 Today I want to start my talk with one fact and one question. The fact is that there are 4.5% adults with cognitive disability and this rate can go up to 9% for the older people. So my question is, is there anything we can do to help by improving the learning ability? From a clinical view, the impaired learning is a common symptom for many brain disorders such as Alzheimer's disease and autism. As a neurobiologist, I start to wonder whether there is any shared mechanism underlying such a common but serious symptom. Thanks to large genetic data, we have known a lot of risk genes related to these brain disorders. Very interestingly, most disease genes encode proteins either at the synapse where neurons receive the information or in the nucleus where DNA gets produced. Since many brain disorders share similar risk genes and also show the impaired learning, is it possible that dysregulated communications between the synapse and the nucleus need to be impaired learning as a common symptom for such disease? Indeed, our experience does have the ability to shape our DNA in the brain. We even know the molecular pathways which are initiated at synapse where kerosene signal influx and then the signals are propagated to the nucleus through sharpening protein to regulate nuclear gene transcription. It's not another idea to manipulate signaling pathways to improve learning ability. Back to 20 years ago, scientists have made smarter minds by increasing synaptic functions which learn faster, remember longer, and the soul makes it better. After that, more and more genetic minds have been made to improve learning ability. However, everything suggests such improvements come at a cost that cannot be easily underestimated. For example, such minds have a higher risk for cancers, seizures, and chronic pain. All such side effects are not surprising because both synaptic activities or nuclear gene transcription have other important synaptic functions. So can we specifically manipulate the sharpening protein which are the dynamic connections between the brain activities and the gene transcription? We applied this strategy to gamma-chemical 2, a protein transnogating into the nucleus upon neural activations. Gamma-chemical as a molecule for the memory has a big capacity for signal transcription because it contains 12 subunits and can be regulated by the neural activity. More importantly, genetic data suggests gamma-chemical 2 is a risk gene for international disability which often shows no IQ and the impaired learning. So is it possible that the mutation following such human patients impairs the sharpening function which in turn affects the learning? To address this question, we used mice as a model because they share similar learning principles like neuroplasticity as humans. After deleting the genes, encoding the sharpening protein, both the mice and the neurons look normal, minimizing the concern for the development. We examined the mice using water mates which is a classic memory test by putting the hidden platform under the water and train the mice to find it. Observing the mice without the sharpening protein spent much longer time to find out the platform, suggesting the impaired learning consistent with the idea of the disabled communications between the brain activities and the nuclear DNA productions. Indeed, the neurons also notice the ability to send the nuclear signal denoted by the red color here into the nucleus to regulate gene transcription or gene expression. Finally, we inserted the human version of the sharpening protein into the brain. Importantly, you can see that inserting the sharpening protein but not the mutation found in the human patients fully rescued the learning defects. Taking together, we think that the impaired learning in many brain disorders may be caused by a network encoded by disease genes. We rescued this by inserting the sharpening protein indicating the chance for improving human learning ability in the future. Thank you.