Hideyuki Cateau

Multiscale analysis of long-term recordings from unanesthetized rats unveils multiple time scales inherent in the neural dynamics

cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), protein kinase G inhibitor KT5823, cGMP analogue 8-bromo-cGMP (8-Br-cGMP), peroxynitrite donor 3-morpholinosydnonimine (SIN-1) or RyR blocker dantrolene for a period of 9–13 DIV. Treatment with L-NAME led to a significant decrease in NO2 level in the culture medium and intracellular cGMP level during the culture for 24 h. L-NAME, ODQ, and KT5823 markedly decreased 5′-bromo-2′-deoxyuridine (BrdU) incorporation into the NPCs the proliferative activity. Contrariwise, SIN-1 significantly increased BrdU incorporation. 8-Br-cGMP partially abolished the decrease in BrdU incorporation by L-NAME. However, no significant change was observed in lactate dehydrogenase released into the culture medium during treatment with any drugs. Treatment with dantrolene was effective in decreasing BrdU incorporation and NO2 level in the culture medium. RT-PCR analysis revealed that there mainly exist RyR3 of RyR1, RyR2, and RyR3 in the NPCs. These results suggest that RyR-mediated Ca2+ release from endoplasmic reticulum is essential for proliferative activity through activation of NO/cGMP pathway in the hippocampal NPCs of embryonic mice.

1301 A state-transition model for LTP and LTD induction

Hideyuki Cateau, Shigeru Tanaka In situ rate constants of CaMKII for phosphorylation triggered by Ca2+ influx from extracellular media and those for dephosphorylation by phosphatases are unknown parameters. Within a biologically plausible range of values of these parameters, we examined phosphorylated states of CaMKII based on the state-transition model, which we have proposed previously. We found that the evolution of enzymatic activity of CaMKII resembles that of synaptic transmission efficacy observed in slice preparation experiments for LTP/LTD induction, when we assumed low intracellular concentration of free Ca2+/calmodulin. Thii resemblance emerges from cooperative interaction among subunits of CaMKII. The blockade of LTD by EGTA could also be reproduced within the same scheme. All these results imply that the amount of enzymatically active CaMKII determines the induction of LTP and LTD.