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Hippocampal SSTR4 somatostatin receptors control the selection of memory strategies

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Abstract

Rationale

Somatostatin (SS14) has been implicated in various cognitive disorders, and converging evidence from animal studies suggests that SS14 neurons differentially regulate hippocampal- and striatal-dependent memory formation. Four SS14 receptor subtypes (SSTR1–4) are expressed in the hippocampus, but their respective roles in memory processes remain to be determined.

Objectives

In the present study, effects of selective SSTR1–4 agonists on memory formation were assessed in a water-maze task which can engage either hippocampus-dependent “place” and/or striatum-dependent “cue” memory formation.

Materials and methods

Mice received an intrahippocampal injection of one of each of the selective agonists and were then trained to locate an escape platform based on either distal cues (place memory) or a visible proximal cue (cue memory). Retention was tested 24 h later on probe trials aimed at identifying which memory strategy was preferentially retained.

Results

Both SS14 and the SSTR4 agonist (L-803,087) dramatically impaired place memory formation in a dose-dependent manner, whereas SSTR1 (L-797,591), SSTR2 (L-779,976), or SSTR3 (L-796,778) agonists did not yield any behavioral effects. However, unlike SS14, the SSTR4 agonist also dose-dependently enhanced cue-based memory formation. This effect was confirmed in another striatal-dependent memory task, the bar-pressing task, where L-803,087 improved memory of the instrumental response, whereas SS14 was once again ineffective.

Conclusions

These data suggest that hippocampal SSTR4 are selectively involved in the selection of memory strategies by switching from the use of hippocampus-based multiple associations to the use of simple dorsal striatum-based behavioral responses. Possible neural mechanisms and functional implications are discussed.

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Acknowledgement

The authors thank Merck and Co, Inc. (NJ, USA) for generously providing the SSTRs selective agonists and Dr. Tom Durkin for helpful comments on the manuscript. This study was supported by the CNRS, the INSERM, and the Conseil Régional d’Aquitaine. FG and GL hold fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche.

Conflict of interest

All listed authors have contributed significantly to the manuscript and consent to their names on the manuscript. The authors declare that there is no possible conflict of interest in the conduct and reporting of this research.

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Authors and Affiliations

  1. Université de Bordeaux, Centre de Neurosciences Intégratives et Cognitives, Université de Bordeaux 1, Avenue des facultés, 33405, Talence, France

    François Gastambide & Jean-Louis Guillou

  2. CNRS UMR 5228, Talence, France

    François Gastambide & Jean-Louis Guillou

  3. Université Paris Descartes, Faculté de médecine, IFR 77 Broca Sainte-Anne, Paris, France

    Cécile Viollet, Gabriel Lepousez & Jacques Epelbaum

  4. Inserm UMR 894, Centre de Psychiatrie et Neurosciences, Bât Paul Broca, 2 ter rue d’Alésia, 75014, Paris, France

    Cécile Viollet, Gabriel Lepousez & Jacques Epelbaum

  5. Hôpital Saint Anne, Centre Paul Broca, 2 ter Rue Alésia, 75014, Paris, France

    Cécile Viollet, Gabriel Lepousez & Jacques Epelbaum

Authors
  1. François Gastambide
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  2. Cécile Viollet
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  3. Gabriel Lepousez
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  4. Jacques Epelbaum
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  5. Jean-Louis Guillou
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Correspondence to Jean-Louis Guillou.

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Gastambide, F., Viollet, C., Lepousez, G. et al. Hippocampal SSTR4 somatostatin receptors control the selection of memory strategies. Psychopharmacology 202, 153–163 (2009). https://doi.org/10.1007/s00213-008-1204-x

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  • DOI: https://doi.org/10.1007/s00213-008-1204-x

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