We are interested in the cellular and molecular mechanisms underlying axon guidance, synapse formation and activity-dependent refinement of neural circuits.
Transduction Mechanisms underlying axon guidance. Using cultured Xenopus spinal neurons and cerebellar granule cells, we are examining the cytoplasmic events associated with neurite growth and the response of the growth cone to extracellular guidance cues. By applying defined extracellular gradients of guidance cues that cause attractive or repulsive turning of the growth cone, we can examine the early cellular responses at the growth cone triggered by the guidance cue and the involvement of various cytoplasmic signaling pathways in mediating the turning response. For long-range axon guidance based on the detection of chemical gradients, the growth cone must be able to respond reliably to small gradients of guidance cues across its surface. This may be achieved by amplification of guidance signals through intracellular transduction mechanisms. In addition, as the growth cone migrates in an environment in which the basal concentration of the guidance cue varies by many orders of magnitude, it also needs to constantly re-adjust its sensitivity through a process called adaptation. Current efforts are aimed at understanding the molecular mechanisms underlying the amplification and adaptation of guidance signals at the growth cone.
Activity-induced modifications of neural circuits. Early synaptic connections in the developing nervous system undergo substantial remodeling in response to electrical activity. Using nerve-muscle cultures, hippocampal slices, and retinotectal system in vivo, we are examining how various patterns of electrical activity and sensory inputs induce the strengthening or weakening of synaptic connections, as well as the up- and down-regulation of the intrinsic excitability of pre- and postsynaptic neurons. We are also interested in understanding how such activity-induced synaptic and neuronal modifications influence the developmental refinement of specific neuronal connections, using the Xenopus retinotectal system as a model system. In studying synaptic plasticity in nerve-muscle and hippocampal cultures, we have discovered an extensive spread of long-term depression (LTD) and long-term potentiation (LTP) from the site of induction to other synaptic sites within the neural network. This spread (or "propagation") of synaptic modifications is highly specific, implying selective spatial distribution of activity-induced changes within the network. We are currently studying whether various forms of LTP/LTD propagation occur in brain slices and in vivo. In the long run, we hope to understand the cellular signaling mechanisms underlying the propagation of LTP/LTD and the implication of such propagation for the processing and storage of information in the nervous system.
Neurotrophins as synaptic modulators. Based on the observation that many exogenous neurotrophic factors can exert acute effects on neuronal morphology and synaptic efficacy, we are examining the possibility that synaptic secretion of neurotrophins are involved in the activity-dependent modification of synaptic connections. Specifically, we are studying how secretion and cellular actions of neurotrophins at developing synapses are regulated by the electrical activity. We are also interested in understanding how long-range cytoplasmic signaling in neurons can be achieved by localized reception of neurotrophins at the synapse.
Dr. Poo is interested in how neural stem cells differentiate into different neuronal types, in response to specific cellular environment within the neural tissue, and the factors that influence the incorporation of differentiated neurons into existing neural circuits within the neural tissue and the input/output functions of incorporated neurons. To address these issues, they need to develop a variety of cell culture, brain slice culture, and acute brain slice model systems, and use a combination of molecular, cellular and physiological experimental approaches to analyze neuronal differentiation, the formation and functions of neuronal connections.
In the News
Neuroscientist Mu-ming Poo “leads a double life,” according to a piece in the journal Nature. He spends three-quarters of his time doing research on campus, but for the past decade has spent one day a week nurturing budding neuroscientists at the Institute of Neurosciences in Shanghai.