Development of neurotransmitter systems during critical periods.

Neurotransmitters are released from neurons and mediate neuronal communication. Neuromodulators can also be released from other cells and influence the neuronal signaling. Both neurotransmitters and neuromodulators play an important role in the shaping and the wiring of the nervous system possibly during critical windows of the development. Monoamines are expressed in the very early embryo, at which stage the notochord already contains high noradrenaline levels. Purines and neuropeptides are probably also expressed at an early stage, in a similar way as they occur during early phylogenesis. The levels of most neurotransmitters and neuromodulators increase concomitantly with synapse formation. Some of them surge during the perinatal period (such as glutamate, catecholamines, and some neuropeptides) and then level off. The interesting question is to what extent the expression of neuroactive agents is related to the functional state of the fetus and the newborn. Monoamines are expressed in the very early embryo, at which stage the notochord already contains high noradrenaline levels. They may have an important role for neurotransmission in the fetus. In the adult mammal, the fast switching excitatory amino acids dominate. However, they also seem to be important for the wiring of the brain and the plasticity before birth. NMDA receptors that are supposed to mediate these effects dominate and are then substituted by AMPA receptors. The main inhibitory amino acids gamma-aminobutyric acid (GABA) and glycine are excitatory in the developing brain by depolarizing developing neurons that have high Cl- concentrations. This seems to be of major importance for the wiring of neuronal circuits. Prenatal or neonatal stress, for example, hypoxia, can affect the programming of neurotransmitter and receptor expression, which can lead to long-term behavioral effects.