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R Douglas Fields

Publications and source records attributed to R Douglas Fields.

20 records · Page 2Linked to original sources

Somatic action potentials are sufficient for late-phase LTP-related cell signaling.

A question of critical importance confronting neuroscientists today is how biochemical signals initiated at a synapse are conveyed to the nucleus. This problem is particularly relevant to the generation of the late phases of long-term potentiation (LTP). Here we provide evidence that some signaling pathways previously associated with late-LTP can be activated in hippocampal CA1 neurons without synaptic activity; somatic action potentials, induced by backfiring the cells, were found to be sufficient for phosphorylation of extracellular signal-regulated kinase-1/2 and cAMP response element-binding protein, as well as for induction of zif268. Furthermore, such antidromic stimulation was adequate to rescue "tagged" synapses (early-LTP) from decay. These results show that a synapse-to-nucleus signal is not necessary for late-phase LTP-associated signaling cascades in the regulation of gene expression.

Action Potentials↗

Regulation of the cell cycle in normal and pathological glia.

Precise regulation of the glial cell cycle is essential during nervous system development and in response to injury, whereas disruption of cell cycle control is associated with malignant glial tumors and other nervous system diseases. The Ras signaling pathway plays a central role in regulating the mammalian cell cycle, and uncontrolled Ras signaling has been implicated in a wide range of human cancers, including malignant gliomas. Recent studies in glia have demonstrated that activation of Ras can either induce or inhibit proliferation through complex interactions among downstream signaling pathways impinging on cell cycle regulatory proteins. Studies in Schwann cells have begun to delineate the pathways by which Ras regulates the cell cycle in normal and pathological glia, and have identified promising targets for therapeutic intervention in the treatment of PNS and CNS malignant glial tumors.

Animals↗