Ontogeny of the human central nervous system: What is happening when?

Abstract

The present paper reviews current data on the structural development of the human nervous system. Focus is on the timing of ontogenetic events in the telencephalon. Neuronal proliferation and migration especially occur during the first half of gestation; the second half of gestation is the period of the existence of the functionally important transient structure ‘subplate’ and the major period of glial cell proliferation and programmed cell death. Axon and dendrite sprouting and synapse formation bloom during the last trimester of gestation and the first postnatal year. Major part of telencephalic myelination occurs during the first year after birth. Many developmental processes, such as myelination, synapse formation and synapse elimination continue throughout childhood and adolescence. Evidence is emerging that the peak of synapse elimination occurs between puberty and the onset of adulthood. Neurotransmitter systems are present from early foetal life onwards and their pre- and perinatal development is characterized by periods of transient overexpression. The latter is for instance true for the acetylcholinergic, catecholaminergic and glutamate systems. Thus, the development of the human brain is characterized by a protracted, neatly orchestrated chain of specific ontogenetic events. The continuous changes of the nervous system have consequences for vulnerability to adverse conditions, for diagnostics and for physiotherapeutical intervention.

Introduction

The development of the central nervous system (CNS) is a complex and long-lasting process—this can be read in many textbook chapters (e.g., [1], [2]). The aim of the present review is to assess as accurately as possible when specific events take place during ontogeny of the human nervous system. Knowledge on the exact timing of ontogenetic events during human brain development will shed light on the mechanisms playing a role in the determination of sequelae after adversities occurring at a specific point in time during brain development (excellently reviewed in Ref. [1]). Knowledge on the timing of developmental processes in the human nervous system is also pertinent for the development of appropriate neurological assessment techniques and for the interpretation of neurological findings at early age. It might also facilitate our understanding of the timing of intervention in infants at high risk for or with developmental disorders. For the timing of early intervention it is generally assumed that ‘earlier is better’ [3], but a recent review on the effect of early intervention in ‘high-risk’ infants indicated that this is not necessarily the case [4].

In the present review, we based ourselves predominantly on human data. For the missing links, we preferably used non-human primate data; when such data were not available, rodent data were used. We zoomed in on ontogenetic events in the telencephalon, i.e., the major neural determinant of human behaviour. In order to facilitate the understanding of the timing of the various events we included a schematic timetable of the various developmental processes (Fig. 1).