NeuroLSD1: Splicing-Generated Epigenetic Enhancer of Neuroplasticity

The acquisition and maintenance of the specific neuronal functions underlying learning, memory, and emotion require transduction of environmental stimuli into remodeling of neuronal circuitry. This process occurs via induction of plasticity-related transcriptional programs. The epigenetic enzyme lysine-specific demethylase-1 (LSD1), also known as lysine demethylase 1A (KDM1A), and its neurospecific splicing variant neuroLSD1 have been implicated in this process through an antagonistic mechanism. Specifically, LSD1/neuroLSD1 are involved in the negative and positive regulation of activity-evoked transcription of immediate early genes (IEGs) impacting memory formation and emotional behavior. Remarkably, the splicing process generating neuroLSD1 is homeostatically modulated by environmental contingencies, further implicating the LSD1/neuroLSD1 dual system as a modifier of information processing in the brain.