GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression
Open accessAbstract
Tetanus-induced heterosynaptic depression in the hippocampus is a key cellular mechanism in neural networks implicated in learning and memory. A growing body of evidence indicates that glial cells are important modulators of synaptic functions, but very little is known about their role in heterosynaptic plasticity. We examined the role of glial cells in heterosynaptic depression, knowing that tetanization and NMDA application caused depression of synaptic field responses (fEPSPs) and induced Ca 2+ rise in glial cells. Here we report that chelating Ca 2+ in a glial syncytium interfered with heterosynaptic depression and NMDA-induced fEPSP depression, suggesting that Ca 2+ activation of glial cells is necessary for heterosynaptic depression. The NMDA-induced Ca 2+ rise in glial cells was sensitive to tetrodotoxin and reduced by the GABA B antagonist CGP55845 . Both heterosynaptic depression and simultaneous Ca 2+ activation of glial cells were prevented by CGP55845 , suggesting an involvement of the GABAergic network in glial activation and heterosynaptic depression. Also, the GABA B agonist baclofen caused both a Ca 2+ rise in glial cells and fEPSP depression. Heterosynaptic depression, as well as NMDA- and baclofen-induced depression, were attenuated by an A 1 antagonist, cyclopentyl-theophylline, whereas glial cell activation was not, indicating a role of adenosine downstream of glial activation. Finally, heterosynaptic depression requires ATP degradation because ectonucleotidase inhibitors reduced this plasticity. Our work indicates that Ca 2+ activation of glial cells is necessary for heterosynaptic depression, which involves the sequential interaction of Schaffer collaterals, the GABAergic network, and glia. Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses.
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Adenosine signaling through presynaptic A1 receptors lowers the release probability of glutamate-containing vesicles.
“Adenosine signaling through adenosine A1 (A1A) receptors at the presynaptic membrane leads to a reduced release probability of glutamate-containing vesicles”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [96]
This adenosine signaling reduces glutamatergic transmission.
“and thus reduced glutamatergic transmission [96]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [96]
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“Adenosine signaling through adenosine A1 (A1A) receptors at the presynaptic membrane leads to a reduced release probability of glutamate-containing vesicles and thus reduced glutamatergic transmission [96] (Figure 5).”
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- Authors
- Serrano, A., Haddjeri, N., Lacaille, J.-C., & Robitaille, R.
- Affiliations
- Université de Montréal (CA)
- Lyon 1 Université (FR)
- Corresponding author
- Robitaille, Richard
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-05-17
- Volume
- 26
- Issue
- 20
- Pages
- 5370-5382
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6675310
- OpenAlex
- W1978111097
- Cited by
- 398
- References
- 41
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 13 · 2022: 19 · 2021: 18 · 2020: 19 · 2019: 22 · 2018: 18 · 2017: 18 · 2016: 18 · 2015: 22 · 2014: 31 · 2013: 19 · 2012: 33
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- heterosynaptic depression, glial cells, hippocampus, GABAB receptors, baclofen, adenosine A1 receptor, ectonucleotidases, ATP degradation, Schaffer collaterals, synaptic plasticity, neuron-glia interactions
- MeSH terms
- Animals, Calcium, Electric Stimulation, gamma-Aminobutyric Acid, Hippocampus, Male, Nerve Net, Neural Inhibition, Neural Pathways, Synaptic Transmission, Neuroglia, Organ Culture Techniques, Receptors, GABA-A, Rats, Sprague-Dawley, Receptors, GABA-B, Excitatory Amino Acid Agonists, GABA Agonists, GABA Antagonists, Excitatory Postsynaptic Potentials, Calcium Signaling, Long-Term Synaptic Depression, Receptor, Adenosine A1, Rats, GABA-A Receptor Agonists, GABA-B Receptor Agonists, GABA-A Receptor Antagonists, GABA-B Receptor Antagonists, Adenosine A1 Receptor Antagonists
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