Using Molecular Biology to Address Locus Coeruleus Modulation of Hippocampal Plasticity and Learning: Progress and Pitfalls

Abstract In investigating locus coeruleus (LC) modulation of hippocampal plasticity and learning, newer methodologies offer significant advantages over older approaches. We describe our experience with Arc cat FISH methodology and optogenetic activation of LC. We also offer suggestions for troubleshooting those techniques. The Arc cat FISH approach makes it possible to index network effects of LC activation. Our experience indicates that temporal patterns of LC firing, and bilaterality of LC activation, are critical for specific functional outcomes. Optogenetics offers the possibility of manipulating temporal patterns of LC firing, which our Arc cat FISH network studies suggest will be critical for understanding its role in behavior. Our experience with rat LC demonstrates that monitoring cell responses in vivo during light activation is required for interpreting functional outcomes. We suggest further that optogenetics offers a tool for exploring the modularity of LC in the larger nucleus of the rat.