An extraordinary feature of brain is its capacity to amend neuronal connectivity in response to ongoing experience or learning. Despite tremendous advances in our understanding of the plastic nature of neurons, how activity generated by sensory experience modifies neuronal wiring and ultimately alters an animal’s behavior are still poorly understood. Our long-term goal is to decipher how the architecture of neuronal connectivity in a mammalian brain is properly constructed and revised by constantly changing environmental inputs during early brain development. This will be accomplished using a combination of genetic, electrophysiology, and imaging approaches to deliver highly-specific manipulations to selected neurons in vivo and subsequently determine the functional consequences for synapse, neuron, and circuit development.
- Mechanisms governing wiring of individual cortical neurons.
It is conceivable that very specialized mechanisms such as localization, maintenance, and removal of synaptic molecules underlie synapse formation and maturation, and such mechanisms are crucial for the initial establishment of synapse specialization. In this project, we will determine how synaptic molecules are dynamically distributed and rearranged during synapse formation, and how these protein dynamics influence the establishment of synapses and circuits.
- Mechanisms of inhibitory circuit formation.
Dendritic spine dynamics such as formation, maturation, and pruning, and modulation of receptors or channels at single excitatory synapses have been extensively studied for the last decade. However, we unfortunately have not acquired much knowledge about the detail cellular and molecular mechanisms at individual inhibitory synapses. This limitation has hampered to draw a complete picture of neuronal connectivity in a neuron. In this project, we will focus on inhibitory synapse development and plasticity at the level of single synapse.
- Synapse and circuit disruption in neurodevelopmental disorders.
The goal of this project is to investigate whether there are fundamental abnormalities in neuronal connectivity and function in mouse models of human neurodevelopmental disorders such as mental retardation, epilepsy, and autism spectrum disorders. In recent years many disease-associated mutations have been identified, yet the functional importance of the targeting genes is still largely unknown. Understanding how a specific gene mutation leads to disease will require a functional examining of the perturbations to synapse, cell, and circuit function that it causes.