Our work concentrates on the glutamatergic neurotransmitter systems in hippocampus and olfactory bulb. The long range goal of our lab is to understand how external inputs (such as electrical stimulation for brain slice and sensory experience for olfactory bulb) take their role in shaping the synaptic connection in early development.
Glutamatergic receptor lateral movement and synaptic plasticity. Glutamatergic receptor trafficking through endocytosis and exocytosis is well determined by previous studies while lateral movement between synaptic and extrasynaptic domain in postsynaptic membrane plane was first observed in 2002. Few studies have been conducted since then to uncover the implication of this new trafficking route on synaptic plasticity, especially the polarity or developmental change of it. By using whole-cell patch clamp recording our lab will try to study how and to what extent lateral diffusion of NMDA and AMPA receptors could change the induction of LTP or LTD and how this change is affected by early development. Since opposing role of synaptic and extrasynaptic glutamatergic receptor was determined by previous study (i.e. Calcium flux through NMDA receptors located in the synapse initiates changes in synaptic efficacy and promotes pro-survival events, whereas calcium flux through extrasynaptic NMDA receptors is coupled to cell death pathways), our work on elucidating the role of glutamatergic receptor will in the long run benefit the clinical treatment of some neurodegeneration disease.
Activity-dependent synaptic plasticity in early development of olfactory system. The brain is a massive network of electrically active neurons that communicate with each other through synapses. Throughout our life, the brain responds to experience by adjusting the strength of coupling of synapses and by changing the spatial pattern of connections between neurons. In early developmental stage, activity- or sensory-dependent synaptic plasticity is well documented in sensory systems other than olfactory system. We seek to understand if and how synapses in the olfactory bulb are modified by experience. Using perforated whole-cell patch clamping recording along with simultaneous calcium imaging on mitral cell, we will study how olfaction experience shapes the maturation of glutamatergic neurotransmission. This work will help to elucidate how cells in lower olfactory central system respond and adjust to odor environment change (for example, does olfactory system also have so-called ¡°critical period¡± comparable to that in visual system?). We will use intact larval zebrafish as our animal model so as to conduct experiments in vivo.
Role of glutamate transporter in persistent pathological pain condition. Glutamate is a neurotransmitter critical for spinal excitatory synaptic transmission and for generation and maintenance of spinal states of pain hypersensitivity via activation of glutamate receptors. Understanding the regulation of synaptically and non-synaptically released glutamate associated with pathological pain is important in exploring novel molecular mechanisms and developing therapeutic strategies of pathological pain. The glutamate transporter system is the primary mechanism for the inactivation of synaptically released glutamate and the maintenance of glutamate homeostasis. We aim to determine the role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states through collaboration with Dr. Tao Yuan-Xiang¡¯s lab at John Hopkins University Medical School. Dr. Tao¡¯s laboratory found that, in pathological pain states, inhibition of glutamate transporter activity produced antinociceptive effects, which is opposite to pro-nociceptive effects under normal conditions. The underlying mechanism is unclear. We hypothesize that pathological persistent pain may cause cellular energy insufficiency that inverses the glutamate transporter operation to release glutamate in the spinal cord. Blocking the reversed glutamate transporter-mediated glutamate release may be an underlying mechanism of antinociception produced by glutamate transporter inhibition under chronic pain conditions. We believe that this study will present innovative concepts regarding glutamate transporter functions under persistent pain conditions and provide new insights into the molecular mechanism of persistent pain. It might also lead to novel therapies for clinical persistent pain.
Director:Wei Lu(M.D.,PhD,Professor and supervisor of doctoral candidates)
Office Tel:0086-25-86862822
