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The Hippocampal Endocannabinoid System in Different Memory Phases: Unveiling the CA1 Circuitry

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Cannabinoid Modulation of Emotion, Memory, and Motivation

Abstract

CB1 Cannabinoid receptors are widely expressed throughout the brain, particularly in areas involved in learning and memory, such as the hippocampus. In the CA1 area, they are mainly present at the presynaptic terminals of both GABAergic and glutamatergic neurons. The antagonist/inverse agonist AM251 is a useful pharmacological tool due to its selectivity and ability to tap into the endocannabinoid system (ECS). When infused into the brain, it interferes with the natural functioning of the local pool of endocannabinoids present in each memory phase, and by suppressing the natural course of events, exposes its function in each situation. Anandamide (AEA) was also studied, but results were less consistent. In a large set of experiments spanning several years we have shown that different memory phases are modulated in opposite, complementary ways: AM251 was amnestic (and AEA, facilitatory) when infused into CA1 both after training (consolidation) or after a long reactivation session (extinction), suggesting that ECS modulates positively these phases. On the other hand, AM251 facilitated (and AEA frequently disrupted) memory before test (retrieval) or after a short reactivation session (reconsolidation), suggesting a negative modulatory role. Thus, simmetrically opposed actions are the rule for the ECS in the CA1 area, suggesting both plastic events and complex selective roles taking place under its control, e.g. “switching” between extinction and reconsolidation. Results were interpreted according to known CA1 circuitry and the most probable position of cannabinoid CB1 receptors, pointing to a complex, multifunctional modulatory system that is perfectly consistent with its ubiquity in mammal brains.

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Notes

  1. 1.

    AM251, is an inverse agonist [126–129], however, since it also acts as a competitive antagonist displacing endocannabinoids at CB1 receptors and because it is not possible to discriminate between both effects in vivo [130], we prefer to classify AM251 as some authors already do, calling it an “antagonist/ inverse agonist”.

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Acknowledgements

JAQ and LOA would like to acknowledge the great contribution made, in particular, by Carla Dalmaz and Sidia C. Jacques, and co-authors Jaderson C da Costa (PUCRS), and Victor A. Molina (UNC, Argentina). Other collaborators over the years include Lucas Fürstenau de Oliveira, Clarissa Camboim, Felipe Diehl, Bruna P. Genro, Vanusa B. Lanziotti, Ricardo V. Breda (PUCRS), Michele F. Pedroso (PUCRS) Douglas S. Engelke, Robson Scheffer-Teixeira, Josué Haubrich, and Lindsey F. Cassini. We have also had the valuable assistance of Mariane Castro da Silva, Marco Alexandre S. da Silva, Ney T. Ferreira Jr, Fabrício H. M. do Monte (UFSC), Andréa A. Tavares, Thiago P. Henriques, and Fabrício Pamplona (UFSC), and the professional and kind technical assistance of Ms. Zelma Regina de Almeida. Over the years, this research received the support of grants and fellowships from several national and international, specially: CAPES (MEC), CNPq & FINEP (MCTI), FAPERGS, PROPESQ/UFRGS, PRPID/PUCRS, SECyT & FONCyT (Argentina) and IFS (Sweden).

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  1. Psychobiology and Neurocomputing Lab (LPBNC), Dept. of Biophysics, IB & Neurosciences Graduate Program, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Jorge Alberto Quillfeldt PhD & Lucas de Oliveira Alvares PhD

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  1. Jorge Alberto Quillfeldt PhD
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  2. Lucas de Oliveira Alvares PhD
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Correspondence to Jorge Alberto Quillfeldt PhD .

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Editors and Affiliations

  1. Dept. of Physiology and Pharmacology, Sapienza University, Rome, Italy

    Patrizia Campolongo

  2. Institute of Neuroscience CNR, University of Cagliari, Cagliari, Italy

    Liana Fattore

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Quillfeldt, J., de Oliveira Alvares, L. (2015). The Hippocampal Endocannabinoid System in Different Memory Phases: Unveiling the CA1 Circuitry. In: Campolongo, P., Fattore, L. (eds) Cannabinoid Modulation of Emotion, Memory, and Motivation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2294-9_3

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