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.

Association areas in neocortex encode novel stimulus-outcome relationships, but the principles of their engagement during task learning remain elusive. Using chronic wide-field calcium imaging, we reveal two phases of spatiotemporal refinement of layer 2/3 cortical activity in mice learning whisker-based texture discrimination in the dark. Even before mice reach learning threshold, association cortex-including rostro-lateral (RL), posteromedial (PM), and retrosplenial dorsal (RD) areas-is generally suppressed early during trials (between auditory start cue and whisker-texture touch). As learning proceeds, a spatiotemporal activation sequence builds up, spreading from auditory areas to RL immediately before texture touch (whereas PM and RD remain suppressed) and continuing into barrel cortex, which eventually efficiently discriminates between textures. Additional correlation analysis substantiates this diverging learning-related refinement within association cortex.Our results indicate that a pre-learning phase of general suppression in association cortex precedes a learning-related phase of task-specific signal flow enhancement.

The neuronal mechanisms underlying perceptual grouping of discrete, similarly oriented elements are not well understood. To investigate this, we measured neural population responses using voltage-sensitive dye imaging in V1 of monkeys trained on a contour-detection task. By mapping the contour and background elements onto V1, we could study their neural processing. Population response early in time showed activation patches corresponding to the contour/background individual elements. However, late increased activity in the contour elements, along with suppressed activity in the background elements, enabled us to visualize in single trials a salient continuous contour "popping out" from a suppressed background. This modulated activity in the contour and in background extended beyond the cortical representation of individual contour or background elements. Finally, the late modulation was correlated with behavioral performance of contour saliency and the monkeys' perceptual report. Thus, opposing responses in the contour and background may underlie perceptual grouping in V1.

In neocortex, each sensory modality engages distinct primary and secondary areas that route information further to association areas. Where signal flow may converge for maintaining information in short-term memory and how behavior may influence signal routing remain open questions. Using wide-field calcium imaging, we compared cortexwide neuronal activity in layer 2/3 for mice trained in auditory and whisker-based tactile discrimination tasks with delayed response. In both tasks, mice were either active or passive during stimulus presentation, engaging in body movements or sitting quietly. Irrespective of behavioral strategy, auditory and tactile stimulation activated spatially segregated subdivisions of posterior parietal cortex (areas A and RL, respectively). In the subsequent delay period, in contrast, behavioral strategy rather than sensory modality determined where short-term memory was located: frontomedially in active trials and posterolaterally in passive trials. Our results suggest behavior-dependent routing of sensory-driven cortical information flow from modality-specific PPC subdivisions to higher association areas..