BDNF Has Opposite Effects on the Quantal Amplitude of Pyramidal Neuron and Interneuron Excitatory Synapses
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Recently, we have identified a novel form of synaptic plasticity that acts to stabilize neocortical firing rates by scaling the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of neuronal activity. Here, we show that the effects of activity blockade on quantal amplitude are mediated through the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the effects of activity blockade on pyramidal quantal amplitude. BDNF had opposite effects on pyramidal neuron and interneuron quantal amplitudes and modified the ratio of pyramidal neuron to interneuron firing rates. These data demonstrate a novel role for BDNF in the homeostatic regulation of excitatory synaptic strengths and in the maintenance of the balance of cortical excitation and inhibition.
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BDNF, Arc, TNFa, MHC1, b3 integrins, PICK1, and scaffold proteins PSD-95 and PSD-93 can all contribute to, or are essential for, synaptic scaling in dissociated cultures.
“Additionally, there is evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) (Rutherford et al. 1998), the immediate early gene Arc (Shepherd et al. 2006), the cytokine TNFa (Stellwagen and Malenka 2006;Steinmetz and Turrigiano, 2010), the immune molecule MHC1 (Goddard et al. 2007), b3 integrins (Cingolani et al. 2008), the AMPAR binding protein PICK1 (Anggono et al. 2011), and”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
In neocortical networks, the net effects of changes in excitation and inhibition appear homeostatic.
“Although in neocortical networks the net effects of changes in excitation and inhibition appear to be homeostatic (Rutherford et al. 1998;Turrigiano et al. 1998;Maffei et al. 2004), different classes of inhibitory synapse are regulated differently by lowered activity.”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
Activity-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. 1998
In neocortical neurons, activity-dependent BDNF release could mediate synaptic scaling.
“Blocking BDNF signaling mimics, and exogenous BDNF application prevents, the effects of activity blockade on excitatory minis, suggesting that in neocortical neurons activitydependent BDNF release could mediate synaptic scaling (Rutherford et al. 1998).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
In dissociated cortical cultures, excitatory synapses onto excitatory pyramidal neurons are scaled up by activity blockade, whereas excitatory synapses onto GABAergic interneurons are not.
“In dissociated cortical cultures it has been shown that excitatory synapses onto excitatory pyramidal neurons are scaled up by activity blockade, whereas excitatory synapses onto GA-BAergic interneurons are not (Rutherford et al. 1998).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
Blocking BDNF signaling mimics the effects of activity blockade on excitatory minis, and exogenous BDNF application prevents them.
“Blocking BDNF signaling mimics, and exogenous BDNF application prevents, the effects of activity blockade on excitatory minis, suggesting that in neocortical neurons activitydependent BDNF release could mediate synaptic scaling (Rutherford et al. 1998).”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
Enhancing network activity increases excitatory transmission onto GABAergic interneurons.
“On the other hand, enhancing network activity does increase excitatory transmission onto GABAergic interneurons (Rutherford et al. 1998;Chang et al. 2010), which should promote the recruitment of additional inhibition when activity in a circuit increases.”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Rutherford et al. 1998
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. 1998
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- Authors
- Rutherford, L. C., Nelson, S. B., & Turrigiano, G. G.
- Affiliations
- Brandeis University (US)
- Corresponding author
- Turrigiano, Gina G
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 21
- Issue
- 3
- Pages
- 521-530
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1971156703
- Cited by
- 451
- References
- 5
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 14 · 2016: 22 · 2015: 15 · 2014: 20 · 2013: 27 · 2012: 22
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02ns001893-03)
- Genentech
- National Institute of Neurological Disorders and Stroke (K02 NS01893, R01NS036853)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- brain-derived neurotrophic factor, pyramidal neurons, interneurons, synaptic plasticity, homeostatic synaptic scaling, TrkB receptor
- MeSH terms
- Animals, Cells, Cultured, gamma-Aminobutyric Acid, Gene Expression Regulation, Humans, Immunoglobulin G, Interneurons, Models, Neurological, Quantum Theory, Recombinant Fusion Proteins, Recombinant Proteins, Synapses, Tetrodotoxin, Visual Cortex, Receptors, Nerve Growth Factor, Pyramidal Cells, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Brain-Derived Neurotrophic Factor, Excitatory Postsynaptic Potentials, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Rats
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