Synaptic Clefts Are Made to Be Crossed: Neurotransmitter Signaling in the Central Nervous System

The primary means of communication between neurons in the mammalian central nervous system (CNS) is via release of chemical transmitters. Although the first transmitters to be discovered were the biogenic amines, such as acetylcholine and norepinephrine, involved in transmission in the autonomic nervous system, the contribution of other types of transmitters, such as amino acids and peptides, to CNS transmission has been the subject of recent study. Part of this interest stems from the relatively large percentage of neuronal connections that make use of amino acid transmitters such as gamma-aminobutyric acid and glutamate and also from the tremendous diversity possible when peptides are used as transmitters. Several disorders of CNS transmission are related to the degeneration of neuronal pathways in the brain. Two of the most prevalent neurologic disorders that result from degeneration are Alzheimer's and Parkinson's diseases. Aspects of these disorders related to chemical neurotransmission are discussed, along with implications with regard to therapeutic strategies. Functions of and possible abnormalities in amino acid transmission that may be associated with CNS disorders are examined. Several peptides are postulated to play a role in neurotransmission and concepts regarding the significance of the coexistence and release of biogenic amines and peptides at the same neuronal terminals are presented.