Cortical bitufted, horizontal, and Martinotti cells preferentially expressand secrete reelin into perineuronal nets, nonsynaptically modulating geneexpression

Reelin (Reln) is a protein with some structural analogies with other extrac ellular matrix proteins that functions in the regulation of neuronal migrat ion during the development of cortical laminated structures. In the cortex of adult animals, Rein is expressed primarily in gamma-aminobutyric acid (G ABA)ergic neurons and is secreted into perineuronal nets. However, only 50- 60% of GABAergic interneurons express Rein. We have characterized this subp opulation of cortical GABAergic neurons that expresses Rein by using two st rategies: (i) a double immunolabeling procedure to determine the colocaliza tion of Rein with neuropeptides and Ca2+-binding proteins and (ii) a combin ation of Golgi staining and Rein immunolabeIing to determine the morphology of the rat cortical cells that store Rein, Many interneurons that express Neuropeptide Y (NPY) or somatostatin (but none of those that express parval bumin) are Reln-immunopositive, A small population of calbindin-positive in terneurons and very few calretinin-positive cells express Rein immunopositi vity. Golgi staining revealed that layer I horizontal cells, layer Il-V bit ufted neurons, and some deep cortical layer Martinotti cells express Rein. Basket and chandelier cells are often immunopositive to parvalbumin, but ne ver to Rein, Although Rein is secreted by GABAergic neurons, its target are not the GABA receptors, but rather may be extrasynaptically located in per ineuronal nets and concerned with the modulation of neuronal plasticity, Da b1, the target adapter protein that presumably mediates transcription regul ation via the extrasynaptic actions of Rein, is expressed predominantly in pyramidal neurons, but it can also be detected in a small population of GAB Aergic neurons that are neither horizontal nor bitufted neurons.