Cerebellar granule cells are generated postnatally in humans

Abstract

How many cerebellar granule cells are generated pre- or postnatally in human is unknown. Using a rigorous design-based stereologic approach we investigated postmortem cerebella from 14 children who died between the first postnatal day (P1) and 11 months of age (M11). We found a statistically significant (p < 0.05) age-related increase in the total number of granule cells from 5.9 × 10(9) at M1 to 37.6 × 10(9) at M10/11 per cerebellar half but not in the total number of Purkinje cells (12.1 × 10(6) at M1 vs. 13.9 × 10(6) at M10/11 per cerebellar half). Accordingly, approximately 85 % of the cerebellar granule cells are generated postnatally in human, and the number of granule cells per Purkinje cell in the human cerebellum increases from 485 at M1 to 2,700 at M10/11, approximately. These data indicate that the human cerebellum has a much higher functional plasticity during the first year of life than previously thought, and may respond very sensitively to internal and external influences during this time. This has important implications for several neuropsychiatric conditions in which cerebellar involvement has been demonstrated.

The Cellular and Molecular Landscapes of the Developing Human Central Nervous System

“…Substantial numbers of additional neocortical interneurons (Sanai et al, 2011), dentate gyrus neurons (Eriksson et al, 1998), and striatal interneurons (Ernst et al, 2014) are generated after this age, extending postnatally in some instances. On the other hand, 85% of the cerebellar granule cells are generated by the 11 th postnatal month (Kiessling et al, 2014) and the external granule layer disappears by the end of the 18th postnatal month (Raaf and Kernohan, 1944). Thus, the bulk of CNS neurogenesis (i.e., approximately 86.4 billion neurons) occurs over approximately 781 days from 32 pcd to 813 pcd (i.e., approximately 234 prenatal pcd plus 547 postnatal days [birth to the 18 th postnatal month]), which would mean that approximately 4.6 million neurons are generated per hour during the CNS developmental neurogenic period.…”

Maternal investment, life histories, and the evolution of brain structure in primates

“…The cerebellum-life history associations are therefore specifically associated with postnatal development. The postnatal genesis of the majority of cerebellar granule cells followed by synaptogenesis indicates high functional plasticity during this time, making environmental stimuli potentially critical in the shaping of this structure (19). Infancy and juvenility are periods of social learning, practice and play in an environment of reduced risk (40).…”

“…Indeed, the largest proportion of growth in the cerebellum occurs postnatally, within the first two years (18). This is associated with the postnatal proliferation of cerebellar granule cells; 85% of which are generated postnatally (19). The human cerebellum and caudate nucleus are the only structures which show significant positive growth relative to brain size after the first year postnatally (16).…”

Neuronal Activity in Ontogeny and Oncology

“…Functional differentiation of oligodendrocytes to form myelin, or concentric wraps of oligodendrocyte membrane that provide electrical insulation of and metabolic support to axons, are predominantly postnatal processes that span at least the first three decades of human life [249,250]. In contrast to the cerebrum, brainstem and spinal cord, a great deal of cerebellar neuronal development occurs in the early postnatal period, with massive neurogenesis (~38 billion cerebellar granule cells) generated in the first year of human life [251]. Accordingly, cerebellar primitive neuroectodermal tumors, medulloblastomas, are among the most common solid cancers of infancy and early childhood.…”