Memory is critical for survival. Its alteration appears in many neurological disorders such as Alzheimer’s disease (AD), dementia, posttraumatic stress disorder, and traumatic brain injury. Our long-term goal is to understand synaptic molecular dynamics underlying memory formation in health and its impairments in AD and related dementias.
We address the following questions using multifaceted approaches: biochemistry, immunohistochemistry, live cell imaging, adeno-associated virus (AAV) production, AAV-mediated gene delivery, cell-type-specific and multi-color fluorescent protein labeling, tissue clearing, and behavioral tests.
Q. How do neurons encode learning and memory?
Long-term potentiation (LTP) has been considered a cellular mechanism for learning and memory. Many key molecular players for LTP induction have been identified (including NMDA receptors, CaMKIIα, AMPA receptors, and membrane-associated guanylate kinase [MAGUK] family). However, many questions remain at cellular and molecular levels—for example, the maintenance of LTP, etc.
Q. How does AD result in synaptic dysfunction?
AD is a progressive and degenerative brain disease. Brains from AD patients are known to accompany the presence of increased protein accumulations such as intracellular tau inclusions (neurofibrillary tangles) and extracellular β-amyloid (Aβ) deposits (senile plaques). The tau and Aβ pathologies have been studied extensively as the cause of AD pathogenesis and are supported by many AD model mice with familial AD mutations. While AD treatment strategies have focused mainly on these pathologies, synaptic dysfunction in early AD has received much less attention even though synapses are the fundamental units that mediate neuronal plasticity and memory.
Q. What do neurons require at synapses to have memory ability improved in health and AD?
Despite the tremendous efforts for the past decades, little is known to facilitate healthy memory or reverse deficits in memory disorders. We focus on novel molecular and pharmaceutical approaches to improve memory ability in heath and AD models.