Spatial-temporal topography in neurogenesis of the macaque thalamus

Maternal injection of ³H-thymidine ([³H]dT) during gestation in non-human primates (NHPs) has been used to determine the time of neurogenesis for various brain areas, including the lateral geniculate (LGN) and the pulvinar (PUL) nuclei of the caudal thalamus. Here, we examine neurogenesis in the rostral thalamus, with focus on the mediodorsal (MD) and the anterior nuclei (ANT), to determine if neurogenesis of rostral and caudal thalamic nuclei is concurrent or instead temporally staggered. The MacBrainResource (MBR) search function identified archived cases (N = 10) of [³H]dT labeled specimens, with injection dates ranging from embryonic day 25 (E25)-E50 and postnatal sacrifice dates. Slides were scanned to create digital images for subsequent analysis using Stereo Investigator software. Labeled neurons were mapped within a contour that encompassed the entire rostral thalamus. These maps were superimposed onto closely corresponding sections from the online BrainMaps macaque atlas to facilitate analysis. Our novel approach uncovered a previously undetected spatial-temporal patterning of neurogenesis in the thalamus. At E30, labeled neurons were located in a compact medial band; at E38-E40, labeling was dense ventrolaterally, and at E43, labeling predominated laterally at rostral levels and was widely distributed at caudal levels. Peak neurogenesis occurs earlier in MD (E30-E43) and ANT (E31-E43) than in LGN (E36-E43) and PUL (E36-E45). Birth-dating of neurons in MD and ANT, two higher order relay nuclei implicated in the pathology of schizophrenia, provides further insight into the critical period of vulnerability during which early developmental perturbation may increase incidence of schizophrenia later in life.