About this Research Topic
Goal: The overarching goal of this research topic is to provide a state-of-the-art and unifying view of the mechanisms by which neuromodulators such as acetylcholine (ACh), noradrenaline (NA), serotonin (5-HT), dopamine (DA) and histamine (HA) regulate the genetic, cellular, synaptic and microcircuit levels of brain function.
An important objective of this research topic is to allow a wide range of submissions and enable a comprehensive coverage of the field. Therefore, in order to be broadly inclusive of all relevant ideas and concepts the submission deadline to this research topic is open-ended. The topic editors will accept submissions until an optimal number of articles is reached.
Motivation: Every cognitive function of the mammalian brain is regulated by neuromodulatory systems. Consequently, decades of research have attempted to understand the anatomy, physiology and pharmacology of neuromodulatory systems. Distinct groups of neurons located in subcortical areas release neuromodulators such as ACh, NA, 5-HT, DA, and HA. These neuromodulators directly control information processing in neuronal microcircuits modulating shifts between activity states such as sleep and wakefulness, or distraction and attention. Neuromodulators are directly implicated in a spectrum of debilitating disorders such as migraine, schizophrenia, Alzheimer’s and Parkinson’s disease. Yet, despite their crucial role in physiology and pathology, we lack a systematic understanding of the way they regulate the emergent states of the brain.
Numerous studies have offered insight into the structure, function, receptor composition, and interactions of neuromodulatory systems and suggested some of their possible roles in cognition, behavior, and brain diseases. However, most of these studies have yielded disparate data – from different brain regions in animals belonging to different species, strains, ages, and genders, under different experimental conditions, which makes their reconciliation rather complicated. Therefore, in order to obtain a fundamental understanding of the differential effects of major neuromodulators on specific brain regions, it is crucial to first understand neuromodulatory function at the level of a local microcircuit in a single brain region – the smallest functional unit containing a near complete set of neuromodulatory targets, for example the neocortical microcircuit, or the hippocampal CA1 region.
Expected outcomes: This Research Topic aims to rekindle the field of neuromodulation and, by exposing key open questions, aims to enable a new research path that could lead to a unifying systems-level understanding of how neuromodulatory systems control brain states. It is expected that contributions to this Research Topic will enable an encyclopedic state-of-the-art view and far reaching insights on the major neuromodulators – ACh, NA, 5-HT, DA, and HA – and their actions on gene expression, protein translation, neurons and glia, dendrites, synapses, emergent states in microcircuits and the whole brain. The outcomes could, therefore, provide a strong basis for a quantitative assessment of the regulation of neuronal microcircuits by major neuromodulators, and lead to a better understanding of their role in brain health and disease.
Keywords: neural circuits, brain states, acetylcholine, noradrenaline, serotonin, dopamine, histamine