Monoamines and the orchestration of behavior.(Articles)

Animals possess a Hch repertoire of behaviors, each generated by the orchestrated activity of assemblies of neurons. Neuromodulators, and particularly monoamines, have been found to play a role in the recruitment of such assemblies. The role of specific monoamines in the modulation of be havior has been particularly well studied using invertebrate animals as models. In these animals, the neuronal assemblies underlying a behavior often consist of fewer neurons than those in vertebrates, and in many cases the activity of specific neurons can be causally linked to the expression of a specific behavior. In this overview, we illustrate the concept of chemical orchestration of behavior, using well-studied models of how monoamines modulate complex and long-lasting behaviors in invertebrate animals.

Keywords: behavior, monoamines, invertebrates, neuroethology, neuromodulation

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All animal behavior is the outcome of the orchestrated activity of large assemblies of neurons in the central nervous system. Within such an assembly, each neuron can be recruited by chemical compounds known as neurotransmitters, neuromodulators, and neurohormones. Neurotransmitter molecules are released into the synapse, where they act directly on receptor channels in the cell membrane and produce rapid opening of these channels for brief periods, at a time scale of milliseconds. This induces a rapid change in the electrical activity of neurons. Neuromodulators are released into a broader area than are neurotransmitters, but they are nevertheless targeted. Like neurotransmitters, neuromodulators bind to receptors in the cell membrane, but these receptors are generally linked to G proteins that activate intracellular signaling cascades, with effects on the electrical activity of neurons lasting seconds, minutes, hours, days, or even weeks. Neuromodulators have a wide variety of effects at the molecular level, including (a) modulation of ion channels and receptors and (b) changes in protein synthesis, enzyme activity, and gene transcription. Unlike the other two categories of neuroactive substances, neurohormones are circulated in the blood or hemolymph and thus act globally within the organism.

The monoamines are neuromodulators derived from single amino acids (figure 1). The major representatives of the monoamines that are known to modulate well-defined behaviors are dopamine, noradrenaline, octopamine, and serotonin. The amino acid tyrosine is converted to dopamine, noradrenaline, or octopamine, whereas serotonin derives from tryptophan. Monoamines and their synaptic receptor targets are classes of molecules with highly conserved roles in synaptic transmission in all animals (Walker et al. 1996). In the vertebrate brain, monoamines mediate a variety of central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation (Kandel et al. 2000). Dysfunctions ha monoamine neurotransmission, particularly of dopamine and serotonin, are implicated in many neurologic and neuropsychiatric disorders, including Parkinson's disease and schizophrenia (Kobayashi 2001), and drugs that are effective in treating these disorders act primarily on monoaminergic systems.

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The idea of chemical coding of specific behaviors was born out of experiments showing that local application of certain neuromodulators in the central nervous system can reproducibly evoke a single coherent bebavior. This idea was elaborated by Graham Hoyle when he and his research associates discovered that injection of the neuromodulator octopamine in the thoracic portion of a locust's central nervous system released flight-like behavior (Sombati and Hoyle 1984). Hoyle formulated the "orchestration hypothesis" which stipulates that the release of specific neuromodulators activates specific central neuronal circuits un derlying specific behaviors (Hoyle 1985), and he certainly merits credit for stimulating an era of intensive research based on his idea. Subsequently, other neuromodulators, particularly the monoamines, have been found to release well-defined behaviors (Bicker and Menzel 1989).

In vertebrates, the neuromodulation by monoamines of large assemblies of neurons is difficult to study, owing to the complexity of the vertebrate central nervous system and the large number of neurons involved in the orchestration of a given behavior. Thus, how and where monoamines act in the brain to modulate behavior is still poorly understood. Invertebrates, on the other hand, provide good models to study this modulation, for the following reasons: (a) The behavior of interest is often exhibited by a restrained animal whose nervous system has been exposed for electrophysiological manipulations; (b) the behavior under investigation is often generated by a relatively small number of neurons, and each neuron is often large enough to permit intracellular recording, stimulation, and staining in the behaving animal; and (c) stimulation of single neurons can occasionally produce an unambiguous behavioral response in the restrained animal. Admittedly, experimental attempts to show such a direct causal relationship have not always been successful, even in invertebrate animals. This is most likely because, even in these animals, it is assemblies of neurons, rather than single neurons, that are responsible for initiation or modulation of behavior. Nevertheless, with the combination of advantages mentioned above, invertebrate animals provide models that give researchers the opportunity to define the neuronal circuits underlying a behavior and also the cellular mechanisms that initiate it.

Our goal in this overview is to illustrate the concept of chemical orchestration of behavior using two well-studied examples of monoamine-induced complex bebaviors in invertebrate animals. With these examples, we will explain the design of experiments whose aim is to establish the causal relationship between a monoamine, the neurons that synthesize the monoamine,…