Cholinergic influences on cortical development and adult neurogenesis

In this review, we focus on immature neurons and their regulation by the cholinergic system, both during cortical development as well as during adult neurogenesis. We discuss various studies that indicate roles for acetylcholine in precursor development and neuronal differentiation. Cholinergic neurons projecting from the basal forebrain innervate the cerebral cortex during critical periods of neuronal development. Acetylcholine stimulation may help to promote a favourable environment for neuronal maturation. Afferents and their cortical target cells interact and are likely to influence each other during the establishment and refinement of connections. Intracortical cholinergic interneurons similarly have a local effect on cortical circuits. Reduced cholinergic innervation during development hence leads to reduced cortical thickness and dendritic abnormalities. Acetylcholine is also likely to play a critical role in neuronal plasticity, as shown in the visual and barrel cortices. Spontaneous nicotinic excitation is also important during a brief developmental window in the first postnatal weeks leading to waves of neural activity, likely to have an effect on neurite extension, target selection and synaptogenesis. In the hippocampus such activity plays a role in the maturation of GABAergic synapses during the developmental shift from depolarizing to hyperpolarizing transmission. The cholinergic system also seems likely to regulate hippocampal neurogenesis in the adult, positively promoting proliferation, differentiation, integration and potentially survival of newborn neurons.