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Mu-ming Poo

Publications and source records attributed to Mu-ming Poo.

10 recordsLinked to original sources
PubMed2003

Reversal and stabilization of synaptic modifications in a developing visual system.

Persistent synaptic modifications are essential for experience-dependent refinement of developing circuits. However, in the developing Xenopus retinotectal system, activity-induced synaptic modifications were quickly reversed either by subsequent spontaneous activity in the tectum or by exposure to random visual inputs. This reversal depended on the burst spiking and activation of the N-methyl-D-aspartate subtype of glutamate receptors. Stabilization of synaptic modifications can be achieved by an appropriately spaced pattern of induction stimuli. These findings underscore the vulnerable nature of activity-induced synaptic modifications in vivo and suggest a temporal constraint on the pattern of visual inputs for effective induction of stable synaptic modifications.

2-Amino-5-phosphonovalerate↗
PubMed2003

Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications.

Information processing in the neuron requires spatial summation of synaptic inputs at the dendrite. In CA1 pyramidal neurons of the hippocampus, a brief period of correlated pre- and postsynaptic activity, which induces long-term potentiation (LTP) or long-term depression (LTD), results in a persistent increase or decrease in the linearity of spatial summation, respectively. Such bidirectional modification of the summation property is specific to the modified input and reflects localized dendritic changes involving I(h) channels and NMDA receptors. Thus, correlated pre- and postsynaptic activity alters not only the strength of the activated input but also its dendritic integration with other inputs.

Animals↗
PubMed2003

Signalling and crosstalk of Rho GTPases in mediating axon guidance.

Axon extension during development of the nervous system is guided by many factors, but the signalling mechanisms responsible for triggering this extension remain mostly unknown. Here we have examined the role of Rho family small guanosine triphosphatases (GTPases) in mediating axon guidance by diffusible factors. Expression of either dominant-negative or constitutively active Cdc42 in cultured Xenopus laevis spinal neurons, at a concentration that does not substantially affect filopodial formation and neurite extension, abolishes the chemoattractive growth cone turning induced by a gradient of brain-derived neurotrophic factor that can activate Cdc42 and Rac in cultured neurons. Chemorepulsion induced by a gradient of lysophosphatidic acid is also abolished by the expression of dominant-negative RhoA. We also show that an asymmetry in Rho kinase or filopodial initiation across the growth cone is sufficient to trigger the turning response and that there is a crosstalk between the Cdc42 and RhoA pathways through their converging actions on the myosin activity essential for growth cone chemorepulsion.

Animals↗
PubMed2002

Localized synaptic potentiation by BDNF requires local protein synthesis in the developing axon.

Brain-derived neurotrophic factor (BDNF) is known to promote neuronal survival, guide axonal pathfinding, and participate in activity-dependent synaptic plasticity. In Xenopus nerve-muscle cultures, localized contact of a single BDNF-coated bead with the presynaptic axon resulted in potentiation of transmitter secretion at the developing synapses, but only when the bead was placed within 60 microm from the synapse. The localized potentiation induced by BDNF is accompanied by a persistent local elevation of [Ca(2+)](i) in the axon and requires constitutive presynaptic protein translation, even for axons severed from the cell body. Thus, presynaptic local TrkB signaling and protein synthesis allow a localized source of BDNF to potentiate transmitter secretion from nearby synapses, a property suited for spatially restricted synaptic modification by neurotrophins.

Acetylcholine↗
PubMed2002

Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons.

During development of the visual system, the pattern of visual inputs may have an instructive role in refining developing neural circuits. How visual inputs of specific spatiotemporal patterns shape the circuit development remains largely unknown. We report here that, in the developing Xenopus retinotectal system, the receptive field of tectal neurons can be 'trained' to become direction-sensitive within minutes after repetitive exposure of the retina to moving bars in a particular direction. The induction of direction-sensitivity depends on the speed of the moving bar, can not be induced by random visual stimuli, and is accompanied by an asymmetric modification of the tectal neuron's receptive field. Furthermore, such training-induced changes require spiking of the tectal neuron and activation of a NMDA (N-methyl-D-aspartate) subtype of glutamate receptors during training, and are attributable to an activity-induced enhancement of glutamate-mediated inputs. Thus, developing neural circuits can be modified rapidly and specifically by visual inputs of defined spatiotemporal patterns, in a manner consistent with predictions based on spike-time-dependent synaptic modification.

Animals↗
PubMed2002

Adaptation in the chemotactic guidance of nerve growth cones.

Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.

Adaptation, Biological↗
PubMed2002

A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth.

Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases.

Animals↗
PubMed2002

Nerve growth cone guidance mediated by G protein-coupled receptors.

Growing axons navigate by responding to chemical guidance cues. Here we report that growth cones of rat cerebellar axons in culture turned away from a gradient of SDF-1, a chemokine that attracts migrating leukocytes and cerebellar granule cells via a G protein-coupled receptor (GPCR). Similarly, Xenopus spinal growth cones turned away from a gradient of baclofen, an agonist of the GABA(B) receptor. This response was mediated by G(i) and subsequent activation of phospholipase C (PLC), which triggered two pathways: protein kinase C (PKC) led to repulsion, and inositol 1,4,5-triphosphate (IP(3)) receptor activation led to attractive turning. Under normal culture conditions, PKC-dependent repulsion dominated, but the repulsion could be converted to attraction by inhibiting PKC or by elevating cytosolic cGMP. Thus, GPCRs can mediate both repulsive and attractive axon guidance in vitro, and chemokines may serve as guidance cues for axon pathfinding.

Aminocaproic Acid↗
PubMed2002

A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein.

Myelin-associated glycoprotein (MAG), an inhibitor of axon regeneration, binds with high affinity to the Nogo-66 receptor (NgR). Here we report that the p75 neurotrophin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling. In cultured human embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular Ca2+ elevation. Co-immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody against p75(NTR) (NGFR5), and extensive coexpression was observed in the developing rat nervous system. Furthermore, NGFR5 abolished MAG-induced repulsive turning of Xenopus axonal growth cones and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells. Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.

Animals↗