Hippocampal SSTR4 somatostatin receptors control the selection of memory strategies.

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.