Synaptic and network plasticity

Why study hippocampal area CA2? This relatively small yet under-studied region in the hippocampus receives powerful excitatory sensory information from the cortex and dentate gyrus. Unlike areas CA1 and CA3, CA2 receives input from hypothalamic regions that are very active during emotional and social context, resulting in the release of neuromodulators such as vasopressin and oxytocin that are known to effect learning and social interaction. Furthermore, the pyramidal neurons and interneurons of area CA2 have unique circuitry, physiology and molecular make-up that sets this region apart from other hippocampal areas.

Our goal is to better understand how area CA2 is incorporated into the hippocampal circuit and under which circumstances this region is most active. Our team currently has a cutting-edge set of tools that allows us to examine the circuitry and physiology of the interneurons and pyramidal cells in area CA2 and the hypothalamus in adult mice. We routinely use electrophysiology, optogenetics and pharmacogenetics to selectively excite or silence CA2 pyramidal neurons.  With these methods, our team has discovered unique plasticities of inhibitory transmission that occurs in area CA2 (Piskorowski and Chevaleyre, 2013; Loisy et al, Neuron 2022).

Area CA2 shows marked vulnerability in multiple psychiatric disorders (Knable, Mol Psychiatry 2004). Reports from human post-mortem studies as well as research performed by our team have discovered that both interneurons and pyramidal cells undergo profound age-dependent changes in area CA2 (Piskorowski et al, Neuron, 2016). Thus, a better understanding of area CA2 can have profound consequences not only for understanding learning and memory, but also for the understanding of psychiatric disease. Because of the unique molecular identity of neurons in area CA2, this region holds particular promise for the development of potential pharmacological treatments for the symptoms in numerous psychological disorders.