to neuromodulation

(A) The effects of electrical stimulation is highly dependent on stimulation parameters and acts nonspecifically on cells around the stimulating electrode. The effects of optogenetic excitation (B) or inhibition (C) can be cell-type specific. Figure reprinted from Nature Methods 8, 26–29 (2011).

Figure 2. Anatomical and cell-type specific approaches to inhibit seizure activity

The various optogenetic approaches utilized to halt seizure activity can be grouped by structure (a) or cell types (b).

Figure 3. Closed-loop vs. open-loop approaches to light delivery

Optogenetics can be utilized to target specific cell types in the epileptic network at the seizure focus, remote modulators of the seizure focus, or downstream propagators of seizure activity. Light can either be delivered manually in an open-loop fashion, or automatically in response to a detected seizure (closed-loop).

Figure 4. Translational challenges for optogenetics

Several challenges with gene expression and light delivery need to be addressed to facilitate effective translation of optogenetic techniques into a clinical setting. Some potential solutions to these challenges are listed. Abbreviations: CED: convection-enhanced delivery; CSF: cerebrospinal fluid.