Synapses are sites that connect neurons each other to extend networks in the human brains and transmit signals required for cognition and thought in daily activities. We intend to uncover mechanisms by which brains function, by studying molecules act at synapses. We also aim to uncover the pathophysiology of neuropsychiatric disorders caused by dysfunctions of these molecules.
Synapses are highly specialized asymmetric intercellular junctions that transduce chemical signals into the electrical responses that operate communications throughout the nervous system, including the processes underlying perception and thought in the human brain. The orchestration of thousands of molecules localized to pre- and postsynaptic terminals regulates the formation, activation and degeneration of synapses. Hence, the impairment of a portion of these molecules disturbs the coordination of this machinery and results in an aberrant mental condition. A growing body of evidence suggests that synapses play a pivotal role in the pathogenic processes of neurological disorders. Nevertheless, the molecular mechanisms behind such disruptions remain elusive.
We intend to uncover molecular mechanisms affecting synapse in neuropsychiatric disorders. We primarily focus on the synaptic cell adhesion molecules called gNeurexins and Neuroliginsh which have been causally implicated in psychiatric disorders including autism, schizophrenia and drug addiction. To this end, we utilize lines of mutant mice that we have generated by gene targeting, and analyze their synaptic functions by multidisciplinary approaches including biochemistry, morphology and electrophysiology. We also study their behavior and assess the relevance between the molecular function and human disorders.
Besides this, we are studying the Á-secretase function in neurodegeneration. We found that the mice lacking Nicastrin, an essential component of Á-secretase, in the brain showed neurodegeneration. We are searching the mechanism by which Nicastrin deficiency causes neurodegeneration.
3-1-1 Asahi, Matsumoto,