Growth Factor Regulation of Neuromodulatory Circuits

Neuromodulatory circuits, including dopaminergic, noradrenergic, serotonergic, cholinergic, and histaminergic systems, exert widespread influence over brain function, shaping cognition, emotion, motivation, learning, reward, and behavior. The proper development, maintenance, and plasticity of these circuits depend on a tightly coordinated array of molecular cues, among which growth factors play a central role. Neurotrophins such as BDNF, NGF, NT-3, and NT-4, along with GDNF family ligands, FGFs, IGFs, and other growth factors, regulate neuronal survival, axonal targeting, synapse formation, dendritic complexity, and activity-dependent plasticity in neuromodulatory neurons and their targets. Dysregulation of these signaling pathways is increasingly recognized as a common feature across neurological and psychiatric disorders, from Parkinson’s disease and Alzheimer’s disease to depression, anxiety, and addiction. Despite substantial progress, key questions remain about how growth factor signaling integrates with neuromodulatory activity across developmental stages, brain regions, and disease contexts, and how this knowledge can be translated into effective therapies.

This Research Topic aims to advance understanding of how growth factors regulate the development, maintenance, plasticity, and repair of neuromodulatory circuits, and how disruptions in these processes contribute to brain disease. We seek studies that dissect the molecular and cellular mechanisms by which neurotrophins and other growth factors influence neuromodulatory neurons and their downstream targets, including effects on synaptic structure and function, circuit connectivity, and activity-dependent plasticity. Contributions exploring the interplay between growth factor signaling and neuromodulator release, receptor dynamics, and behavioral outcomes are particularly welcome. We also encourage work using advanced methodologies such as optogenetics, chemogenetics, in vivo imaging, single-cell transcriptomics, and circuit mapping to link molecular events to circuit-level and behavioral consequences. Translational studies examining growth factor-based therapeutic strategies for neurological and psychiatric disorders, including delivery approaches, biomarker development, and disease-modifying interventions, are strongly encouraged, with the broader goal of bridging fundamental mechanisms and clinical application.

We invite contributions spanning molecular, cellular, circuit, behavioral, and translational research that address growth factor regulation of neuromodulatory circuits. Topics of interest include, but are not limited to:
• Neurotrophin and growth factor signaling in dopaminergic, noradrenergic, serotonergic, cholinergic, and histaminergic systems
• Roles of BDNF, NGF, NT-3, NT-4, GDNF, FGFs, and IGFs in neuromodulatory circuit development
• Growth factor regulation of synapse formation, maturation, and plasticity
• Activity-dependent and experience-dependent growth factor signaling
• Interaction between growth factors and neuromodulator release, receptors, and downstream pathways
• Circuit-level and behavioral consequences of altered growth factor signaling
• Growth factor dysregulation in neurological disorders (e.g., Parkinson’s, Alzheimer’s)
• Growth factor dysregulation in psychiatric disorders (e.g., depression, anxiety, addiction)
• Therapeutic strategies leveraging growth factors, including delivery, gene therapy, and small molecules
• Advanced methodologies (optogenetics, chemogenetics, single-cell omics, in vivo imaging) applied to growth factor-neuromodulator interactions

We encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, reviews and perspectives.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: Neurotrophins (BDNF, NGF, GDNF), Neuromodulatory circuits, Synaptic plasticity, Circuit development and repair, Neurological and psychiatric disorders

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.