The retrosplenial cortex (RSC) has been shown to be involved in a number of cognitive functions, in particular episodic memory and navigation, but relatively little is known about responses at the neuronal level. We have analysed activity in the RSC of awake mice to simple visual stimuli using two-photon calcium imaging and found that single cells respond in a coarse spatially but not orientation selective manner. Interestingly, activity was strongly modulated by the animals’ locomotion, even in complete darkness. We further investigated the pattern of activity in RSC as mice were trained on a spatial memory task and found evidence for the formation of a memory engram. The stability of this engram was linked to the animals’ performance upon re-exposure to the task.