Figure 3.
Circadian circuitry underlying behavioral aggression and the PRAM pathway. A midsaggital section of a mouse brain illustrating loci involved in circadian modulation of aggressive behavior and PRAM-associated arousal and affective behavior. Light input to the retina activates the SCN, which in turn inhibits the SPZ. Since the SPZ is primarily inhibitory, SCN activation disinhibits downstream targets of the SPZ such as the ventromedial hypothalamus (VMH), leading to aggression. Disruption of this pathway in people with AD and dementia may result in aggressive behavioral symptoms such as sundowning. Similarly, light input to the retina activates the SCN, in turn activating the DMH, possibly via disinhibition of SPZGABA neurons. Increased DMH activity stimulates the LC, increasing arousal and modulating affect. Activating this pathway carries potential as a possible therapeutic strategy for treating disorders of arousal and mood.