Prenatal development of nucleus basalis complex and related fiber systems in man: a histochemical study

To provide parameters for study of the "cholinergic" innervation of a human fetal cerebrum, we have analyzed the prenatal development of histochemical reactivity in the nucleus basalis complex (a magnocellular complex known to contain a high concentration of cholinergic perikarya). Brains from fetuses and premature infants ranging between 8 and 35 weeks of gestation were frozen cut and processed by the thiocholine method for the demonstration of acetylcholinesterase activity. Since no consistent results were obtained with inhibitors on the material younger than 15 weeks, the histochemical reactivity for early stages was expressed as the total cholinesterase reactivity. The first sign of histochemical differentiation of the basal telencephalon is the appearance of a dark cholinesterase reactive "spot" situated between the developing lenticular nucleus and basal telencephalon surface as early as 9 weeks of gestation. The first cholinesterase reactive bundle connects this reactive area (nucleus basalis complex anlage) with the strongly reactive fiber system situated along the dorsal side of the optic tract. During the next "stage" (10.5 weeks), there is a significant increase in the size of the nucleus basalis complex and strongly cholinesterase reactive neuropil occupies the sublenticular, diagonal and septal areas. At this stage we have seen two new cholinesterase-reactive bundles: one well developed cholinesterase reactive fiber stratum approaching (but not penetrating) the neocortical anlage through the external capsule and another minute bundle running towards the medial limbic cortex through the precommissural septum. The supraoptic fiber system can be traced now to the pregeniculate area and the tegmentum. At 15 weeks, the first acetylcholinesterase reactive perikarya appear and the nucleus basalis complex anlage becomes segregated into several strongly reactive territories, corresponding in position to the medial septal, diagonal and basal nuclei as defined on adjacent Nissl stained sections. At this stage, fibers from the nucleus basalis complex enter the "white" matter of frontal, temporal, parietal and occipital parts of the cerebral hemisphere via the external capsule. Between 15 and 18 weeks, acetylcholinesterase fibers spread throughout the "white" matter of the cerebral hemisphere. In the next "stage" (18-22 weeks), strongly reactive fibers can be followed from the nucleus basalis below the putamen and through the external capsule to the transient, synapse-rich subplate zone of frontal, temporal, parietal and occipital cortices.(ABSTRACT TRUNCATED AT 400 WORDS)