Biomedical subjects

Chien-ping Wu

Publications and source records attributed to Chien-ping Wu.

4 recordsLinked to original sources

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.

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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↗

PubMedDate not supplied

GDNF acutely potentiates Ca2+ channels and excitatory synaptic transmission in midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) is best known for its long-term survival effect on dopaminergic neurons in the ventral midbrain. A recent study showed that acute application of GDNF to these neurons suppresses A-type potassium channels and potentiates neuronal excitability. Here we have characterized the acute effects of GDNF on Ca(2+) channels and synaptic transmission. GDNF rapidly and reversibly potentiated the high voltage-activated (HVA) Ca(2+) channel currents in cultured dopaminergic neurons. Analyses of channel kinetics indicate that GDNF decreased the activation time constant, increased the inactivation and deactivation time constants of HVA Ca(2+) channel currents. Ca(2+) imaging experiments demonstrate that GDNF facilitated Ca(2+) influx induced by membrane depolarization. To investigate the physiological consequences of the Ca(2+) channel modulation, we examined the acute effects of GDNF on excitatory synaptic transmission at synapses made by these dopaminergic neurons, which co-release the transmitter glutamate. Within 3 min of application, GDNF increased the amplitude of spontaneous and evoked excitatory autaptic- or multiple-postsynaptic currents. The frequency as well as the amplitude of miniature excitatory postsynaptic currents was also increased. These results reveal, for the first time, an acute effect of GDNF on synaptic transmission and its potential mechanisms, and suggest that an important function of GDNF for midbrain dopaminergic neurons is the acute modulation of transmission and ion channels.

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