SCN8A encodes a major voltage-gated sodium channel expressed in CNS and PNS neurons.  Gain-of-function and loss-of-function mutations contribute to  human disorders, most notably Developmental and Epileptic Encephalophy (DEE). More than 600 affected individuals have been reported, with the most common  mechanism of de novo, gain-of-function mutations.  We have developed constitutive  and conditional models of gain- and loss- of function mutations in the mouse and  characterized the effects of on neuronal firing and neurological phenotypes.  Using CRE lines with cellular and developmental specificity, we have probed the effects of activating  mutant alleles in various classes of neurons in the developing and adult mouse.   Most recently, we are testing genetic therapies that reduce the expression  of gain-of-function mutant alleles.  We are comparing the effectiveness of allele specific  oligos (ASOs), viral delivery of shRNAs, and allele-specific targeting of mutant alleles  using Crispr/Cas9 in mouse models of DEE.

Controlling biological processes using light has increased the accuracy and speed with which researchers can manipulate many biological processes. Optical control allows for an unprecedented ability to dissect function and holds the potential for enabling novel genetic therapies. However, optogenetic experiments require adequate light sources with spatial, temporal, or intensity control, often a bottleneck for researchers. Here we detail how to build a low-cost and versatile LED illumination system that is easily customizable for different available optogenetic tools. This system is configurable for manual or computer control with adjustable LED intensity. We provide an illustrated step-by-step guide for building the circuit, making it computer-controlled, and constructing the LEDs. To facilitate the assembly of this device, we also discuss some basic soldering techniques and explain the circuitry used to control the LEDs. Using our open-source user interface, users can automate precise timing and pulsing of light on a personal computer (PC) or an inexpensive tablet. This automation makes the system useful for experiments that use LEDs to control genes, signaling pathways, and other cellular activities that span large time scales. For this protocol, no prior expertise in electronics is required to build all the parts needed or to use the illumination system to perform optogenetic experiments.