Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice

Somatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. However, the specific role of this somatostatin receptor subtype in these regions is largely undetermined. In this study, we investigated the role of the sst2 receptor in the hippocampus using mice invalidated for the sst2 gene (sst2 KO mice). Complementary experimental approaches were used. First, mice were tested in behavioral tests to explore the consequences of the gene deletion on learning and memory. Spatial discrimination learning in the radial maze was facilitated in sst2 KO mice, while operant learning of a bar-pressing task was slightly altered. Mice were then processed for electrophysiological study using the ex vivo hippocampal slice preparation. Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning.