The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Interneuron activity controls endocannabinoid-mediated presynaptic plasticity through calcineurin
Open accessAbstract
Retrograde signaling by endocannabinoids (eCBs) mediates a widely expressed form of long-term depression at excitatory and inhibitory synapses (eCB-LTD), involving a reduction in neurotransmitter release. In the hippocampus, eCB-LTD occurs at interneuron (IN)-pyramidal cell (PC) synapses (I-LTD), and its induction requires a presynaptic reduction of cAMP/PKA signaling resulting from minutes of type 1 cannabinoid receptor (CB1R) activation. Although repetitive activity of glutamatergic synapses initiates the eCB mobilization required for I-LTD, it is unclear whether CB1R-containing GABAergic terminals are passive targets of eCBs or whether they actively contribute to induction. Here, we show that the minutes-long induction period for I-LTD may serve as a window to integrate associated spontaneous activity in the same IN receiving the retrograde eCB signal. Indeed, reducing spontaneous IN firing blocked I-LTD, which could be rescued with extra stimulation of inhibitory afferents. Moreover, cell pair recordings showed that a single IN expressed LTD onto a PC only if it was active during eCB signaling. Several methods of disrupting presynaptic Ca(2+) dynamics all blocked I-LTD, strongly suggesting that IN spikes regulate I-LTD by raising Ca(2+) at the nerve terminal. Finally, inhibiting the Ca(2+)-activated phosphatase, calcineurin, fully blocked I-LTD, but blocking another phosphatase did not. Our findings support a model where both CB1R signaling and IN activity shift the balance of kinase and phosphatase activity in the presynaptic terminal to induce I-LTD.
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“In addition, CB1R negatively regulates N- and P/Q-type voltage-gated calcium channels [26] and positively regulates inwardly rectifying K+ channels [26,27], as well as protein serine/threonine phosphatase 2B (calcineurin, PP2B) to change the phosphorylation state of various effector molecules [28,29].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [29]
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Cites
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Role of Endogenous Cannabinoids in Synaptic Signaling
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Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses
Wilson, R. I., & Nicoll, R. A. (2001) · Nature · doi:10.1038/35069076 · Cited by 1,607
A second endogenous cannabinoid that modulates long-term potentiation
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Spike Timing-Dependent Plasticity of Neural Circuits
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ENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
Chevaleyre, V., Takahashi, K. A., & Castillo, P. E. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112834 · Cited by 829
Self-citationPostsynaptic endocannabinoid release is critical to long-term depression in the striatum
Gerdeman, G. L., Ronesi, J. A., & Lovinger, D. M. (2002) · Nature Neuroscience · doi:10.1038/nn832 · Cited by 795
An Essential Role for Protein Phosphatases in Hippocampal Long-Term Depression
Mulkey, R. M., Herron, C. E., & Malenka, R. C. (1993) · Science · doi:10.1126/science.8394601 · Cited by 699
Heterosynaptic LTD of Hippocampal GABAergic Synapses
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Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,595
Endocannabinoid Signaling and Synaptic Function
Castillo, P. E., Younts, T. J., Chávez, A. E., & Hashimotodani, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.020 · Cited by 1,191
Self-citationEndocannabinoid signaling as a synaptic circuit breaker in neurological disease
Katona, I., & Freund, T. F. (2008) · Nature Medicine · doi:10.1038/nm.f.1869 · Cited by 579
Endocannabinoid Signaling and Long-Term Synaptic Plasticity
Heifets, B. D., & Castillo, P. E. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163149 · Cited by 516
Self-citationAstrocyte signaling controls spike timing–dependent depression at neocortical synapses
Min, R., & Nevian, T. (2012) · Nature Neuroscience · doi:10.1038/nn.3075 · Cited by 361
Metadata
- Authors
- Heifets, B. D., Chevaleyre, V., & Castillo, P. E.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-07-22
- Volume
- 105
- Issue
- 29
- Pages
- 10250-10255
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2481322
- OpenAlex
- W2040301525
- Cited by
- 116
- References
- 47
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 6
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- presynaptic plasticity, calcineurin, CB1 receptor, hippocampus, cAMP/PKA signaling, phosphatase activity
- MeSH terms
- Animals, Electric Stimulation, Electrophysiology, Hippocampus, Interneurons, Neuronal Plasticity, Tetrodotoxin, Signal Transduction, Rats, Sprague-Dawley, Pyramidal Cells, Patch-Clamp Techniques, Calcineurin, Calcium Signaling, Long-Term Synaptic Depression, Receptor, Cannabinoid, CB1, Rats, Cannabinoid Receptor Modulators, Endocannabinoids, Calcineurin Inhibitors, In Vitro Techniques
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