How environment and experience alter hippocampal CA2 function – BadBoredom

While the ability to form and recall memories is essential for survival, it is also key to forming relationships with others and defines our sense of self. The hippocampus has long been recognized as a fundamental structure for learning and memory formation. The focus of this project is on area CA2, a hippocampal region that is essential for social memory and hippocampal network activity. This region shows unique and marked vulnerability in numerous psychiatric and neurodegenerative diseases. Thus, a better understanding of CA2 PN function will have important consequences not only for understanding memory processes, but also for early disease detection and treatment.

It is well-established that environmental enrichment through novel experience and active engagement with surroundings improves brain function and plays a key role in determining the onset and severity of neurological diseases. Using an animal model of the 22q11.2 deletion syndrome, we have found that these animals only have cognitive impairments and problems in CA2 physiology in standard caging conditions. These results indicate that CA2 PNs have a singular vulnerability to a poor environment. Furthermore, we also see environmentally induced changes in the cellular properties of CA2 PNs in wild-type animals that are likely responsible for the amelioration in the disease model. From our data, we know that there are long-term changes in CA2 PN properties that occur over 3 weeks as well as rapid changes in CA2 PN plasticity that take place in a matter of hours. In this project, we plan to explore these phenomena by answering the following questions: 1) What are the molecular mechanisms underlying the changes in CA2 PN intrinsic properties in mice that have spent three weeks in an enriched environment? 2) What signaling pathways allow CA2 PNs to undergo synaptic plasticity following novelty exposure?