Research

Synapse formation and elimination are fundamental elements in the initial construction of neural circuits, the experience-dependent modification of the nervous system, and ultimately cognitive behavior. Neuronal activity drives the modification of neural circuits by strengthening and weakening the connectivity between neurons. Mikyoung Park’s laboratory is interested in how synaptic functions are regulated at the cellular and molecular levels in the context of synaptic plasticity, spatial learning, and cognitive flexibility in health and diseases.

1. Synapse and synaptic plasticity

Synapses are fundamental units of brain function and possess the remarkable ability to change their strength in function and structure through synaptic plasticity. Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that has long been considered a synaptic correlate for learning and memory. A type of glutamate receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor (AMPAR), has been investigated intensively as a key player in synaptic modifications involved in synaptic transmission, synaptic plasticity (Park et al., 2004; Park et al., 2006; Cho, Kim et al., 2015; Park, 2018; Woo, Hur et al., 2020; Hwang, Hur et al., 2021) and ultimately learning and memory. LTP and long-term depression (LTD), another well-characterized form of synaptic plasticity in the hippocampus, are expressed by long lasting changes of AMPAR-mediated synaptic responses. Exocytosis and endocytosis of AMPARs play critical roles in LTP and LTD, respectively, in aspects of both functional and structural plasticity of synapses. We are interested in imaging the cellular and molecular mechanisms underlying synaptic function and synaptic plasticity.

2. Spatial learning and cognitive flexibility

Spatial learning is the process of recording the information required to navigate a location, and cognitive flexibility (also often called behavioral or memory flexibility) is the process of learning a new location that involves two courses, forming a new memory and suppressing the previous memory. Synaptic plasticity, including LTP and LTD, is generally considered as the cellular basis of learning and memory in the brain. Specifically, a myriad of preceding studies have reported the functional significance of LTP in mediating learning and memory with extensive molecular mechanisms. In addition, many studies have demonstrated that LTD is required for memory flexibility. We are interested in how cognitive flexibility, involving both memorizing and forgetting processes, is mechanistically interconnected through the precise tuning of the degrees of LTP and LTD.

3. Neurogenerative diseases and neuropsychiatric disorders

The maintenance of LTP, LTD, and memory strength within adequate physiological ranges is essential for the proper functioning of the brain in various cognitive and behavioral contexts. Neuronal dysfunctions that are associated with LTP and spatial learning and lead to cognitive decline and progressive memory loss, are the characteristics of the most common neurodegenerative disease, Alzheimer’s disease. Excessive memory strengthening and/or impaired forgetting processes likely contribute to a deficit in memory flexibility, which may lead to the establishment of pathological conditions, such as post-traumatic stress disorder, autism spectrum disorder, and schizophrenia. We explore the pathophysiological mechanisms underlying Alzheimer’s disease and autism spectrum disorder.