Neuromodulation of synaptic transmission and circuit state

Neuromodulators such as acetylcholine, dopamine, serotonin, norepinephrine, endocannabinoids, and an expanding repertoire of neuropeptides continuously reshape the synaptic landscape of the brain. Rather than simply conveying information, they regulate synaptic gain, sculpt release probability, and dynamically reconfigure local microcircuits to meet ongoing behavioural demands. Through these mechanisms, the same anatomical network can flexibly support distinct computations across arousal, attention, and motivational states. Recent technical advances, including genetically encoded sensors (GRAB, dLight, iSeroSnFR, GRABeCB) coupled with photometry, voltage imaging, and large-scale electrophysiology, now allow neuromodulator release and its synaptic consequences to be monitored with unprecedented spatial and temporal resolution. Combined with cell‑type‑specific perturbations and circuit‑level manipulations, these tools are transforming our view of how chemical signaling at the synapse translates into circuit-level cortical state transitions and enabling adaptive behaviour.

This Research Topic aims to bring together cutting-edge work that connects neuromodulatory signaling at individual synapses to the dynamic states of neural circuits and behavior. We seek contributions that examine how classical neuromodulators, endocannabinoids, neuropeptides, and co-released transmitters shape excitatory and inhibitory transmission, short-term and long-term plasticity, dendritic integration, and network synchronization across brain regions. We particularly welcome studies that leverage methodological innovations including next‑generation neuromodulator sensors, optogenetic and chemogenetic strategies, high‑resolution in vivo imaging, and computational modeling to link molecular events at the synapse with circuit-level reconfiguration during defined behavioral or cognitive states, including arousal, attention, learning, sleep, and stress. We also encourage cross‑species comparative work that reveals conserved or divergent principles of neuromodulatory control across rodents, non‑human primates, and humans. In addition, we also encourage work that explores how disruption of neuromodulatory–synaptic coupling contributes to neurological and psychiatric disorders, including neurodegenerative disorders, addiction, depression, and schizophrenia. By integrating findings across molecular, synaptic, circuit, and behavioral scales, this collection seeks to consolidate emerging principles of state-dependent synaptic computation and identify open questions for the next generation of neuromodulation‑focused neuroscience research.

We welcome contributions spanning invertebrate and vertebrate model systems, including rodent, primate, and human preparations, as well as in vitro, ex vivo, and in vivo approaches. Topics of interest include, but are not limited to:
• Presynaptic and postsynaptic actions of neuromodulators
• Metabotropic receptor signaling at the synapse
• Volume versus point-to-point neuromodulatory transmission
• Neuropeptide and co-transmitter release dynamics
• Modulation of inhibitory microcircuits
• State-dependent plasticity rules
• Neuromodulatory control of dendritic computation
• Sex differences and developmental trajectories of neuromodulatory systems
• Computational frameworks linking synaptic modulation to circuit dynamics
• Translational and disease-focused studies where mechanistic insight is central

We encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini 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: neuromodulation, synaptic plasticity, circuit state, neuromodulator sensors, state-dependent computation

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.