Mu-Ming Poo
Professor (Molecular & Cell Biology)
Email: mpoo@berkeley.edu
Research areas: Cellular and Molecular Neuroscience, Developmental Neuroscience, Systems and Computational Neuroscience
We are interested in understanding the cellular and molecular mechanisms underlying the guidance of nerve growth, the formation and plasticity of synapses, and activity-dependent modification of neural circuits.
Transduction mechanisms in 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 axonal growth cone to extracellular guidance factors. By applying defined extracellular gradients of guidance factors that cause attractive or repulsive turning of the growth cone, we are examining early cellular responses at the growth cone triggered by the guidance factor and the involvement of various cytoplasmic signaling pathways in mediating the turning response. Of particular interest is the elevation of calcium ions in the growth cone, which appears to serve as an early signal for both attractive and repulsive growth cone responses induced by many extracellular guidance factors. For long-range axon guidance based on the detection of extracellular gradients, the growth cone must respond reliably to small gradients of guidance factors 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 (adapt) its sensitivity to the guidance factor. Our current efforts are aimed at elucidating the mechanisms underlying the amplification and adaptation of guidance signals within the growth cone cytoplasm.
Activity-induced modification of neural circuits. Early synaptic connections in the developing nervous system undergo substantial remodeling in response to electrical activity. Using nerve-muscle cultures, acute and cultured 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 intrinsic excitability of pre- and postsynaptic neurons. Using the Xenopus retinotectal system as a model system, we are interested in understanding how such activity-induced synaptic and neuronal modifications may participate in the developmental refinement of neural circuits and the emergence of integrative function of neural circuits, as reflected by specific receptive field properties of the neuron, e.g., directional selectivity.
Spike-timing dependent plasticity. Information in the nervous system may be carried by both the rate and timing of neuronal spikes. Recent findings of spike timing-dependent plasticity (STDP) at many excitatory synapses have fueled the interest on the potential role of spike timing in the processing and storage of information in neural circuits. Induction of long-term potentiation (LTP) and long-term depression (LTD) in a variety of in vitro and in vivo systems was found to depend on the temporal order of pre- and postsynaptic spiking. We have also shown spike-timing dependent bi-directional modifications of neuronal excitability and dendritic integration in cell cultures and brain slices. We are currently examining the potential functions of STDP at the synaptic and cellular levels in activity-dependent processing and storage of information in neural circuits of the hippocampus, visual cortex, and ventral tegmental area of the midbrain.
Spread of LTP/LTD in nerual circuits. In studying synaptic plasticity in nerve-muscle and hippocampal cultures, we discovered an extensive spread of LTP and LTD 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 function of such propagation for the distributed information processing and storage in neural circuits.
Neurotrophins as synaptic modulators. Based on the observations that 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 the secretion and cellular action of neurotrophins at developing synapses are regulated by electrical activity. We are also interested in understanding how long-range cytoplasmic signaling in neurons can be achieved by localized transfer or reception of neurotrophins at the synapse. Finally, we are also examining the action of BDNF in sensitizing the reward circuit towards activity-dependent modulation associated with cocaine addiction.
Selected Publications
Zhou, Q., Tao, H., and Poo, M-m. 2003. Reversal and stabilization of synaptic modifications in a developing visual system Science 300: 1953-7.
Du, J-l. & Poo, M-m. 2004. Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system Nature 429: 878-83.
Wang, G.X., and Poo, M-m. 2005. Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones Nature 454: 898-904.
Liu, Q-s., Pu, L., and Poo, M-m. 2005. Repeated cocaine exposure facilitates LTP induction in midbrain dopamine neurons Nature 437: 1027-1031.
Engert F., Tao H.W., Zhang L.I., and Poo M-m. 2002. Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons Nature 419: 470-475.
Ganguly, K., Schinder, A.F., Wong, S.T., and Poo, M-m. 2001. GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition Cell 105: 521-532.
