ONTOGENY OF QUISQUALATE-ASSOCIATED PHOSPHOINOSITIDE METABOLISM IN VARIOUS REGIONS OF THE RAT NERVOUS-SYSTEM

The effect of postnatal age on phosphoinositide metabolism per se and on quisqualate-stimulated phosphoinositide metabolism was characterize d in synaptoneurosomes prepared from nine different regions of the rat nervous system, namely the brainstem, cerebellum, cerebral cortex, co lliculi, hippocampus, hypothalamus, olfactory bulb, spinal cord and st riatum. In the hippocampus, striatum, cerebellum, cerebral cortex, bra instem, colliculus and spinal cord, the basal levels of inositol phosp hate (inositol-1-phosphate+inositol-4,5-bisphosphate) formation were m aximal two days after birth and declined steeply to steady-state level s from the age of 10 postnatal days. Similarly, in the olfactory bulb, basal inositol phosphate synthesis did not significantly change when measured during the period from postnatal day 10 to 42. The extent of [H-3]-inositol labelling of phosphoinositides as a function of age pre sented similar profiles when measured in hippocampal, striatal, cerebe llar and cerebral cortical synaptoneurosomes, i.e. maximal at perinata l ages and minimal at adult ages. In the hypothalamus, [H-3]-inositol labelling of phosphoinositides showed an increase from postnatal day 1 2 to higher levels from postnatal days 14 to 18 subsequently followed by a dramatic increase from postnatal day 21 to 42. A similar developm ental trend was also obtained for basal inositol phosphate synthesis. On the whole, four types of developmental profiles for quisqualate-sti mulated inositol phosphate formation (expressed as the percentage of t he basal level and as the difference between stimulated and basal leve ls of radioactive inositol phosphates) were obtained depending on the nervous system region studied. In the early, prenatally developed nerv ous system regions, namely the brainstem and the spinal cord, no postn atal stimulation peaks of quisqualate-induced inositol phosphate forma tion were recorded. This was also the case for the colliculi when the stimulation of IP formation was expressed as the difference in basal a nd stimulated levels of inositol phosphates. Secondly, in the olfactor y bulb a region known to possess a continuous capacity for development al plasticity both structurally and functionally during the first thre e weeks of postnatal development, a simultaneous sustained high level of quisqualate stimulation of phosphoinositide metabolism (fluctuating around 200% of the basal level) during the early postnatal period was evident. Thirdly, in regions of the central nervous system like the c erebellum, cerebral cortex, hippocampus and the striatum known to unde rgo intense developmental activity during the first two postnatal week s, peaks of quisqualate-stimulated phosphoinositide metabolism were in itially detected around the first week after birth in each of these br ain areas. Finally, in the hypothalamus where structurally unique post natal developmental processes are known to take place, quisqualate-ind uced inositol phosphate formation progressively increases with age to reach maxima at postnatal day 18. The transient increases in quisquala te responses in the cerebellum, hippocampus and striatum are probably specific to quisqualate since carbachol-stimulated phosphoinositide me tabolism yielded different age-associated response patterns. Similar i ncreases of carbachol- and quisqualate-mediated phosphoinositide hydro lysis were on the Other hand assayed in cerebral cortical and hypothal amic synaptoneurosomes. EC(50), values for quisqualate (the quisqualat e concentration required to produce 50% of the maximal effect) at post natal days 6 and 10 were not significantly different in each of four t ypes of synaptoneurosomes: cerebellar, cerebral cortical, hippocampal and striatal. On the basis of these latter results, it was deduced tha t the peak of quisqualate-stimulated phosphoinositide metabolism does not materialize on the basis of changes in quisqualate metabotropic re ceptor affinity. In conclusion, the measurement of inositol phosphate formation in synaptoneurosomes prepared from different regions of the postnatally developing nervous system indicate that there is a tempora l correlation between the increased activity of quisqualate-stimulated phosphoinositide metabolism mediated by specific metabotropic glutama te receptors and region-specific developmental events. This could sugg est a key role for certain metabotropic glutamate receptors in the dev elopmental plasticity of the nervous system.