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Activity-dependent Regulation (activity-dependent + regulation)
Selected AbstractsActivity-dependent regulation of synaptic size in Drosophila neuromuscular junctionsDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2006Hiroaki Nakayama Abstract One of the fundamental questions in neural development is how neurons form synapses of the appropriate size for the efficient transfer of information across neural circuits. Here we investigated the mechanisms that bring about the size correlation between synapses and postsynaptic cells during development of Drosophila neuromuscular junctions (NMJs). To do this, we made use of a unique system in which two neighboring muscles (M6 and M7) are innervated by the same neurons. In mature NMJs, synaptic size on M6 is normally larger than that on M7, in accordance with the difference in muscle volume; this ensures the same extent of contraction of both muscles, and we refer to this correspondence as "matching". We found that matching was apparent in larvae 8 h after hatching, but not in newly hatched larvae despite the difference in muscle volume. When sensory inputs were suppressed by the expression of tetanus toxin in sensory neurons, matching did not occur, although synapses were able to grow. Matching was also suppressed by the inhibition of motoneuronal activity. These results suggest that matching is induced by regulating the rate of synaptic growth on M6 and M7 in an experience- and activity-dependent manner. It seems most likely that retrograde signals from the postsynaptic to the presynaptic cell convey the information about muscle cell size. We thus examined whether a candidate of retrograde signaling in NMJs, BMP signaling, is involved inmatching. However, there was no effect on matching inBMP type II receptor gene mutants, suggesting thatother experience-driven mechanisms besides BMP signaling are involved in the proper development of synapses. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell lineTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006William J. Brackenbury We have shown previously that voltage-gated Na+ channels (VGSCs) are up-regulated in human metastatic disease (prostate, breast and small-cell lung cancers), and that VGSC activity potentiates metastatic cell behaviours. However, the mechanism(s) regulating functional VGSC expression in cancer cells remains unknown. We investigated the possibility of activity-dependent (auto)regulation of VGSC functional expression in the strongly metastatic Mat-LyLu model of rat prostate cancer. Pretreatment with tetrodotoxin (TTX) for 24,72 h subsequently suppressed peak VGSC current density without affecting voltage dependence. The hypothesis was tested that the VGSC auto-regulation occurred via VGSC-mediated Na+ influx and subsequent activation of protein kinase A (PKA). Indeed, TTX pretreatment reduced the level of phosphorylated PKA, and the PKA inhibitor KT5720 decreased, whilst the adenylate cyclase activator forskolin and the Na+ ionophore monensin both increased the peak VGSC current density. TTX reduced the mRNA level of Nav1.7, predominant in these cells, and VGSC protein expression at the plasma membrane, although the total VGSC protein level remained unchanged. TTX pretreatment eliminated the VGSC-dependent component of the cells' migration in Transwell assays. We concluded that the VGSC activity in Mat-LyLu rat prostate cancer cells was up-regulated in steady-state via a positive feedback mechanism involving PKA, and this enhanced the cells' migratory potential. [source] Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer diseaseHIPPOCAMPUS, Issue 10 2009Sebastian Mirochnic Abstract An active lifestyle is to some degree protective against Alzheimer's disease (AD), but the biological basis for this benefit is still far from clear. We hypothesize that physical and cognitive activity increase a reserve for plasticity by increasing adult neurogenesis in the hippocampal dentate gyrus (DG). We thus assessed how age affects the response to activity in the murine APP23 model of AD compared with wild type (WT) controls and studied the effects of physical exercise (RUN) and environmental enrichment (ENR) in comparison with standard housing (CTR) at two different ages (6 months and 18 months) and in both genotypes. At 18 months, both activity paradigms reduced the hippocampal human A,1-42/A,1-40 ratio when compared with CTR, despite a stable plaque load in the hippocampus. At this age, both RUN and ENR increased the number of newborn granule cells in the DG of APP23 mice when compared with CTR, whereas the levels of regulation were equivalent to those in WT mice under the same housing conditions. At 6 months, however, neurogenesis in ENR but not RUN mice responded like the WT. Quantifying the number of cells at the doublecortin-positive stage in relation to the number of cells on postmitotic stages we found that ENR overproportionally increased the number of the DCX-positive "late" progenitor cells, indicative of an increased potential to recruit even more new neurons. In summary, the biological substrates for activity-dependent regulation of adult hippocampal neurogenesis were preserved in the APP23 mice. We thus propose that in this model, ENR even more than RUN might contribute to a "neurogenic reserve" despite a stable plaque load and that age affects the outcome of an interaction based on "activity." © 2009 Wiley-Liss, Inc. [source] The Kv4.2 mediates excitatory activity-dependent regulation of neuronal excitability in rat cortical neuronsJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Bin Shen Abstract Neuronal excitability can cooperate with synaptic transmission to control the information storage. This regulation of neuronal plasticity can be affected by alterations in neuronal inputs and accomplished by modulation of voltage-dependent ion channels. In this study, we report that enhanced excitatory input negatively regulated neuronal excitability. Enhanced excitatory input by glutamate, electric field stimulation or high K+ increased transient outward K+ current, whereas did not affect the delayed rectifier K+ current in rat cultured cortical neurons. Both the voltage-dependent K+ channel 4.2 and 4.3 subunits contributed to the increase. The increase in the K+ current density by Kv4.2 was ascribed to its cytoplasmic membrane translocation, which was mediated by NMDA type of glutamate receptor. Furthermore, enhanced excitatory input inhibited neuronal excitability. Taken together, our results suggest that excitatory neurotransmission affects neuronal excitability via the regulation of the K+ channel membrane translocation. [source] | ||||||||||