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Localization of the CB1 type cannabinoid receptor in the rat basolateral amygdala: high concentrations in a subpopulation of cholecystokinin-containing interneurons
Abstract
The neuronal localization of the CB1 cannabinoid receptor in the rat basolateral amygdala was studied using peroxidase and fluorescence immunohistochemical techniques. All nuclei of the basolateral amygdala contained a large number of lightly stained pyramidal neurons and a small number of more intensely stained non-pyramidal neurons. Most of the latter cells had medium-sized to large multipolar somata and three to four aspiny dendrites, but some exhibited smaller oval somata. The axon initial segments of some of these non-pyramidal neurons exhibited large swollen varicosities in colchicine-injected animals, suggesting that much of the CB1 receptor protein is transported down the axons of these cells. Double-labeling studies using immunofluorescence histochemistry combined with confocal laser scanning microscopy revealed that the great majority of non-pyramidal neurons with CB1 receptor immunoreactivity belonged to a cholecystokinin-containing subpopulation. Whereas none of the other subpopulations of non-pyramidal neurons (exhibiting immunoreactivity for calretinin, parvalbumin, or somatostatin) expressed high levels of CB1 receptor immunoreactivity, a small percentage of these cells exhibited low levels of immunoreactivity. The results indicate that cannabinoids may modulate the activity of pyramidal projection neurons as well as a subpopulation of cholecystokinin-containing non-pyramidal neurons in the basolateral amygdala. Previous studies indicate that most of the latter are inhibitory interneurons that utilize GABA as a neurotransmitter. The intense staining of the cholecystokinin-containing interneurons and the evidence that large amounts of CB1 receptor protein are transported down the axons of these cells suggests that, as in the hippocampus, cannabinoids may inhibit the release of GABA from the axon terminals of these neurons.
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“Following their synthesis, ECBs are retrogradely transported into the extracellular space to bind ECB receptors present on presynaptic terminals [19–21].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [21]
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“It has reciprocal connections with the MeA and CeA (Dong et al., 2001a; Shammah-Lagnado et al., 2000) and receives projections from the hippocampus (Dong et al., 2001b), BLA (Dong et al., 2001a) and the mPFC (Vertes, 2006).”
BackgroundInfluentialBehavioral Neurobiology of the Endocannabinoid System
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“…al., 1993, Marsicano and Lutz, 1999, Chhatwal et al., 2005, Hermann and Lutz, 2005), CB1 protein expression is more intense in the lateral subdivision of the CeA (CeAL) than the centromedial amygdala (Kamprath et al., 2011, McDonald and Mascagni, 2001, Ramikie and Patel, 2012, Tsou et al., 1998).”
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“Immunohistochemistry to CB1R was performed similar as previously described (Tsou et al., 1998; McDonald and Mascagni, 2001).”
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“Projections from IL onto the ITCs appear to be important for extinction (Likhtik et al., 2008), but it is not known whether those synapses are modifiable.”
BackgroundInfluentialSucrose-induced plasticity in the basolateral amygdala in a ‘comfort’ feeding paradigm
Packard, A. E. B., Di, S., Egan, A. E., Fourman, S. M., Tasker, J. G., & Ulrich‐Lai, Y. M. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1454-7 · Cited by 17
“…BLA interneuron subtypes: SOM (D-20) (goat polyclonal; 1:250; sc-7819; Santa Cruz Biotechnology, Dallas, TX, USA) (Cox et al. 2008); CCK (mouse monoclonal; 1:1000; ab37274; CCK8; abcam) (McDonald and Mascagni 2001); and PV (mouse monoclonal; 1:1000; P3088, Sigma-Aldrich) (Rainnie et al. 2006).”
Song, C., Kang, X., Yang, F., Du, W., Zhang, J., Liu, L., Kang, J., Jia, N., Yue, H., Fan, L., et al. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0134 · Cited by 15
“In the amygdala, studies in both rats andmice demonstrated that high levels of functional CB1 receptors were expressed in CCK-expressing basket cells while none of the PV+, SST+, or calretinin+ interneurons expressed high levels of CB1 receptors (Marsicano and Lutz 1999; McDonald and Mascagni 2001; Rovira-Esteban et a…”
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“CB1 can- nabinoid receptors are one of the major receptors in the emotional learning and memory and its neural plasticity process (Laviolette and Grace, 2006; Marsicano et al., 2002) and they have high expression in BLA and medial prefrontal cortex (mPFC) (McDonald and Mascagni, 2001).”
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“…may play a role in fear extinction (Gunduz-Cinar et al. 2013, 2016; Marsicano et al. 2002) through activation of CB1 receptors in the basolateral amygdala, a nucleus that regulates outputs of the central amygdala (McDonald and Mascagni 2001; Lafenêtre et al. 2007; Tovote et al. 2015).”
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“Lower levels of CB1R expression have been observed within BLA pyramidal neurons [6, 7, 72 ].”
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“Likewise, using the same antibody, we saw negligible axonal staining in the BNC of the rat [7].”
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“Except for chemo-genetics and optogenetics, CCK-INs can be indirectly modulated by presynaptic cannabinoid 1 (CB1) receptors which are mainly located at the CCK-IN terminals in BLA (Katona et al., 1999; McDonald and Mascagni, 2001; Nyiri et al., 2005).”
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Metadata
- Authors
- McDonald, A. J., & Mascagni, F.
- Affiliations
- University of South Carolina (US)
- Corresponding author
- McDonald, A.J
- ORCID
- McDonald, A.J
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 107
- Issue
- 4
- Pages
- 641-652
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2034121461
- Cited by
- 157
- References
- 51
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 1
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 41301, P30DK041301)
- National Institute of Neurological Disorders and Stroke (NS 38998)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- CB1 receptor, basolateral amygdala, cholecystokinin, interneurons, non-pyramidal neurons, axonal transport, calretinin, parvalbumin, somatostatin
- MeSH terms
- Amygdala, Animals, Antibody Specificity, Cholecystokinin, Fluorescent Antibody Technique, Immunoenzyme Techniques, Interneurons, Male, Receptors, Drug, Rats, Sprague-Dawley, Microscopy, Confocal, Receptors, Cannabinoid, Rats
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