A matter of focus: monoaminergic modulation of stimulus coding in mammalian sensory networks

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Although the presence of neuromodulators in mammalian sensory systems has been noted for some time, a groundswell of evidence has now begun to document the scope of these regulatory mechanisms in several sensory systems, highlighting the importance of neuromodulation in shaping feature extraction at all levels of neural processing. The emergence of more sophisticated models of sensory encoding and of the interaction between sensory and regulatory regions of the brain will challenge sensory neurobiologists to further incorporate a concept of sensory network function that is contingent on neuromodulatory and behavioral state.

Introduction

For sensory systems to guide behavior in adaptive ways, they must focus selectively on stimuli that are most likely to influence survival and reproduction. Coding and filtering of sensory signals are accomplished by the tuning of sensory receptors and by circuitry that uses classical neurotransmitters in ascending or descending pathways. Much evidence suggests that several intrinsic neuromodulatory systems further impose dynamic filters, whose properties are tied to environmental events or internal state, upon sensory circuits. Just as occurs in motor systems, endogenous neuromodulators transform sensory circuits into pluripotent networks, whose outputs can be fine-tuned to fit ever-changing behavioral circumstances.

A chemically diverse array of neuromodulators affect sensory circuit function. Here we limit our focus to two brainstem monoaminergic pathways and their respective neuromodulatory transmitters — norepinephrine (NE) and serotonin (5-hydroxytryptamine or 5-HT) — in the mature mammalian brain. Although other neuromodulatory substances have been shown to alter sensory processing, we focus on NE and 5HT because a great deal is known regarding the sources, effects on sensory processing, and mechanisms of action of these two molecules. In addition, aspects of the role of another important signalling molecule within sensory systems, acetylcholine, have recently been reviewed [1]. In mammals, both NE and 5-HT are synthesized and released by clusters of brainstem neurons that project broadly throughout cortical and subcortical sensory structures 2., 3.. Although there have been many studies on the operation of NE and 5-HT in specific mammalian sensory systems, there has been less analysis of whether unifying principles of the neuromodulatory actions of these agents apply across systems.

Here, we address this issue by asking three fundamental questions. First, do these neuromodulators exert comparable effects on feature detection in different sensory pathways? Second, are the mechanisms underlying their neuromodulatory actions similar for different sensory modalities? Third, are there common principles of action by which these neuromodulatory systems regulate sensory-dependent behaviors? Overall, we find support in the literature for substantial similarities in the general ways in which NE and 5-HT function across diverse sensory networks.

Section snippets

NE, 5-HT and feature detection

The predominance of data suggests that, with several exceptions, NE and 5-HT do not transmit detailed information regarding sensory stimuli but rather alter the responses of sensory circuits to sensory-driven inputs 4., 5.. In recent years, however, it has also become increasingly clear that NE and 5-HT do not simply regulate overall levels of activity in sensory pathways, but instead actively shape the response properties of sensory networks.

The transformative nature of the effects of NE and

Mechanisms underlying NE and 5-HT effects

Many of the effects of NE and 5-HT on feature extraction by sensory circuits arise through a nested array of mechanisms that are evident at both the cellular and the circuit level of organization (Figure 2). These are the same mechanisms that have been so well documented in reconfiguring the outputs of motor and other brain circuits 41., 42., 43., 44.•. Within a given sensory circuit, several different mechanisms may interact to influence signal processing.

First, neurons within a circuit may

Impact of neuromodulatory systems on behavior and perception

A converging range of studies suggests that noradrenergic projections from locus coeruleus and serotonergic projections from raphe nuclei regulate signal processing in sensory circuits according to behavioral state. Anatomical studies have shown that both NE and 5-HT projections arise from relatively few neurons that provide input via extensive axonal collateralization to several sensory neuronal circuits throughout the neuraxis 2., 22., 44.•, 56., 57., 58., 59.. The increased discharge of

Conclusions

In light of the complexity and specificity of the effects of NE and 5-HT across sensory circuits, rather than formulate a blanket hypothesis for neuromodulator function in sensory systems, we prefer to summarize this review in terms that may spur inquiry. A unifying principle of the actions of NE and 5-HT in sensory networks is that they are much more nuanced and selective than a simple gain control mechanism would be. Indeed, these agents both modulate specific receptive field properties of

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The authors would like to thank T Cleland, P Telgkamp, and T Smith for helpful comments on the manuscript.

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