Our lab employs a combination of genetics, molecular, behavioural , and in vivo imaging approaches. We aim to elucidate the molecular, synaptic and circuit basis of social and emotional behaviours in both physiological and pathological conditions.
Research Topic 1: The molecular and circuit mechanisms underlying "romantic love"- pair bonding. A pair bond is the strong affinity that develops in some species between a mating pair, often leading to biparental rearing of offspring and a lifelong bond. About 90% of avian species are monogamous, while less than 5% mammalian species are monogamous including human. Several key neurotransmitters have been implicated to regulate pair bonding, including oxytocin, vasopressin and dopamine. We utilize the BAC clones from a monogamous rodent- prairie vole to make transgenic mice which express the receptors of these key neurotransmitters in a specific way. And these transgenic mice provide us a powerful tool to understand the evolution, formation and maintenance of pair boding behaviours. Drugs targeting on these key neurotransmitters are leading candidates for improving social function of patients with autism and other psychological disorders. This research will shed light on the treatment of social deficits in human.
Research Topic 2: The molecular and circuit mechanisms underlying optimism and pessimism. Human beings show different personality stereotype in their ways of thinking: either more optimistic or more pessimistic. Successful living requires a fine balance between optimism and pessimism. The neural circuit mechanisms underlying optimistic and pessimistic are poorly understood and can only be fully examined in animal models. We successfully established a paradigm to test the optimistic and pessimistic cognition bias in rodents. By applying single cell analysis and in vivo calcium imaging, we are on the way elucidating the key factors mediating the cognition bias. It is notable that individuals who are pessimistically biased have increased risks for many diseases, including depression. Furthermore, optimistic cognitive bias is a significant predictor of physical and mental health. Therefore, this research will provide new insights into the neurobiology of well-being, and guide novel strategies for prevention and therapeutic intervention for diseases.
Research Topic 3: The molecular and circuit mechanisms underlying the emotional symptoms in Alzheimer Disease. Alzheimer’s Disease(AD) is the most common form of dementia and accounts for 60-80% of dementia cases. AD patients suffer from both cognitive symptoms and emotional symptoms. The vast majority of AD research has focused on the neurobiological mechanisms underlying the deficits of learning and memory, whilst the emotional symptoms related to AD onset and progression have been grossly neglected and are poorly understood. We use a new AD mouse model provided by our collaborator to explore the neuronal mechanisms of the emotional symptoms of AD. The potential responsible brain regions and neural circuits will be screened to identify the key signaling pathways and neural circuits. This research will lead to new prevention and treatment strategies against AD.
Research Topic 4: The molecular and circuit mechanisms underlying the encephalopathy of GPI deficiency disease. At least 150 human proteins are attached to membrane by GPI(glycosylphosphatidylinositol) and are called GPI-anchored proteins(GPI-APs). These proteins are very unique since the GPI tails tether them to lipid raft, a highly dynamic microdomain in the membrane. GPI-anchor deficits could cause pronounced neurologic impairments, such as intellectual disability and intractable seizures, cerebral and/or cerebellar atrophy, hypotonia, motor incoordination and ataxia, cortical visual impairment and sensorineural deafness. Our previous work showed that GPI-APs are involved in regulating emotional and social behavior as well. We created multiple mouse models with GPI-AP deficiency. These mouse models mirror the symptoms of human patients and allow us to elucidate the cellular and molecular mechanisms underlying GPI-APs associated disease, and to test the novel therapeutic approaches.