Neuromodulatory Ascending Systems: Their Influence at the Microscopic and Macroscopic Levels

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Background

The communication between neurons within neural circuits relies on neurotransmitters (i.e.glutamate, γ-aminobutyric acid) and neuromodulators (e.g. acetylcholine, dopamine, serotonin, etc.). These chemicals, inside and outside the synapse, shape the time course of neuronal membrane potentials, which in turn affects the issuance of action potentials and the communication between neurons at different levels of brain organization. Neurotransmitters are responsible for interneuronal communication through highly localized synaptic signaling, whereas neuromodulators are sometimes extrasynaptic and more broadly mediate the efficacy of postsynaptic events: for example, changing the impact of one set of neurons on another. Such modulation is known to have important consequences for behavior, as neuromodulators are closely associated with cognitive enhancement and deficits.
The role of neuromodulatory ascending systems, while essential to nervous system function, is significantly more difficult to study than neurotransmission. That is, because the effects of neuromodulators are of slow onset, long duration, and often have effects that are more complex than simple excitation or inhibition. For instance, neuromodulators have a range of effects on the highly nonlinear dynamics of membrane properties and synapses, enabling neurons to be more flexible in their ability to encode different sorts of information (e.g., sensory information) on a variety of time scales. Importantly, the effects of neuromodulators depend critically on specific receptors, their locus inside and outside of synapses, and the intrinsic dynamics of target neurons or circuits with the consequence of directly modulating their internal state, changing their metabolic demands.
Neuromodulators that have identical action at the single-neuron level can impact circuits very differently depending on the expression, density, and distribution of receptors. One of the challenges in this work was to understand the extent to which neuromodulator actions are coordinated across multiple levels of brain function. In other words, how might combinations of neuromodulators impact or reconfigure circuits such that the same brain systems are able to support a wide range of behaviorally relevant outputs?

This Research Topic aims to disseminate recent advances in our understanding of the neural mechanisms that underlie behavior, with the focus on neuromodulator ascending pathways. Understanding the role of neuromodulatory systems not only requires the characterization of the influence of neuromodulators (e.g., acetylcholine) at the single-cell level but also requires knowledge about architecture and functioning of neural networks where it targets.

We welcome original research studies, review articles, opinion articles, and perspectives that focus on the role of neuromodulatory ascending pathway, including, but not limited to:

a) Anatomical aspects of different neuromodulatory ascending pathway
b) Neurodevelopment and synapse formation of these ascending systems
c) Neuromodulator receptors density and distributions across the brain
d) Species differences, e.g. human, rodents, non-human primates
e) Technological advances for the study of neuromodulators influence
f) The role of neuromodulator systems at the local (microcircuit level) versus the role of neuromodulator systems at a long-distance synaptic circuit, also investigating their effects on cortical activity.
g) Brain disorders associated to neuromodulatory ascending systems

Keywords: Neural Circuits, Neurophysiology & Neuroimaging, Animal Research, Clinical Neuroscience, Neuromodulatory Pathways or neuromodulation system

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