Retrosplenial cortex enables context-dependent goal-directed sensorimotor transformation

The ability to dynamically adjust a behavioral response to a stimulus depending on context is of critical importance for animals. To investigate the neural basis supporting context-dependent sensory processing we developed a behavioral task in which mice changed their response to a single whisker deflection according to a continuously present contextual cue. Through unbiased optogenetic inactivation mapping, we found that neuronal activity in sensory and motor cortices contributed to task execution and, interestingly, we uncovered an unexpected role of retrosplenial cortex for contextual integration. Widefield calcium imaging revealed that retrosplenial cortex was the first cortical area to show context discrimination in response to the whisker stimulus, followed by whisker motor cortex. Finally, we combined optogenetic inactivation with calcium imaging to define causal context-dependent changes in sensorimotor processing. Our cortex-wide mapping experiments thus begin to define key cortical nodes for context-dependent sensorimotor transformation and highlight an important contribution of retrosplenial cortex.