|Budget Amount *help
¥6,800,000 (Direct Cost : ¥6,800,000)
Fiscal Year 1991 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1990 : ¥4,600,000 (Direct Cost : ¥4,600,000)
The serotonin (5-HT) neurons originates from the brain stem of the mammalian central nervous system, widely collaterlize along thier paths, and arborize profusely within most regions, issuing billions of varicose nerve terminals. Now, molecular and functional degenacy of 5-HT receptors and their mutually distinctive regional distributions are clear, and, in pharmacology, 5-HT and related drugs are thought to modulate "the keytone" of an integrated set of functions such as behaviors, motivation, biorhythms, emotion, and so on. Foregoing bases support the sketch of 5-HT system as a divcrgcnt, coherent, mass modulator of higher-order brain functions, and as neuroscience on each neural mechanism develops, this type of integrative issues on the brain would be more and more crucial. To step up the 5-HT issues, however, dynamic features of this system per se and real features of in situ actions of 5-H T, remained unassigned mainly due to inavailability of appropriate methods for perturbation
of the system, and monitoring regional metabolic responses. In the 1991-92 term, we applied a new type, of rapid, selective, extensive and reversibic depletion of brain 5-HT, which had been developed in our lab, and -assessed the metabolic/physiological responses to this efficient perturbation, as representing a set of inverse vectors of inherent 5-HT actions that may be cryptic under normal conditions at dynamic equilibrium. For monitoring brain activities, we applied in vivo microdialysis/microdissection for regional neurotransmitterr turnovers, recordings ofbrain waves, and those of locomotive activities and brain temperature. Our approaches worked well to show essentially coherent nature of regional 5-HT turnouer, its rate, regional responses slow/fast brain waves"with one minute periodicity.
In 1991 school year, we found the multistrata structure of regional neurotransmitter tunovers, and developed approaches to selectively perturb each of them. Some of them were well corelated to temporal perturbation of integrated brain functions. Wc began approaches to cortical 5-HT issues, by 5-HT depletion/cortical response studies and with tetrahydrobiopterin known as a stimulator of amine turnovers Less