Proc Natl Acad Sci U S A
November 2009
Neural activity can induce persistent strengthening or weakening of synapses, known as long-term potentiation (LTP) or long-term depression (LTD), respectively. As potential cellular mechanisms underlying learning and memory, LTP and LTD are generally regarded as synapse-specific "imprints" of activity, although there is evidence in vitro that LTP/LTD may spread to adjacent synapses. Here, we report that LTP and LTD induced in vivo at retinotectal synapses of Xenopus tadpoles undergo rapid long-range retrograde spread from the optic tectum to the retina, resulting in potentiation and depression of bipolar cell synapses on the dendrites of retinal ganglion cells, respectively.
View Article and Find Full Text PDFMossy fiber/CA3 long-term potentiation (LTP) is hypothesized to depend on cAMP signals generated by Ca2+-stimulated adenylyl cyclases AC1 or AC8. AC1 gene knock-out mice (AC1-/-) show a partial reduction in mossy fiber LTP, suggesting that either AC8 activity is also critical for mossy fiber LTP or that there is a component of mossy fiber LTP that is independent of CaM-activated adenylyl cyclases. To address this issue, mossy fiber LTP was examined in hippocampal slices from AC8-/- and AC1-/- x AC8-/- double knock-out mice (DKO).
View Article and Find Full Text PDFMyelin-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.
View Article and Find Full Text PDFLong-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell synapses must be balanced by long-term potentiation (LTP) to prevent saturation and allow reversal of motor learning. The only previously analyzed form of cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not nitric oxide. It is a poor candidate to reverse LTD because it is presynaptically expressed whereas LTD is postsynaptic.
View Article and Find Full Text PDFPathfinding 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.
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