Editorial overview: Neuromodulation: Tuning the properties of neurons, networks and behavior

Abstract

Every neural network, and therefore all components of that network, continually needs to be in the proper state for efficient neural processing and appropriate behavioral performance. Throughout the animal kingdom, behavior requires flexibility and flexibility arises from rearranging network configurations, responses, and properties. Neuromodulation is a major contributor to this flexibility. It has a pervasive influence on nervous system function and behavior in all animals (invertebrate and vertebrate). In fact, the extensive influence of neuromodulation and the remarkable number of degrees of freedom it provides to neural systems is one major reason why there remains much to understand not only from the large biological systems (e.g. mammals: mouse to man) but from the small systems (e.g. crustacean stomatogastric system, nematode Caenorhabditis elegans, fruit fly Drosophila melanogaster). The extensive influence of neuromodulation, from individual synapses to large scale neural networks, and its ability to reconfigure systems during normal and abnormal behavior, is on display in this issue of Current Opinion in Neurobiology.Neuromodulatory systems appear to be phylogenetically ancient but interestingly, as Katz and Lillvis highlight, these systems and their G-protein coupled receptors (GPCRs) have evolved/changed considerably more slowly than the behaviors of the animals in which they are expressed. These authors provide evidence supporting the hypothesis that this mismatch between the rate of change in modulatory systems and in behavioral flexibility is resolved at least partly by the faster rate of change associated with the regulatory mechanisms underlying expression of neuromodulatory systems at particular sites. Such a change can, for example, alter where, and to what degree, particular modulatory systems are expressed. The slow change of the modulatory systems themselves suggests that persisting GPCRs provide a basic 'tool box' by which a network can reinvent itself, modifying through the evolutionary process to achieve new and varied tasks.Modulation of neural network activity results largely from modulatory influences on synapses and the intrinsic physiological properties of neurons. With respect to synapses,

IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses

“…By modifying the input–output relationships between neurons, neuromodulators play crucial roles in information processing by the brain: they are thought to underlie changes in arousal, mood, and global animal states1–4, and to contribute to learning and forgetting5,6. Identifying neuromodulatory signaling pathways and understanding their in vivo effects on circuit function are important goals to understand the neural basis for behavior7.…”

Switchable slow cellular conductances determine robustness and tunability of network states

“…Neuronal processing is constantly shaped by fluctuations in population rhythmic activities, each defining distinctive brain states [ 1 – 4 ]. Neuromodulators organize the switch between different brain states [ 5 , 6 ], changing the way networks process neural signals [ 7 , 8 ]. Precise temporal and spatial control of brain states is required for changes associated with movement, attention, perception, motivation, or expectation [ 9 – 18 ].…”

“…Fast acting neurotransmitter pathways allow for the rapid kinetics required for fast network and signal processing states changes [ 17 ]. Rapid control of network states has been reported to affect spatial attention in cortical circuits [ 6 , 7 ], attention and arousal in the thalamus [ 7 , 18 ], and movement initiation in the subthalamic nucleus [ 14 ]. The most studied example is probably the thalamocortical circuitry.…”

“…At every scale, the rhythms are continuously changing under the action of neuromodulators that modulate cellular and synaptic conductances over time. Neuromodulatory systems act at a cellular scale but their broad projections can simultaneously affect large populations [ 6 , 7 , 17 , 27 ]. Global neuromodulators control the switch of brain states [ 16 , 32 – 34 ].…”

Expression and distribution of neuropeptides in the nervous system of the crab Carcinus maenas and their roles in environmental stress

“…Acclimation to different conditions is crucial to an animal's survival, however, the precise mechanism of how this process occurs remains elusive. Increasing evidence suggests that neuropeptides play an important role in stress regulation . Unfortunately, a comprehensive view of the neuropeptides involved in the stress response is lacking and required to understand their functions inside the nervous system.…”