Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures
Open accessAbstract
The excitability of cortical circuits is modulated by interneurons that release the inhibitory neurotransmitter GABA. In primate and rodent visual cortex, activity deprivation leads to a decrease in the expression of GABA. This suggests that activity is able to adjust the strength of cortical inhibition, but this has not been demonstrated directly. In addition, the nature of the signal linking activity to GABA expression has not been determined. Activity is known to regulate the expression of the neurotrophin brain-derived neurotrophic factor (BDNF), and BDNF has been shown to influence the phenotype of GABAergic interneurons. We use a culture system from postnatal rat visual cortex to test the hypothesis that activity is regulating the strength of cortical inhibition through the regulation of BDNF. Cultures were double-labeled against GABA and the neuronal marker MAP2, and the percentage of neurons that were GABA-positive was determined. Blocking spontaneous activity in these cultures reversibly decreased the number of GABA-positive neurons without affecting neuronal survival. Voltage-clamp analysis of inhibitory currents demonstrated that activity blockade also decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal neuron firing rates. All of these effects were prevented by incubation with BDNF during activity blockade, but not by neurotrophin 3 or nerve growth factor. Additionally, blockade of neurotrophin signaling mimicked the effects of activity blockade on GABA expression. These data suggest that activity regulates cortical inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an important role in the control of cortical excitability.
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BDNF was the first secreted factor suggested to play a role in homeostatic plasticity.
“BDNF was the first such secreted factor suggested to play a role in homeostatic plasticity (Rutherford et al. 1997(Rutherford et al. , 1998)).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1997
The Discussion (page not specified in our copy) says BDNF regulates inhibition in cortical cultures and may help reduce inhibition when activity falls too low, supporting a role in homeostatic plasticity. The paper does not establish the historical claim that BDNF was the first secreted factor suggested to have that role. (LLM, conf=0.84)
Experimental — accuracy not yet measuredActivity-dependent BDNF release is critical for scaling of inhibitory synapses onto pyramidal neurons and for homeostatic regulation of excitatory synapses onto inhibitory neurons.
“A number of reports have suggested that activity-dependent BDNF release is critical for scaling of inhibitory synapses onto pyramidal neurons as well as the homeostatic regulation of excitatory synapses onto inhibitory neurons (Rutherford et al. 1997(Rutherford et al. , 1998;;Copi et al. 2005;Swanwick et al. 2006).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1997
The Discussion reports that activity blockade reduces inhibition onto cortical pyramidal neurons and that exogenous BDNF prevents this reduction, supporting the inhibitory part of the claim. It infers reduced endogenous BDNF production rather than directly demonstrating activity-dependent release, and it does not establish homeostatic regulation of excitatory synapses onto inhibitory neurons; the excitatory currents it mentions are onto pyramidal neurons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBDNF is known to induce maturation of PV+ interneurons.
“which is activated by brain derived neurotrophic factor (BDNF), which itself is known to induce maturation of PV+ interneurons (Huang et al., 1999; Rutherford et al., 1997).”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Rutherford et al., 1997
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References 40 · Cited by 381
- Authors
- Rutherford, L. C., DeWan, A., Lauer, H. M., & Turrigiano, G. G.
- Affiliations
- Brandeis University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-06-15
- Volume
- 17
- Issue
- 12
- Pages
- 4527-4535
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573348
- OpenAlex
- W2130464434
- Cited by
- 381
- References
- 40
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 10 · 2015: 13 · 2014: 11 · 2013: 17 · 2012: 12
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9421233)
- Whitehall Foundation
- Amgen
- National Institutes of Health (5k02ns001893-03)
- National Institute of Neurological Disorders and Stroke (K02 NS01893)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, cortical inhibition, GABAergic interneurons, activity-dependent regulation, spontaneous activity, visual cortex, neurotrophin signaling, neurotrophin-3, nerve growth factor, pyramidal neurons, neuronal excitability
- MeSH terms
- Animals, Animals, Newborn, Carbazoles, Cell Survival, Cells, Cultured, gamma-Aminobutyric Acid, Interneurons, Membrane Potentials, Microtubule-Associated Proteins, Nerve Growth Factors, Neurons, Tetrodotoxin, Visual Cortex, Signal Transduction, Receptors, Nerve Growth Factor, Pyramidal Cells, Patch-Clamp Techniques, Brain-Derived Neurotrophic Factor, Neurotrophin 3, Indole Alkaloids, Rats
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