Non-Coding RNA-Mediated Control Of Neuronal Excitability And Epilepsy.

Human and animal behavior depends on the tight balance between excitatory and inhibitory signals that arise within neurons in the brain. Epilepsy occurs when the excitatory signals take over, either due to aberrant activity of excitatory neurons or malfunction of inhibitory neurons. Our proposal aims to curb excessive excitatory signals during epilepsy. We found that a single brain-expressed small RNA, which represents a family of the so-called microRNAs, is capable of controlling neuronal excitability. Our experiments revealed the ability of the microRNA miR-128 to govern motor behavior and to prevent seizures induced by various factors. The advantage of microRNAs is that they can be formulated relatively easily into a therapy. Both microRNAs as well as microRNA antagonists can potentially be used to modulate the activity of neurons. Our aim is to use miR-128 or its antagonists to suppress pathological neuron excitation causing fatal epilepsy in mice, and to extend our findings to further advance human epilepsy treatment.