Beyond the wiring diagram: signalling through complex neuromodulator networks

Abstract

During the computations performed by the nervous system, its 'wiring diagram'-the map of its neurons and synaptic connections-is dynamically modified and supplemented by multiple actions of neuromodulators that can be so complex that they can be thought of as constituting a biochemical network that combines with the neuronal network to perform the computation. Thus, the neuronal wiring diagram alone is not sufficient to specify, and permit us to understand, the computation that underlies behaviour. Here I review how such modulatory networks operate, the problems that their existence poses for the experimental study and conceptual understanding of the computations performed by the nervous system, and how these problems may perhaps be solved and the computations understood by considering the structural and functional 'logic' of the modulatory networks.

Distinct or shared actions of peptide family isoforms: I. Peptide-specific actions of pyrokinins in the lobster cardiac neuromuscular system

“…For example, the numerically simple systems of decapod crustaceans have been instrumental in refining our understanding of how the actions of individual and unique combinations of neuromodulators, including peptides, are capable of reconfiguring 'hard-wired' neural networks to allow for an almost infinite array of distinct behavioral outputs (e.g. Brezina, 2010;Briggman and Kristan, 2008;Christie et al, 2010a;Dickinson, 2006;Rauscent et al, 2006;Stein, 2009). …”

Gastric and pyloric motor pattern control by a modulatory projection neuron in the intact crabCancer pagurus

“…Thus modulatory projection neurons such as MCN1 can control the motor output in vivo, and they participate in the processing of exteroceptive sensory information in behaviorally relevant conditions. stomatogastric nervous system; central pattern generator; sensorimotor; descending control; neuromodulation ONE OF THE BIGGEST CHALLENGES today is to determine how the neuromodulatory system contributes to the neuronal plasticity that allows the nervous system to respond adequately to different behavioral tasks (Gu 2002;Calabrese 2003;Krichmar 2008;Brezina 2010). In particular, motor pattern generating circuits show a high degree of flexibility due to neuromodulatory substances that trigger new patterns or modify ongoing activity (Morgan et al 2002;Nusbaum and Beenhakker 2002;Marder et al 2005;Dickinson 2006;Sakurai and Katz 2009).…”

Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales

“…Contractile properties are also commonly non-linear, and can have distinct dynamics relative to motor neuron spike timing (Brezina et al, 2000;Enoka and Fuglevand, 2001;Hooper and Weaver, 2000;JorgeRivera et al, 1998). Further, from presynaptic transmitter release to the regulation of contraction machinery, all aspects of the neuromuscular transform are subject to neuromodulation and thus can differ according to the behavioral state of the organism (Brezina, 2010;Brezina et al, 2000;Hooper and Weaver, 2000;Williams et al, 2013;Worden, 1998). Given the prevalence of neuromodulators acting on muscles, including in the STNS (Brezina, 2010;Fort et al, 2004;Hooper et al, 1999;Jorge-Rivera and Marder, 1996;Jorge-Rivera et al, 1998;Wali, 1985;Weimann et al, 1997;Worden, 1998;Wu and Cooper, 2012), it is possible that there are modulatory conditions in which the balance of depression and facilitation, and the properties of augmentation between the three muscles may converge.…”

“…Further, from presynaptic transmitter release to the regulation of contraction machinery, all aspects of the neuromuscular transform are subject to neuromodulation and thus can differ according to the behavioral state of the organism (Brezina, 2010;Brezina et al, 2000;Hooper and Weaver, 2000;Williams et al, 2013;Worden, 1998). Given the prevalence of neuromodulators acting on muscles, including in the STNS (Brezina, 2010;Fort et al, 2004;Hooper et al, 1999;Jorge-Rivera and Marder, 1996;Jorge-Rivera et al, 1998;Wali, 1985;Weimann et al, 1997;Worden, 1998;Wu and Cooper, 2012), it is possible that there are modulatory conditions in which the balance of depression and facilitation, and the properties of augmentation between the three muscles may converge. Similarly, relaxation kinetics are modulated, and the differences in summation between the three muscles could converge under a particular modulatory environment (Jing et al, 2010;Jorge-Rivera et al, 1998).…”