Опыт применения оптогенетических подходов к исследованию функций мозга и протезированию дегенеративной сетчатки

Abstract

Optogenetics, which allows control the activity of neurons by means of light after expression of light-activated proteins in them, is a powerful tool in neuroscience that determined significant progress in the study of brain functions in the last decade. The progress of optogenetics crucially depends on the development of new molecular tools - light-activated proteins. In 2015, the natural light-activated chlorine channel GtACR2 was identified. This channel is capable of suppressing neuron activity with high efficiency in optogenetic experiments. We discovered the unique properties of this channel, showing that in GtACR2-expressing neurons, the light stimulus, in addition to strong inhibition, can also induce the generation of action potentials, which occurs, apparently, in axon terminals of the neuron due to the altered chlorine reversal potential in these cell compartments . In our work, we use optogenetic methods to study the cellular mechanisms of learning and memory. Using the expression of channelrhodopsin2 in the network of presynaptic neurons, we used light stimulation to study the properties of synaptic connections and their plasticity in a whole population of neurons in a single experiment. One of the promising areas of clinical application of optogenetics is its use for prosthetic of degenerative retina. A variant of this approach is to recreate the ON / OFF receptive field of ganglion neurons by targeted expression of the excitatory light-activated protein in the central part of the ganglion cell, and the inhibitory opsins in the peripheral. In the framework of this approach, we created a bicistronic construct that carries the genes of the excitatory and inhibitory opsins, the expression of which was able to lead to the restoration of ON / OFF interactions typical for ganglion cells.