A major challenge in modern neuroscience is to understand how various brain functions emerge from the underlying specific neural circuits. Among the cellular constituents in many brain circuits, diverse types of inhibitory interneurons that release neurotransmitter γ-aminobutyric acid (GABA) generate the rich and fine inhibitions. Functional deficiencies in specific sub-population of interneurons are known to directly be associated with certain neuropsychiatric diseases. The long-term objective of my lab research is to study the interaction mechanisms between inhibitory synaptic circuits and early behavioral experiences under both normal physiological and neuropsychiatric conditions. Specifically the following lines of experimental research have been carried out in the lab.
The integration of inhibitory and excitatory synaptic inputs is critical in determining the dynamic of spike output and functional property of principle (pyramidal) cells. Recently, we have derived a simple empirical arithmetic rule describing the non-linear integration of concurrent dendritic excitatory and inhibitory inputs in a pyramidal cell (PNAS, 2009) and further generalized a bilinear rule that nicely approximates the dendritic integration of multiple spatiotemporal inputs in a single-compartment (point) neuron model (PLoS One, 2013; PLoS Compt Biol, 2014). The latter generalized rule could offers an excellent tool for more realistic modeling of neuronal dynamics associated with brain functions in a large scale network model. Providing the existence of diverse subtypes of GABA interneuron, we aim to provide a quantitatively and comprehensive view on how the domain-specific integration of excitatory and inhibitory inputs determine the neuronal processing functions and activity dynamics, with experimental and modeling approaches.
Postnatal critical period (CP) is a defined time window during which the brain connectivity is most malleable to sensory experience. It is best exemplified by the critical-period ocular dominance (OD) plasticity of developing primary visual cortex (V1) in mammals, which is gated by developmental maturation of cortical GABA inhibition. Despite of extensive studies on the molecular and cellular mechanisms for the CP plasticity, the neural activity induction and circuitry mechanisms, especially those involved with inhibitory circuits, remain elusive. Our recent work suggests the GABA inhibiton-dependent emergence of CP-featured coincident synaptic inputs from the two eyes to the V1 that mediates the visual input-dependent OD plasticity (J Neurosci, 2014), and critical role of proper inhibitory parvalbumin (PV)-expressing synaptic circuit in gating the CP(Nat Commun, 2014). The ongoing studies focus on (1) searching for CP landmark activity and its inhibitory circuitry mechanisms; and (2) probing physiological traces of the CP plasticity in local inhibitory circuits, with in vivo recording, optogenetics and TRAP approaches.
Proper neuronal wiring in local circuits requires normal sensory experiences during the CP. Along this line, we aim to use the optogenetics-assisted synaptic mapping methods to dissect principles of cortical wiring across different cortical functional area and to demonstrate the existence of plasticity of cortical wiring induced by early experience during the CP. Most neurodevelopmental diseases, e.g., autism and schizophrenia, are known as diseases of synapses. We are extremely interested in mapping out the abnormal cortical wiring and its maladaptive plasticity in mouse models of these diseases.