Retrosplenial/presubicular continuum in primates: a developmental approach in fetal macaques using neurotensin and parvalbumin as markers

In spite of numerous hodological and neuropsychological studies emphasizing the multimodal connections and integrative functions of the retrosplenial cortex in primates, the precise fate of its caudoventral extent and the composition of the merging area with the hippocampal formation remain a matter of debate. We reported previously how the anlage of the retrosplenial cortex merges with the immature presubicular zone in the fetal rhesus monkey at the end of the first trimester of gestation. In the present study, this caudal area was further defined on a chemoarchitectonic basis, particularly during the late prenatal and perinatal stages, which correspond to the development of the cingulate sulcus and temporal gyri, and the differentiation of the retrosplenial/subicular complex. Neurotensin (NT), a pyramidal cell marker in the limbic cortex, and parvalbumin (PV), a marker of a subset of inhibitory local circuit neurons in the hippocampal formation, were used as immunocytochemical markers. According to distinct chemoarchitectural patterns, (1) areas 29l and 29m of the retrosplenial cortex formed a triangle-shaped ventral expansion which merged with a similar but dorsal expansion of the pre/parasubicular fields. A temporal extension of area 29m down to area TH could not be detected. The pre/parasubiculum contributed with area 29m to the lateral bank of the calcarine sulcus as far as the most caudal extent of the hippocampal formation. (2) The lamina principalis interna of the presubiculum was well individualized and did not appear as a simple horizontal shift of adjoining fields. (3) NT and PV displayed a distinct temporal profile of development. NT was already expressed in the pyramidal cells of the prospective retrosplenial cortex and ventral hippocampal formation at E47 (term 165 days). Major pathways of the hippocampal formation and retrosplenial cortex (fimbria, fornix, angular and cingulum bundles) were progressively labeled indicating early developing projections. A large set of NT-positive afferents reached the retrosplenial cortex between E114 and E120. Their laminar distribution was compatible with a thalamic or a subicular origin. (4) The development of PV expression was delayed until the last quarter of gestation, supporting its proposal as a signal of functional onset. The developmental fate and the particular connections of the presubiculum suggest that its functional importance should be further investigated during infancy and adulthood.