Neurochemical development of the hippocampal region in the fetal rhesus monkey. II. Immunocytochemistry of peptides, calcium‐binding proteins, DARPP‐32, and monoamine innervation in the entorhinal cortex by the end of gestation
Authors: Berger Brigitte , Alvarez Chantal 
Published: January 2005

Material for the study came from one 126 day‐old rhesus monkey fetus and two 3 day‐old neonates. The immunocytochemical detection of somatostatin, neurotensin (NT), parvalbumin, calbindin D‐28K, DARPP‐32 as well as tyrosine hydroxylase (TH), dopamine‐β‐hydroxylase and serotonin (5‐HT), was carried out on serial cryostat sections of the entorhinal cortex. The authors reported in a previous paper the precocious differentiation of the entorhinal cortex in rhesus monkey fetuses and featured the conspicuous expression of calbindin D‐28K, somatostatin, neurotensin, and the monoaminergic innervation during the first half of gestation. The present study shows distinct temporal profiles of neurochemical development during the second half of gestation: the dense neuropeptidergic innervation remained a constant feature; the three aminergic systems gradually increased in density; parvalbumin, unlike calbindin D‐28K, was primarily expressed during the last quarter of gestation. Three othe 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 development of the rhinal sulcus area, and the establishment of a distinct rostrocaudal pattern of neurochemical distribution. In correspondence with the cluster‐like organization of the lamina principalis externa, the authors observed in the olfactory, rostral, and intermediate fields of the neonate monkey entorhinal cortex, a particular subset of pyramidal‐shaped neurons: located in layer III, they were characterized by fasciculated apical dendrites ascending between the cellular islands of the discontinuous layer II and the coexpression of calbindin D‐28K and DARPP‐32. Besides, most of the other chemical systems displayed a distinct, area‐specific, patcy distribution, except for the homogeneously distributed noradrenergic innervation. In the olfactory and rostral fields, TH positive dopaminergic fibers accumulated on the neuronal islands of layers II‐III, and parvalbumin labeled fibers on those of layer III, whereas patches of 5‐HT and NT‐like reactive terminals were segregated between the cellular islands, overlapping the DARPP‐32/calbindin D‐28 K labeled dendritic bundles. At the opposite, in the intermediate 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 dense to reveal a patchy distribution that existed at earlier developmental stages. In the cadual field, the patchy pattern was replaced by a predominant bilaminar type of distribution of NT, 5‐HT, and TH‐like positive afferents. Numerous parvalbumin positive multipolar neurons and basket cells participated to a dense parvalbumin labeled network, extending 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 marked by a sharp decrease of the neurotensin and parvalbumin‐LIR innervations whereas the density of somatostatin and aminergic terminals increased markedly in the perirhinal cortex. Although a transitory overexpression of some of the neurochemical systems under study might occur during development, their modular organization in the lamina principalis externa of the neonate represents a basic feature of the entorhinal cortex and adds further support to the evidence that neurons of layers II‐III that project to different parts of the hippocampal formation, belong to distinct heterogeneous systems. This extensive prenatal development is in line with recent data emphasizing the critical role of limbic structures in early recognition memory in infant monkeys. The question arises, however, in view of the delayed development of the rhinal sulcus area, as to whether the preferential connections of the lateral entohinal 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 entorhinal cortex.