Changing numbers of neuronal and non-neuronal cells underlie postnatal brain growth in the rat

Abstract

The rat brain increases >6x in mass from birth to adulthood, presumably through the addition of glial cells and increasing neuronal size, without the addition of neurons. To test this hypothesis, here we investigate quantitatively the postnatal changes in the total number of neuronal and non-neuronal cells in the developing rat brain, and examine how these changes correlate with brain growth. Total numbers of cells were determined with the isotropic fractionator in the brains of 53 Wistar rats, from birth to young adulthood. We find that at birth, >90% of the cells in the rat brain are neurons. Following a dormant period of approximately 3 days after birth, the net number of neurons in the cerebral cortex, hippocampus, and remaining tissue (excluding cerebellum and olfactory bulb) doubles during the first week, then is reduced by 70% during the second postnatal week, concurrently with net gliogenesis. A second round of net addition of 6 million neurons is observed in the cerebral cortex over the following 2 weeks. During the first postnatal week, brain growth relates mainly to increased numbers of neurons of larger average size. In the second and third weeks, it correlates with increased numbers of non-neuronal cells that are smaller in size than the preexisting neurons. Postnatal rat brain development is thus characterized by dramatic changes in the cellular composition of the brain, whose growth is governed by different combinations of cell addition and loss, and changes in average cell size during the first months after birth.

Fig. 1.

Postnatal changes in numbers of neurons and non-neuronal cells in the brain. Each circle represents the number of cells (neurons, filled circles; non-neuronal cells, white circles) found in 1 individual animal. The first postnatal month is shown on the left and the second and third postnatal months are shown on the right with the same Y scale. Periods of net addition of neuronal and non-neuronal cells in each structure are indicated, for reference, in light and dark gray shading, respectively. In the cerebral cortex, hippocampus and rest of brain, numbers of neurons increase significantly between P3 and P7, then decrease until P15. Between P15 and P25, the number of neurons in the cerebral cortex increases again with the net addition of 6 million cells (P < 0.05). Net addition of non-neuronal cells in all structures only begins around P7, once net neuronal addition is over in the cerebral cortex, hippocampus, and RoB.