Targeted photostimulation uncovers circuit motifs supporting short-term memory

Short-term memory is associated with persistent neural activity that is maintained by positive feedback between neurons. To explore the neural circuit motifs that produce memory-related persistent activity, we measured coupling between functionally characterized motor cortex neurons in mice performing a memory-guided response task. Targeted two-photon photostimulation of small (<10) groups of neurons produced sparse calcium responses in coupled neurons over approximately 100 μm. Neurons with similar task-related selectivity were preferentially coupled. Photostimulation of different groups of neurons modulated activity in different subpopulations of coupled neurons. Responses of stimulated and coupled neurons persisted for seconds, far outlasting the duration of the photostimuli. Photostimuli produced behavioral biases that were predictable based on the selectivity of the perturbed neuronal population, even though photostimulation preceded the behavioral response by seconds. Our results suggest that memory-related neural circuits contain intercalated, recurrently connected modules, which can independently maintain selective persistent activity.