Neurotransmitters

The nervous system processes sensory information and controls behavior by performing an enormous number of computations. These computations occur both within cells and between cells, but it is intercellular information processing, involving complex neural networks, that provides the nervous system with its remarkable functional capacity. The principal cells involved in information processing are neurons, of which there are hundreds, if not thousands of individual cell types based on morphology, location, connectivity and chemistry [1]. In addition to neurons, the other major kind of cell in the nervous system is the glia, which play critical support roles, but which are increasingly seen to function in some aspects of information processing. To provide some idea of the magnitude of the information processing capacity of the human brain, its 1011 neurons make, on average, about 1000 connections or synapses, at which communication occurs with other neurons. The range of synapses per cell is very large; the Purkinje cells of the cerebellum may receive 100,000 contacts from input cells. Overall the human brain may contain between 1014 and 1015 synaptic connections. The diverse chemical substances that carry information between neurons are called neurotransmitters. Otto Loewi discovered the first neurotransmitter in 1926 when he demonstrated that acetylcholine carried a chemical signal from the vagus nerve to the heart that slowed the cardiac rhythm. Since that time, more than one hundred substances and a far larger number of receptors have been implicated in synaptic transmission (Box 1). Because of the remarkably diverse effects of neurotransmitter-mediated signaling at the receptor and postreceptor levels, the number of neurotransmitters, as large as it is, vastly understates the complexity of signaling in the brain. In the nervous systems of higher animals, only a small fraction of neurons are directly involved in transducing sensory information or controlling output cells, such as endocrine, smooth muscle or striated muscle cells. The vast majority form what Nauta [2] called the great intermediate net, which underlies the extraordinary computational power of the brain. The complex set of neuronal networks interposed between input and output neurons form the basis, inter alia, for learning complex motor sequences, for thought, emotion, for ‘top down’ behavioral control and, in humans, for such functions as language, writing poetry and planning wars. In addition to performing present-oriented computations, the nervous system is plastic; it alters itself (forms memories) as it processes information, so that it can respond more adaptively in the future. The subtlety and complexity of the brain’s outputs, along with its ability to change in response to new information, is supported by a rich set of mechanisms for cell–cell communication involving at an anatomical level, intricate but plastic local connections, larger scale neural circuits and overlying global regulatory systems; and at the chemical level, a large number of neurotransmitters with highly diverse mechanisms for decoding their informational content. Because neurotransmitters play such a central role in brain function, neurotransmitter receptors and other proteins involved in neurotransmitter synthesis and inactivation are critical targets for the development of therapeutic drugs meant to treat psychiatric and neurologic disorders, pain, and a host of other ills [3]. Moreover, natural substances, such as cocaine, opiates, nicotine, ethyl alcohol and LSD, that can mimic or interfere with actions of neurotransmitters, exert potent effects on human behavior [3]. Neurons are specialized to receive, process, and transmit information (Figure 1). As a first approximation, information is represented electrically within neurons and chemically (by neurotransmitters) between neurons. Once released, neurotransmitters diffuse across the synapse to bind to postsynaptic receptors. It should Monoamines and acetylcholine Acetylcholine Dopamine Norepinephrine Epinephrine Serotonin Histamine