In the brain, dendrites of pyramidal neurons contain intermingled excitatory and inhibitory synapses. Synaptic connections dynamically change during development and throughout our lifetime, yet the brain can properly maintain an optimal ratio of synaptic excitation to inhibition. Failure to establish such a delicate balance has been implicated in psychiatric and neurodevelopmental disorders including autism, schizophrenia, and substance abuse.
To study the spatiotemporal mechanisms that govern activity-dependent excitatory and inhibitory synaptic and circuit plasticity, we combine two-photon imaging and two-color, two-photon uncaging with electrophysiological measurements to examine the functional implications for synapse, neuron, and circuit development. We also use calcium imaging, optogenetics, and chemogenetics in conjunction with two-photon microscopy to monitor and manipulate neuronal activities.
With this combination of approaches, we are beginning to dissect (1) how the integrative properties of single excitatory and inhibitory synapses and neurons support the early neural circuit formation and (2) whether early dysregulation of synaptic signaling gives rise to the pathogenesis of neurodevelopmental disorders. Our long-term goal is to determine the functional impact of the neurotransmitters and neuromodulators (e.g. glutamate, GABA, dopamine, serotonin) on cortical circuits during development, plasticity, and in disease.
On-going projects:
Serotonergic modulation of excitatory and inhibitory synaptic plasticity during prefrontal cortex (PFC) development.
Role of inhibitory synapses in shaping excitatory synapses & circuits during brain development.
Serotonin dysfunction in the PFC of Dp16 mouse model of Down Syndrome.
The effects of psychedelics (e.g. psilocybin) on brain development and neuroplasticity.
The effects of perinatal cannabidiol (CBD) exposure on PFC development.
Dissecting neural circuits underlying early life stress-induced PFC dysfunction.
Physiological and pathological role of amyloid precursor protein (APP) in neural circuit development.