Retinal Modulation of Basal Forebrain Circuits - PROJECT SUMMARY Light is a ubiquitous feature of the natural environment and plays a central role in modulating an organism’s internal state. This flexible adaptation of neural circuits is essential for an organism’s survival. It endows them with not only the ability to preemptively adapt neural circuits to rhythmic, predictable changes in light levels, but also to reactively adapt circuits to acute, unpredictable changes in light levels. Decades of research have established a neural circuit through which light flexibly modulates internal state based on daily rhythms in light. However, the mechanism through which light acutely tunes internal state is currently unknown. This proposal aims to identify a mechanism through which light can acutely influence a wide range of neural circuits. Retinal ganglion cells are the output cells of the retina and send information to over 50 areas in the brain. Among these regions which receive direct retinal input is the basal forebrain. The basal forebrain houses the acetylcholine neuromodulatory system, which sends information throughout the brain to acutely influence a wide range of behaviors. The basal forebrain is known to modulate numerous behaviors including attention, arousal, sleep/wake, and learning and memory. Notably, all these behaviors are also modulated by light. Thus, the retinal input to the basal forebrain is a strong candidate for the acute modulation of behavior based on environmental light. This proposal will identify the types of visual information which are relayed to the basal forebrain, the basal forebrain circuits and cell types this information is integrated into, and how this contributes to light modulation of behavior. In Aim 1, I will identify the retinal inputs to the basal forebrain and define the neural circuits this visual information is integrated into using virus-mediated circuit tracing and electrophysiology. In Aim 2, I will determine how retinal input to the basal forebrain influences a basal forebrain dependent behavior. Collectively, the proposed experiments will identify retinal inputs to one of the key neuromodulatory centers in the brain, providing insight into the mechanism through which light can acutely modulate a wide range of behaviors.
