Neuromodulation of Circuits with Variable Parameters: Single Neurons and Small Circuits Reveal Principles of State-Dependent and Robust Neuromodulation
Open accessAbstract
Neuromodulation underlies many behavioral states and has been extensively studied in small circuits. This has allowed the systematic exploration of how neuromodulatory substances and the neurons that release them can influence circuit function. The physiological state of a network and its level of activity can have profound effects on how the modulators act, a phenomenon known as state dependence. We provide insights from experiments and computational work that show how state dependence can arise and the consequences it can have for cellular and circuit function. These observations pose a general unsolved question that is relevant to all nervous systems: How is robust modulation achieved in spite of animal-to-animal variability and degenerate, nonlinear mechanisms for the production of neuronal and network activity?
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Neuromodulators such as dopamine, acetylcholine, and norepinephrine fundamentally reconfigure circuit properties, qualitatively changing input-output functions, intrinsic excitability, and even the direction of plasticity.
“However, neuromodulators like dopamine, acetylcholine, and norepinephrine fundamentally reconfigure circuit properties—not merely adjusting weights but qualitatively changing input–output functions, intrinsic excitability, and even the direction of plasticity (Dayan 2012; Marder et al. 2014).”
From The myth of the Bayesian brain (2025) · cites this paper as Marder et al. 2014
The “Modulation of Single Neurons and Synapses” section says modulators alter synaptic strength and intrinsic membrane-channel properties, and “Degenerate Neuromodulatory Actions” describes dopamine inducing bursting in a previously silent neuron. These passages support substantial changes in excitability and circuit behavior, but our copy does not establish that dopamine, acetylcholine, and norepinephrine each change input–output functions or the direction of plasticity (no page numbers were supplied). (LLM, conf=0.86)
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References 99 · Cited by 262
- Authors
- Marder, E., O'Leary, T., & Shruti, S.
- Affiliations
- Brandeis University (US)
- Volen Center and Biology Department, Brandeis University, Waltham, Massachusetts 02454;, ,
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2014-07-08
- Volume
- 37
- Issue
- 1
- Pages
- 329-346
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- OpenAlex
- W2107325419
- Cited by
- 262
- References
- 99
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 16 · 2023: 17 · 2022: 17 · 2021: 21 · 2020: 23 · 2019: 28 · 2018: 32 · 2017: 22 · 2016: 30 · 2015: 21 · 2014: 6
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- Funders
- Charles A. King Trust
- National Institutes of Health (MH 46742)
- National Institute of Mental Health (MH 46742)
- National Institute of Neurological Disorders and Stroke (R37NS017813, NS17813)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- neuromodulation, state dependence, single neurons, network activity, nonlinear modulation
- MeSH terms
- Animals, Behavior, Animal, Homeostasis, Models, Neurological, Neural Pathways, Neurons, Synapses, Neurotransmitter Agents, Connectome
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