Chemical neurotransmission

Chemical neurotransmission is the way in which neurons communicate by releasing chemical substances that are received by the receptors in the next neuron (or the target) and excite or inhibit it. About 50% or more of dtug mechanisms are based on modification of chemical neurotransmission. 

Cheese Reaction Chemical Chaperone Chemical Library Chemical Neurotransmission Chemoattractant Receptors Chemokine Receptors Chemokines... 

The concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

Over 100 years ago, a debate was raging between the two most famous neuroscientists in the world concerning the nature of the nervous system. Golgi believed that all neurons were connected in a nerve net or syncytium whereas Ramon y Cajal believed that neurons were separated from each other by tiny spaces called synapses. Cajal proved to be correct, and it was later learned that neurons communicate across the synapse by releasing chemical substances known as neurotransmitters or by releasing electrical charges. Because chemical neurotransmission is much more common than electrical transmission, especially in the brain, and it is chemical neurotransmission that is modulated by psychiatric medicines, our discussion will focus on the chemotransmitter process. In simplest terms, the process of chemical neurotransmission occurs in three steps neurotransmitter production, neurotransmitter release, and neurotransmitter action on specific receptors. 

By now, you know that the nervous system is a communications network that serves to control your body. You also know that nerve impulses are the vehicle that carries information around this network. In addition, you know that chemical neurotransmission is the means by which these signals are passed from one neuron to another. Finally, you know that neurotransmitters, receptors, and enzymes are the key components that make all of these things happen. 

When we talk about what a psychiatric medication does, we are invariably discussing its effect on neurotransmission between nerve cells across the synapse. Psychiatric medications act by modulating chemical neurotransmission in the synapse. However, as you probably know, it often takes several days or weeks for depression or psychosis to respond to treatment. Clearly, psychiatric medications work. Why, however, is there often a delay before they begin to do so ... 

Figure 1. Schematic diagram of a synaptic junction demonstrating the principle of chemical neurotransmission.

The alterations in neurotransmitter activity which trigger or accompany the onset of natural sleep and distinguish slow wave or non-REM from REM sleep, provide one of the most compelling arguments in favour of chemical neurotransmission being specifically involved in mechanisms of conscious awareness. For an extensive review on neurochemistry and sleep, see Gottes-man (1999). 

This book adds to numerous preceding texts on consciousness the relatively new concept that particular neurotransmitters may be central to the process. As outlined in the Preface, communication between neurons is essential for consciousness and such communication, on the timescale applicable to conscious perception, is principally mediated by chemical neurotransmission. As Susan Greenfield (2000) points out in The Private Life of the Brain , acetylcholine may enable a whole population of cells to become more important than individual units, a kind of neuroscientific Marxism If the concept of transmitter NCC is incorporated into future discussions of the neurobiology of consciousness, or adds a further dimension to the neuropharmacology of disorders of the brain which affect conscious awareness, this book will have more than served its purpose. 

The best understood chemical neurotransmission occurs at synapses, specialized sites that connect two neurons. Neurons are organized so that they can both send synaptic... 

Chemical neurotransmission can be described in three dimensions space, time and function. 

FIGURE 1 — 3. The synapse is enlarged conceptually here showing its specialized structures that enable chemical neurotransmission to occur. Specifically, a presynaptic neuron sends its axon terminal to form a synapse with a postsynaptic neuron. Energy for this process is provided by mitochondria in the presynaptic neuron. Chemical neurotransmitter is stored in small vesicles ready for release on firing of the presynaptic neuron. The synaptic cleft is the connection between the presynaptic neuron and the postsynaptic neuron. Receptors are present on both sides of this cleft and are key elements of chemical neurotransmission. 

Neurons send electrical impulses from one part of the cell to another part of the same cell via their axons, but these electrical impulses do not jump directly to other neurons. Neurons communicate by one neuron hurling a chemical messenger, or neurotransmitter, at the receptors of a second neuron. This happens frequently, but not exclusively, at the sites of synaptic connections between them (Fig. 1 — 3). Communication between neurons is therefore chemical, not electrical. That is, an electrical impulse in the first neuron is converted to a chemical signal at the synapse between it and a second neuron, in a process known as chemical neurotransmission. This occurs predominantly in one direction, from the presynaptic axon terminal, to any of a variety of sites on a second postsynaptic neuron. However, it is increasingly apparent that the postsynaptic neuron can also talk back to the presynaptic neuron with chemical messengers of its own, perhaps such as the neurotransmitter nitric oxide. The frequency and extent of such cross-communication may determine how... 

The third dimension of chemical neurotransmission is function, namely that cascade of molecular and cellular events set into action by the chemical signaling process. First come the presynaptic and then the postsynaptic events. An electrical impulse in the first, or presynaptic, neuron is converted into a chemical signal at the synapse by a process known as excitation-secretion coupling. 

Thus, the function of chemical neurotransmission is not so much to have a pre-synaptic neurotransmitter communicate with its postsynaptic receptors as to have a presynaptic genome converse with a postsynaptic genome DNA to DNA presynaptic command center to postsynaptic command center. 

Thus, a brief puff of chemical neurotransmission from a presynaptic neuron can trigger a profound postsynaptic reaction, which takes hours to days to develop and can last days to weeks or even longer. Every conceivable component of this entire process of chemical neurotransmission is a candidate for modification by drugs. Most psychotropic drugs act on the processes that control chemical neurotransmission at the level of the neurotransmitters themselves or of their enzymes and especially their receptors. Future psychotropic drugs will undoubtedly act directly on the biochemical cascades, particularly on those elements that control the expression of pre- and postsynaptic genes. Also, mental and neurological illnesses are known or suspected to affect these same aspects of chemical neurotransmission. 

Each neuron was originally thought to use one neurotransmitter only and to use it at all of its synapses. Today, we now know, however, that many neurons have more than one neurotransmitter (Table 1—2). Thus, the concept of co-transmission has arisen. This often involves a monoamine coupled with a neuropeptide. Under some conditions, the monoamine is released alone under other conditions, both are released, adding to the repertoire of options for chemical neurotransmission by neurons that contain both neurotransmitters. 

The reader should now appreciate that chemical neurotransmission is the foundation of psychopharmacology. It has three dimensions, namely, space, time, and function. The spatial dimension is both that of hard wiring as the anatomically addressed nervous system and that of a chemical soup as the chemically addressed nervous system. The time dimension reveals that neurotransmission can be fast (milliseconds) or slow (up to several seconds) in onset, depending on the neurotransmitter or neuromodulator, of which there are dozens. Neurotransmission can also cause actions... 

In Chapter 1 we discussed how modern psychopharmacology is essentially the study of chemical neurotransmission. In this chapter we will become more specific and discuss how virtually all central nervous system (CNS) drugs act in one of two very specific ways on chemical neurotransmission first and most prominently as stimulators (agonists) or blockers (antagonists) of neurotransmitter receptors or second, and less commonly, as inhibitors of regulatory enzymes. 

---