Endocannabinoid receptors contribute significantly to multiple forms of long-term depression in the rat dentate gyrus
- Christine J. Fontaine1,
- Erin L. Gräfe1,
- Cristina Pinar1,
- Itziar Bonilla-Del Río2,3,
- Pedro Grandes1,2,3 and
- Brian R. Christie1,4
- 1Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8W 2Y2, Canada
- 2Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, E-48940 Leioa, Spain
- 3Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country UPV/EHU, E-48940 Leioa, Spain
- 4Island Medical Program and Department of Cellular and Physiological Sciences, University of British Columbia, Victoria, British Columbia, USA
- Corresponding author: brain64{at}uvic.ca
Abstract
Cannabinoid receptors are widely expressed throughout the hippocampal formation, but are particularly dense in the dentate gyrus (DG) subregion. We, and others, have shown in mice that cannabinoid type 1 receptors (CB1Rs) are involved in a long-term depression (LTD) that can be induced by prolonged 10 Hz stimulation of the medial perforant path (MPP)-granule cell synaptic input to the DG. Here, we extend this work to examine the involvement of CB1Rs in other common forms of LTD in the hippocampus of juvenile male and female Sprague–Dawley rats (Rattus norvegicus). We found, as in mice, that prolonged 10 Hz stimulation (6000 pulses) could reliably induce a form of LTD that was dependent upon CB1R activation. In addition, we also discovered a role for both CB1R and mGluR proteins in LTD induced with 1 Hz low-frequency stimulation (1 Hz-LTD; 900 pulses) and in LTD induced by bath application of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG; DHPG-LTD). This study elucidates an essential role for endocannabinoid receptors in a number of forms of LTD in the rat DG, and identifies a novel role for CB1Rs as potential therapeutic targets for conditions that involve impaired LTD in the DG.
Footnotes
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.050666.119.
- Received May 25, 2020.
- Accepted July 2, 2020.
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