THE JOURNAL zyxwvu OF COMPARATIVE NEUROLOGY 355~81-92 (1995) Postnatal Maturation of GABA-Immunoreactive Neurons of Rat Medial Prefrontal Cortex STEPHEN L. VINCENT, LAURIE PABREZA, AND FRANCINE M. BENES Department of Psychiatry (S.L.V., F.M.B.) and Program in Neuroscience (F.M.B.), Harvard Medical School, Boston, Massachusetts 02115; Mailman Research Center, Laboratory for Structural Neuroscience, McLean Hospital, Belmont, Massachusetts 02178 (S.L.V.,L.P.,F.M.B.). ABSTRACT A light microscopic immunocytochemical approach has been used to examine the distribu- tion and maturation of y-aminobutyric acid- (GABA) containing cells in rat medial prefrontal cortex (mPFC) at progressive postnatal stages. Between P1 and P5, labeled cells in the cortical plate show less differentiated morphological characteristics when compared to cells in the deeper laminae. By P10, however, most labeled cells in superficial laminae show more differentiated characteristics with some having a distinctive multipolar appearance. Between P1 and P5, there is a significant increase (50%) in the density of GABA-containing cells in the superficial laminae, while concurrently there is an overall decrease in the subjacent deeper laminae. zyxwvutsr As the cortex continues to expand, there is a corresponding decrease in the density of GABA-immunoreactive cells in the outer two-thirds of the cortical mantle until approximately P15, stabilizing at 20-25 cells/100,000 km2 for all laminae. Between P1 and P15, there is also a significant increase (133%)in the average size of labeled cells, followed by a gradual decrease of 30% between P15 and P41. During P1-7, there is a marked increase in the density of labeled axosomatic terminals in both the superficial (200%)and deep laminae (116%).In the superficial layers, however, the density of labeled terminals again increases by 86% between P12 and P18. In general, the present findings are consistent with the idea that there is a progressive maturation of the intrinsic GABAergic system in rat mPFC in a classic “inside-out” pattern, and this involves extensive postnatal changes occurring during the first zyxw 3 postnatal weeks. zyxwvuts o 1995 Wiley-Liss, Inc. Indexing terms: interneurons, limbic cortex, cortical development, axosomaticterminals, immunocytochemistry The neurogenesis, neuronal migration, and maturation of neurons in the developing mammalian cerebral cortex have been the subject of intensive study (reviewed in Sidman and Rakic, 1973; Rakic, 1977; Miller, 1988). During the past decade, the availability of methods to localize a variety of markers associated with central neurotransmit- ters has made it feasible to characterize the ontogenetic development of different subpopulations of neurons in the developing brain (Parnavelas et al., 1988). One such trans- mitter is y-aminobutyric acid (GABA),the principal inhibi- tory neurotransmitter in the neocortex (Emson and Lind- vall, 1979; Kmjevic, 1984), which is localized to intrinsic nonpyramidal neurons (Houser et al., 1984) distributed throughout the cortical layers (Parnavelas et al., 1977; Peters, 1985).During prenatal development, GABA concen- trations in the cortical anlage are moderately high (Coyle and Enna, 1976; Coyle, 1982).Although GABA-containing cells are present throughout various prenatal and postnatal stages of cortical development (Chronwall and Wolff, 1980; Wolff et al., 1984; Lauder et al., 1986; Huntley et al., 1988; Seress and Ribak, 1988; Fosse et zyx al., 1989; Chun and Shatz, 1989; Van Eden et al., 1989; Cobas et al., 1991; Huntley and Jones, 1991; Parnavelas, 1992; Schwartz and Meinecke, 1992), they are generated during a relatively narrow win- dow between embryonic days (E) 14 and 21 (Miller, 1985, 1988; Van Eden et al., 1989; Cobas et al., 1991). Their migration proceeds in an “inside-out” pattern, similar to that described for projection neurons (Miller, 1986). Inter- estingly, GABA appears transiently in some cells that Accepted August 30,1994. Address reprint requests to Dr. Francine M. Benes, Laboratory for Structural Neuroscience, Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02178. zyxwv o 1995 WILEY-LISS, INC.