Expression of calcium/calmodulin-dependent protein kinase in relation to dopamine islands and synaptic maturation in...

During pre- and postnatal development the dopamine-containing nigrostriatal afferents of the striatum are arranged as a conspicuous series of patches (the "dopamine islands"). The development of this dopamine island system, which metamorphoses in early postnatal life to the striosomal architecture of the adult, has recently received considerable attention, but the factors initiating and influencing maturation of this architecture are largely unknown. In an attempt to clarify the relationships between the onset of clustering of dopamine-containing afferents, the grouping of neurons within future striosomes and the maturation of synapses in the striatum, we compared the initial prenatal appearance and subsequent development of immunohistochemical markers for the dopamine-containing innervation [tyrosine hydroxylase (TH)-like immunoreactivity], for synaptic vesicles (SV48-like immunoreactivity), and for a phosphorylation-related enzyme Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II-like immunoreactivity) that is expressed in virtually all striatal neurons by adulthood. Here we present evidence that during striatal ontogeny, both neurons and neuropil expressing CaM kinase II-like immunoreactivity and SV48-positive terminals form discrete patches that are in register with dopamine islands. It is CaM kinase II-positive elements, however, rather than the TH-positive island fibers (or SV48-positive synapses), that initially form overt clusters. Dopamine-containing fibers begin to innervate the striatal anlage just prior to embryonic day (E) 32. Their distribution follows the general lateral to medial developmental gradient characteristic of the striatum but is not yet distinctly islandic. At this time, CaM kinase II-like immunoreactivity was very weak or not present at all and SV48-like immunoreactivity was undetectable. By E36, CaM kinase II-positive neurons are visible in discrete patches of immunopositive neuropil, but only faint inhomogeneities are detectable in the distribution of TH-positive fibers and scarcely any SV48-like immunoreactivity can be seen. By E45, all 3 markers are focused in typical islandic patterns, and they remain so into the early postnatal period. These observations suggest a developmental sequence in which dopamine-containing fibers invade the striatal anlage prior to forming distinct islandic foci and prior to the maturational events signaled by the production of CaM kinase II within the neurons and neuropil of future striosomes.(ABSTRACT TRUNCATED AT 400 WORDS)