 So one out of every five people has experienced depression at some point in his or her life. So according to the World Health Organization, the prevalence of depression is surging over the years. And by 2017, it has surpassed heart disease and cancer and become the number one disabling disease in the world. So regarding the cause of depression, an old famous hypothesis points to a lack of monoamines in the brain. So monoamines include dopamine and serotonin, which are chemical messages associated with pleasure. However, one major problem of this hypothesis is that although classical antidepressants can boost monoamine levels within hours, but the improvement of mood is much delayed, often taking weeks to months. However, the situation may be changing with the emergence of this miracle drug called ketamine, which is hitting a lot of headlines. So in just a conscious to the classical antidepressants, ketamine causes a very rapid antidepressant response and in a large fraction of treatment-resistant patients. And the effect can kick on as early as one hour. So for this reason, ketamine has been argued to be the most significant discovery in the mental health field because it may help review the core mechanism of this detrimental disease. So we all know that ketamine is a blocker of a major receptor molecule in the brain called NMD receptor. But this receptor molecule is everywhere in the brain. So then the million-dollar question is, what exactly is the target of ketamine? Which brain region and which cell group? So a recent work from my lab showed that a brain area called the lateral-habanular LHB may be a crucial mediator of ketamine's effects. So although it is a tiny area, the LHB plays a powerful role in regulating negative emotions such as stress and disappointment. For example, when monkeys don't get expected orange juice or when people don't get expected celery rays, their LHB neurons will fire like crazy and will go on to inhibit the dopamine neurons in the reward center. So consistently, brain imaging shows that in depressed patients as well as in depressed animal models, habanular becomes hyperactive as if too much negativity is going on in the brain. So in my lab, we use mice and rats to study depression and we stumbled upon ketamine serendipitously when we locally infused the drug just into this area. We found a dramatic antidepressant response. So in order to model depressive-like behaviors in animals, we use these two different assays. One is called the false swim test, which will put animals into water and see how quickly they give up swimming and become immobile. So that models behavioral despair. And the other sucrose preference tests for anhedonia, which is an inability to feel pleasure. So we found that within one hour after infusion into the lateral habanular, ketamine can significantly reduce the immobility in the swim test and increase the preference for the sucrose water over regular water. So what does ketamine do to the LHB neurons? With electrophysiology recording, we found LHB neuron has a special pattern of activity called burst firing. So under this pattern, neuron will fire very rapidly within a short interval. So compared with this tonic single spike, burst firing will convey information more efficiently, sort of like a machine gun versus a rifle. So we found in depressed animal, the percentage of burst neuron is greatly enhanced and ketamine can effectively eliminate this burst firing. So we can use light to stimulate burst-like activity in these neurons by expressing light-sensitive ion-channel molecules in this region, sort of like installing a light switch there. So now in these animals, when we drive burst firing with light, animal go directly into this immobile sort of despair-like state. However, if we inject animal with ketamine first, then they will keep trying and swimming because ketamine blocks this light-induced burst firing. Likewise, ketamine also blocks an hedonia induced by this light-stimulated burst. So to wrap up in this model, we think that under depressed state, neurons in the anti-reward center LHB will send a stronger suppression onto the downstream reward center through the burst firing. So by blocking the receptor molecule that is required for burst, ketamine can then silence the burst and relieve this suppression break onto the reward center to combat depression. So we know that ketamine may have some side effects such as dissociative effects, addiction or bladder problems. So we hope that by understanding how ketamine works, we may be able to design the new generation treatment for depression, but without the same side effects. Thank you very much.