Interstitial cells of the adult neocortical white matter are the remnant of the early generated subplate neuron population.

The postnatal fate of the first-generated neurons of the cat cerebral cortex was examined. These neurons can be identified uniquely by 3H-thymidine exposure during the week preceding the neurogenesis of cortical layer 6. Previous studies in which 3H-thymidine birthdating at embryonic day 27 (E27) was combined with immunohistochemistry have shown that these neurons are present in large numbers during fetal and early postnatal life within the subplate (future white matter), that they are immunoreactive for the neuron-specific protein MAP2 and for the putative neurotransmitters GABA, NPY, SRIF, and CCK. Here, the same techniques were used to follow the postnatal location and disappearance of the early generated subplate neuron population. At birth (P0), subplate neurons showing immunoreactivity for GABA, NPY, SRIF, or CCK are present in large numbers and at high density within the white matter throughout the neocortex, and the entire population can be observed as a dense MAP2-immunoreactive band situated beneath cortical layer 6. Between P0 and P401 (adulthood), the MAP2-immunostained band disappears so that comparatively few MAP2-immunoreactive neurons remain within the white matter. There is a corresponding decrease in the number and density of neurons stained with antibodies against neurotransmitters. In each instance, these neurons could be double-labeled by the administration of 3H-thymidine at E27, indicating that they are the remnants of the early generated subplate neuron population. The major period of decrease occurs during the first 4 postnatal weeks, and adult values are attained by 5 months. Within the white matter of the lateral gyrus (visual cortex), the density of immunostained neurons decreases dramatically: MAP2, 82%, SRIF, 81%, and NPY, 96%. While SRIF-immunoreactive neurons compose a nearly constant percentage of MAP2-immunoreactive neurons in the white matter between P0 (22%) and P401 (23%), those immunoreactive for NPY decline from 18 to 4%. These changes occur during the same period in which there is less than a twofold increase in white matter area. These observations indicate that the interstitial neurons of the adult neocortical white matter are the oldest neurons of the cerebral cortex since most if not all are derived from the subplate neuron population. In addition, a quantitative analysis suggests that the postnatal decline in subplate neuron density cannot be accounted for solely through dilution by differential growth of the white matter and most likely reflects an absolute decrease in subplate neuron number.(ABSTRACT TRUNCATED AT 400 WORDS)