NEUROCHEMICAL DEVELOPMENT OF THE HIPPOCAMPAL REGION IN THE FETAL RHESUS-MONKEY .2. IMMUNOCYTOCHEMISTRY OF PEPTIDES, CALCIUM-BINDING PROTEINS, DARPP-32, AND MONOAMINE INNERVATION IN THE ENTORHINAL CORTEX BY THEEND OF GESTATION

Material for the study came from one 126 day-old rhesus monkey fetus a nd two 3 day-old neonates. The immunocytochemical detection of somatos tatin, neurotensin (NT), parvalbumin, calbindin D-28K, DARPP-32 as wel l as tyrosine hydroxylase (TH), dopamine-beta-hydroxylase and serotoni n (5-HT), was carried out on serial cryostat sections of the entorhina l cortex. The authors reported in a previous paper the precocious diff erentiation of the entorhinal cortex in rhesus monkey fetuses and feat ured the conspicuous expression of calbindin D-28K, somatostatin, neur otensin, and the monoaminergic innervation during the first half of ge station. The present study shows distinct temporal profiles of neuroch emical development during the second half of gestation: the dense neur opeptidergic innervation remained a constant feature; the three aminer gic systems gradually increased in density; parvalbumin, unlike calbin din D-28K, was primarily expressed during the last quarter of gestatio n. Three other prominent features of the last quarter of gestation are illustrated: the refinement of the modular neurochemical organization of the lamina principalis externa, the delayed chemoanatomical develo pment of the rhinal sulcus area, and the establishment of a distinct r ostrocaudal pattern of neurochemical distribution. In correspondence w ith the cluster-like organization of the lamina principalis externa, t he authors observed in the olfactory, rostral, and intermediate fields of the neonate monkey entorhinal cortex, a particular subset of pyram idal-shaped neurons: located in layer III, they were characterized by fasciculated apical dendrites ascending between the cellular islands o f the discontinuous layer II and the coexpression of calbindin D-28K a nd DARPP-32. Besides, most of the other chemical systems displayed a d istinct, area-specific, patchy distribution, except for the homogeneou sly distributed noradrenergic innervation. In the olfactory and rostra l fields, TH positive dopaminergic fibers accumulated on the neuronal islands of layers II-III, and parvalbumin labeled fibers on those of l ayer III, whereas patches of 5-HT and NT-like reactive terminals were segregated between the cellular islands, overlapping the DARPP-32/calb indin D-28 K labeled dendritic bundies. At the opposite, in the interm ediate field, 5-HT positive terminals overlapped the cellular islands of layer II and thin fascicles of dopaminergic fibers ran in the inter island spaces. The somatostatin-LIR innervation was apparently too de nse to reveal a patchy distribution that existed at earlier developmen tal stages. In the caudal field, the patchy pattern was replaced by a predominant bilaminar type of distribution of NT, 5-HT, and TH-like po sitive afferents. Numerous parvalbumin positive multipolar neurons and basket cells participated to a dense parvalbumin labeled network, ext ending through layers II-V, whose partial extrinsic origin is open to discussion. The rhinal sulcus, still reduced to a small dimple at E126 , appeared fully developed at birth. The fundus of the sulcus was mark ed by a sharp decrease of the neurotensin and parvalbumin-LIR innervat ions whereas the density of somatostatin and aminergic terminals incre ased markedly in the perirhinal cortex. Although a transitory overexpr ession of some of the neurochemical systems under study might occur du ring development, their modular organization in the lamina principalis externa of the neonate represents a basic feature of the entorhinal c ortex and adds further support to the evidence that neurons of layers II-III that project to different parts of the hippocampal formation, b elong to distinct heterogeneous systems. This extensive prenatal devel opment is in line with recent data emphasizing the critical role of li mbic structures in early recognition memory in infant monkeys. The que stion arises, however, in view of the delayed development of the rhina l sulcus area, as to whether the preferential connections of the later al entorhinal and perirhinal cortex with regions of polymodal sensory convergence such as the prefrontal cortex and superior temporal gyrus might be established later than the connections of the rest of the ent orhinal cortex.