The loss of memories is the earliest and often most detrimental symptom in the course of Alzheimer’s disease (AD), the most common form of dementia. The loss of neuronal cells, which are assumed to carry mnemonic information, suggests itself to be the leading cause of memory loss. Besides, the question of alternative mechanisms has been raised. Our lab recently showed that an additional cell ensemble, so-called novelty-like cells, interfered with the engram and thus, impaired memory recall. This suggests a novel mechanism of memory impairment. However, the exact circuit that leads to the evocation of the interfering ensemble in hippocampal CA1 is still not known. A potential candidate circuit involves the actions of somatostatin (SST)-expressing inhibitory interneurons, O-LM interneurons. In this project we will address the role of O-LM interneurons during novel object and context exploration, as well as associative learning. We expect the chemogenetic inactivation of O-LM interneurons during memory formation to cause elevated novelty-associated CA1 activity during memory recall and thus, recall impairment. Conversely, chemogenetic activation of O-LM interneurons may be sufficient to prevent novelty-like activity in CA1 in a mouse model of AD. The analysis of neuronal activity will be performed by examining the immediate early gene cfos at the transcriptional and protein level, using RNA-FISH and immunohistochemistry respectively. Furthermore, we aim at characterizing the novelty-like cell ensemble by combining two-photon in vivo imaging data and transcriptional analysis. We hypothesize that the novelty-like ensemble is characterized by a transcriptional profile that allows its identification post mortem.