Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex

The location of short-term memory in mammalian neocortex remains elusive. Here we show that distinct neocortical areas maintain short-term memory depending on behavioral strategy. Using wide-field and single-cell calcium imaging, we measured layer 2/3 neuronal activity in mice performing a whisker-based texture discrimination task with delayed response. Mice either deployed an active strategy—engaging their body toward the approaching texture—or passively awaited the touch. Independent of strategy, whisker-related posterior areas encoded choice early after touch. During the delay, in contrast, persistent cortical activity was located medio-frontally in active trials but in a lateral posterior area in passive trials. Perturbing these areas impaired performance for the associated strategy and also provoked strategy switches. Frontally maintained information related to future action, whereas activity in the posterior cortex reflected past stimulus identity. Thus, depending on behavioral strategy, cortical activity is routed differentially to hold information either frontally or posteriorly before converging to similar action. Gilad et al. measure neural activity from large parts of the neocortex while mice are performing a short-term memory task. They find that short-term memory is localized to a frontal or posterior part of the neocortex, depending on the mouse's behavioral strategy.