METABOTROPIC GLUTAMATE RECEPTORS ARE DIFFERENTIALLY REGULATED DURING DEVELOPMENT

The postnatal expression of metabotropic glutamate receptors was studi ed in rat brain by in situ hybridization and autoradiographic binding techniques. The messenger RNAs encoding five metabotropic glutamate re ceptor subtypes named mGluR1-5 had distinct regional and temporal expr ession profiles. mGluR1, mGluR2 and mGluR4 messenger RNA expression wa s low at birth and increased during postnatal development. In contrast , mGluR3 and mGluR5 were highly expressed at birth and decreased durin g maturation to adult levels of expression. [H-3]Glutamate binding com petition studies in developing brain disclosed the presence of two typ es of binding sites with the pharmacological properties of metabotropi c glutamate receptors, having high (metabotropic type-1 binding sites; K-1 = 8 nM) and low affinity (metabotropic type-2 binding sites; K-1 = 50 mu M) for quisqualic acid, as in adult rat brain. The densities o f metabotropic binding sites changed during development in a complex, regionally specific fashion. Metabotropic type-1 binding sites were pr esent at low levels at birth and gradually increased during the second postnatal week. In the striatum, globus pallidus and cerebellar granu le layer, the increase in density of metabotropic type-1 binding sites was transient but persisted in the cerebellar molecular layer. In con trast, metabotropic type-2 binding sites were present at high densitie s in most regions in the first postnatal week and decreased during the second and third week, particularly in the thalamic reticular nucleus and globus pallidus. Only in the external cortex did both metabotropi c type-1 and metabotropic type-2 binding sites increase during develop ment. A striking correspondence between the temporal pattern of expres sion of specific metabotropic glutamate receptor transcripts and metab otropic binding sites was observed in the reticular nucleus of the tha lamus (mGluR3; metabotropic type-2 binding sites) and cerebellum (mGlu R1; metabotropic type-1 binding sites) suggesting early translation of these metabotropic glutamate receptor messenger RNAs into receptor pr oteins. In other regions the relationship between messenger RNA expres sion and binding sites was less direct: comparison between expression of metabotropic glutamate receptor messenger RNA and binding sites sug gests both a pre- and postsynaptic location of some receptor subtypes. These data imply a functional role of mGluR3 and mGluR5 during synapt ogenesis and maintenance of adult synapses and of mGluR1, mGluR2 and m GluR4 in mature synaptic transmission.