Development of Central Neurotransmitter Systems

Inter-neuronal communication is mediated primarily by chemical neurotransmitters, which are released from the nerve terminal, diffuse across the synaptic cleft and interact with specific receptors on adjacent neurons. The development of the biochemical machinery for neurotransmission is closely linked to the functional maturation of the brain's neuronal circuitry. Components essential for neurotransmission (e.g., synthetic enzymes, endogenous neurotransmitters, re-uptake processes and receptors) serve as specific biochemical markers for neuronal systems. The appearance of and developmental increases in these markers during fetal and postnatal life occur with the cessation of neuronal replication and initiation of neuropil elaboration. Discrete groups of neurotransmitter-specific neurons develop according to different timetables, resulting in a shifting pattern of their relative influence in the maturing brain. Human and animal studies demonstrate an early innervation of the neocortex by catecholaminergic axons while neurons using gamma-aminobutyric acid (GABA) mature somewhat later; and the ontogeny of the acetylcholine neurons lags behind both of these. Within each neuronal group the individual biochemical components for neurotransmission also follow differing time courses of maturation. Animal studies, in which cortical neurons were ablated by administering a toxin to the fetus, illustrate the interplay between intrinsic programmes and environmental influences in the assembly of neuronal circuits. The brain's preparation for independent life is characterized by a continual reorganization of neurotransmitter pathways.