Neurotransmitters in the regulation of neuronal cytoarchitecture.

Recent experiments in isolated neurons in cell culture have demonstrated that neurotransmitters and associated electrical activity can directly affect neurite outgrowth. The results indicate that neurotransmitters have considerable potential to control the development of the neuronal circuits in which they participate in information coding in the adult. Cellular mechanisms regulating growth cone motility have been found to be similar to those regulating neurotransmitter release at the synapse and involve electrical activity, calcium and other second messengers. These similarities suggest that the morphological changes in connections observed in adult plasticity may involve the transition of synaptic terminals back to a growth mode. Excitatory and inhibitory neurotransmitters can interact to yield a net effect on neuronal morphology. In the intact nervous system a balance between these neurotransmitter inputs is probably important in maintaining circuits. Studies of neurotransmitter involvement in learning and memory processes indicate that brain function can alter brain structure and that neurotransmitters may control these structural changes. The hippocampus is one brain region in which we are beginning to define roles for neurotransmitters as sculptors of neuronal cytoarchitecture. The neurotransmitter glutamate was found to specifically affect the cytoarchitecture of hippocampal pyramidal neuron dendrites in a graded manner which suggests that glutamate may be involved in: establishing hippocampal circuitry during brain development; maintaining and modifying circuitry in the adult; and inducing neurodegeneration in several disorders including epilepsy, Alzheimer's disease, and stroke. Therapeutic approaches to disorders which affect brain cytoarchitecture may now be devised based upon knowledge of the neurotransmitters and their cellular mechanisms in the pertinent brain region.