Abstract
The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca2+ and the activation of specific 2-AG synthesizing (i.e., DAGLα) enzymes. However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca2+-binding proteins (CaBPs) is still unknown. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. CB1, DAGLα, and MAGL labeling was mainly localized in fibers and neuropil, which were differentially organized depending on the hippocampal CaBPs-expressing cells. CB+1 fiber terminals localized in all hippocampal principal cell layers were tightly attached to calbindin+ cells (granular and pyramidal neurons), and calretinin+ and parvalbumin+ interneurons. DAGLα neuropil labeling was selectively found surrounding calbindin+ principal cells in the dentate gyrus and CA1, and in the calretinin+ and parvalbumin+ interneurons in the pyramidal cell layers of the CA1/3 fields. MAGL+ terminals were only observed around CA1 calbindin+ pyramidal cells, CA1/3 calretinin+ interneurons and CA3 parvalbumin+ interneurons localized in the pyramidal cell layers. Interestingly, calbindin+ pyramidal cells expressed FAAH specifically in the CA1 field. The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions.
Highlights
Reviewed by: Ricardo Insausti, University of Castilla-la Mancha, Spain Pedro Grandes, Basque Country University, Spain Floris G
We performed Western blot analysis to ensure that CB1 receptor, DAGLα, MAGL, fatty acid amide hydrolase (FAAH), calbindin, calretinin, and parvalbumin antibodies recognize the corresponding antigens in the rat hippocampus (Figure 1B)
The role of the endocannabinoid 2-AG on the retrograde suppression of excitatory/inhibitory synaptic transmission requires both release from membrane precursors by the Ca2+-dependent DAGLα and the activation of CB1 receptors that modulate Ca2+-dependent mechanisms such as the inhibition of neurotransmitter release (D’Amico et al, 2004; Di et al, 2005; Katona and Freund, 2008)
Summary
Reviewed by: Ricardo Insausti, University of Castilla-la Mancha, Spain Pedro Grandes, Basque Country University, Spain Floris G. The anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca2+-binding proteins (CaBPs) is still unknown For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. INTRODUCTION ns-2-arachidonoylglycerol (2-AG), one of the endogenous ligands for cannabinoid receptors, regulates synaptic transmission in the nervous system by acting as a retrograde inhibitory signal of excitatory/inhibitory synapses (Katona and Freund, 2008; Stella, 2009, see Figure 1A for summary). Effective production of 2-AG from diacylglycerol (DAG) is demonstrated by combined weak mGluR1-PLC β1/4 cascade activation and Ca2+ elevation to a submicromolar range (Maejima et al, 2001, 2005; Hashimotodani et al, 2005; Ohno-Shosaku et al, 2005)
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