CHEMOGENETIC MANIPULATION OF MEMORIES IN MICE

According to the standard model of Memory Consolidation, memories are initially encoded through hippocampal (HC) and neocortical (NC) activity patterns and subsequently consolidated during slow-wave sleep (SWS). Complementary Learning Systems Theory (CLST) proposes that new memories are rapidly acquired by the hippocampus and gradually integrated into distributed neocortical networks, reducing interference with previously stored information¹.
To investigate these principles, we developed a novel virtual reality (VR) based memory task that enables assessment of recent and remote memory retrieval in mice. This framework allows a controlled examination of the time-dependent contribution of the hippocampus to memory expression.
Previous work suggests that the hippocampus plays a role in recent memory retrieval, whereas remote memories may progressively rely on neocortical circuits through consolidation and corticalization processes². Transient manipulation of hippocampal activity, therefore, provides a powerful strategy to probe how memories of different ages depend on distinct neural substrates.
In this study, we used chemogenetic inhibition of the hippocampus via Designer Receptors Exclusively Activated by Designer Drugs (DREADD) hM4Di³, to reversibly manipulate neural activity and assess the effects of hippocampal inactivation on recent and remote memory in a VR.
This experimental framework enables testing key predictions of systems consolidation and CLST models while investigating chemogenetic tools to dissect the causal role of the hippocampus in memory retrieval across time.
1. McClelland et al., 1995; 2.Frankland & Bontempi, 2005; 3.Roth, 2016