Ultrastructural localization of calbindin-D28k and GABA in the matrix compartment of the rat caudate-putamen nuclei.

The calcium binding protein, Calbindin-D28k, is known to be localized within spiny neurons of the matrix of the dorsal striatum, caudate-putamen nuclei. This compartment is also known to contain an abundance of GABAergic neurons and to receive extensive input from excitatory limbic and cortical afferents whose activation produces rapid influxes of calcium in neuronal targets. We used electron microscopic immunocytochemistry to examine a potential role for calbindin in GABAergic neurons in the caudate-putamen nuclei. Sections of striatal tissue from acrolein-fixed adult rat brains were dual-labeled using immunoperoxidase for the localization of rabbit anti-calbindin and immunogold-silver for the localization of rat anti-GABA antibodies. Calbindin-D28k and GABA were mainly co-localized in somata and large dendrites. The peroxidase reaction product for calbindin was diffusely distributed throughout the neuronal cytoplasm, but appeared more densely localized along asymmetric, excitatory-type, postsynaptic junctions of dendritic spines, as well as saccules of smooth endoplasmic reticulum near dendritic appositions. In contrast, the immunogold-silver labeling for GABA was largely restricted to perikarya and large dendrites. Axon terminals forming symmetric junctions were also sometimes dual-labeled for calbindin and GABA. However, the majority of the calbindin-immunoreactive terminals did not contain GABA and many formed asymmetric excitatory-type synapses with either unlabeled or calbindin-labeled dendritic spines. These results suggest that, in the striatal matrix, Calbindin-D28k contributes to the immobilization of calcium (i) in selectively activated postsynaptic spines of GABAergic and possibly non-GABAergic neurons and (ii) in terminals containing GABA as well as other excitatory and inhibitory transmitters. The extent to which calbindin is able to restrict the cytosolic increases in calcium to selective sites of utilization in these neurons may have important consequences for normal synaptic function and for neuroprotection against excitoxicity.