Modern neuroscience studies have incorporated direct manipulations of neurons in animal models. This has recently been advanced via expression of synthetic molecules to allow for control of activity with light (e.g. optogenetics) o non- endogenous ligands (e.g. DREADDS). These approaches have revolutionized the field and are now been used more broadly. However, the power of these strategies is limited by our ability to direct them to the proper neurons. To date, the vast majority of optogenetic experiments, for example, have relied on targeting sets of neurons based on expression of a specific gene product. This results in experimental manipulations that do not reflect the normal processes in the brain, where neurons rarely fire according to these molecular categories. Recent work has leveraged molecular tools that allow for the capture or labeling of active neurons during behavior. These neurons, sometimes called an ensemble, can then be replayed, or inhibited, during behavior. We propose the nucleus accumbens medium spiny neurons as an excellent context to test and use this strategy. Specifically, we aim to label sets of nucleus accumbens neurons during both appetitive and aversive behavior. Preliminary data suggests that replay of these neurons is sufficient to alter future behavior - that is, we have captured an ensemble that contains positive or negative valance information. The present experiments will also characterize the circuits that mediate the appetitive/aversive ensemble effects. These efforts will connect ensemble collection with specific cells types and neural circuits, effectively enhancing the power of this approach to understanding the neurobiological basis of behavior.
