Experience-Dependent Plasticity to Visual Sequences in Mouse Anterior Cingulate Cortex Reflects Familiarity

Anterior cingulate cortex (ACC) is a prefrontal area implicated in functions including cognitive control, attention, and prediction. Mouse ACC receives input from the visual system and uses visual information to direct behavior. While extensive work has described experience-dependent plasticity in mouse V1, less is known about how ACC itself adapts to visual experience. Our previous work demonstrated that visual sequences, presented across days, can drive plasticity in the timing of visually evoked responses in mouse ACC. However, it is not known whether this plasticity ("sequence plasticity") reflects familiarity to the first stimulus in a sequence or expectation of subsequent stimuli-a distinction that is critically important for understanding its functional significance. We recorded visually evoked responses in awake, head-fixed female and male mice trained with visual sequences across days. Visual sequences drove plasticity in ACC, expressed through a change in response timing, that reflects familiarity to the first stimulus. In addition, experience-dependent plasticity could be induced using single-orientation stimuli. Together, these findings suggest that "sequence plasticity" in ACC does not in fact require sequences, but rather reflects a broader phenomenon that we term stimulus-specific response plasticity in timing (SRPT). Our prior work demonstrated that ACC plasticity is impaired in a mouse model of Angelman syndrome (AS). Here, AS model mice showed abnormal responses to familiar visual stimuli in ACC, despite normal plasticity in V1. Together, this work demonstrates how mouse ACC adapts to familiar visual stimuli and describes impaired ACC function in a mouse model of a neurodevelopmental disorder.