Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala
Open accessAbstract
Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2 decreases both glutamatergic and GABAergic synaptic transmission via activation of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of neuronal excitability. This suggests that the effects on excitatory transmission override those on inhibitory transmission. Here we show that CB1 activation by WIN55,212-2 and Delta(9)-THC inhibits long-term depression (LTD) of basal synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900 pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G(i/o) proteins, activation of inwardly rectifying K+ channels (K(ir)s), inhibition of the adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of voltage-gated N-type Ca2+ channels (N-type VGCCs). Interestingly, WIN55,212-2 effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional mutants lacking CB1 expression only in GABAergic interneurons, but were still present in mutants lacking CB1 in principal forebrain neurons. LTD induction per se was unaffected by the CB1 antagonist SR141716A and was normally expressed in CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the LA. These findings suggest that CB1 expressed on either glutamatergic or GABAergic neurons play a differential role in the control of synaptic transmission and plasticity.
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Stimulation of CB1R recruits various signaling pathways, including Gi/o coupling that reduces adenylyl cyclase and downregulates cAMP/PKA signaling, Gβγ-induced PLC-β-mediated calcium influx, and activation of MAP kinases.
“Stimulation of CB1R recruits various signaling pathways [22]. These pathways include CB1R coupling to Gi/o proteins that reduces adenylyl cyclase activity and downregulates cyclic AMP/protein kinase A signaling [23], by Gβγ-induced phospholipase C-β-mediated increases in intracellular calcium influx, and by activation of mitogen-activated protein kinases [24,25].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [23]
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References 45 · Cited by 68
Research works printed but not linked: 2
- Herkenham, M. 1995. Localization of cannabinoid receptors in brain and periphery. In Cannabinoid receptors (ed. R.G. Pertwee), pp. 145-166. Academic Press, London.
- Rugg, M.D., Johnson, J.D., Park, H., and Uncapher, M.R. 2008. Encoding-retrieval overlap in human episodic memory: A functional neuroimaging perspective. In Progress in brain research, 169 (eds. W. Sossin et al.), Section IV. Elsevier, Amsterdam.
- Authors
- Azad, S. C., Kurz, J., Marsicano, G., Lutz, B., Zieglgänsberger, W., & Rammes, G.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Inserm (FR)
- Johannes Gutenberg University Mainz (DE)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-03
- Volume
- 15
- Issue
- 3
- Pages
- 143-152
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC2275656
- OpenAlex
- W2111103317
- Cited by
- 68
- References
- 45
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 391)
- Topics
- Health Sciences › Medicine › Pharmacology › 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
- CB1 receptor, GABAergic interneurons, lateral amygdala, long-term depression, WIN 55,212-2, Δ9-THC, inwardly rectifying potassium channels, protein kinase A, N-type calcium channels, synaptic plasticity, CB1 knockout mice, neuronal excitability
- MeSH terms
- Amygdala, Animals, Calcium Channel Blockers, gamma-Aminobutyric Acid, Interneurons, Mice, Inbred C57BL, Morpholines, Naphthalenes, Neuronal Plasticity, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, GTP-Binding Protein alpha Subunits, Gi-Go, Excitatory Postsynaptic Potentials, Calcium Channels, N-Type, Potassium Channels, Voltage-Gated, Long-Term Synaptic Depression, Receptor, Cannabinoid, CB1, Benzoxazines, Mice
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