Several studies in mice have revealed that there are differences in the molecular make-up of and plasticity at CA3–CA1 pyramidal neuron synapses that depend on whether the presynaptic input comes from the left or right CA3. To detect any functional effects of this asymmetry, Shipton et al. assessed the performance of mice in hippocampus-dependent memory tasks while optogenetically silencing their left or right CA3. Silencing the left but not the right CA3 impaired long-term spatial memory, suggesting the existence of functional asymmetry between the left and right CA3 in mice.