Intrahippocampal injection of Cortistatin-14 impairs recognition memory consolidation in mice through activation of sst2, ghrelin and GABAA/B receptors

Abstract

Cortistatin-14 (CST-14), a neuropeptide related to somatostatin, is primarily localized within the cortex and hippocampus. In the hippocampus, CST-14 inhibits CA1 neuronal pyramidal cell firing and co-exists with GABA. However, its role in cognitive is still not clarified. The first aim of our study was to elucidate the role of CST-14 signaling in consolidation and reconsolidation of recognition memory in mice, using novel object recognition task. The results showed that central CST-14 induced in impairment of long-term and short-term recognition memory, indicating memory consolidation impairment effect. Similarly, we found that CST-14 did not impaired long-term and short-term reconsolidation recognition memory. To further investigate the underlying mechanisms of CST-14 in memory process, we used cyclosomatostatin (c-SOM, a selective sst1–5 receptor antagonist), cyanamid154806 (a selective sst2 receptor antagonist), ODN-8 (a high affinity and selectivity compound for sst3 receptor), [d-Lys3]GHRP-6 (a selective ghrelin receptor antagonist), picrotoxin (PTX, a GABAA receptor antagonist), and sacolfen (a GABAB receptor antagonist) to research its effects in recognition. Our results firstly indicated that the memory-impairing effects of CST-14 were significantly reversed by c-SOM, cyanamid154806, [d-Lys3]GHRP-6, PTX and sacolfen, but not ODN-8, suggesting that the blockage of recognition memory consolidation induced by CST-14 involves sst2, ghrelin and GABA system. The present study provides a potential strategy to regulate memory processes, providing new evidence that reconsolidation is not a simple reiteration of consolidation.