PROBING CORTICAL PLASTICITY AND PREFRONTAL COUPLING WITH AN MTL-DEPENDENT MICROSTIMULATION PARADIGM

Memory consolidation relies on activity-dependent neuronal plasticity, with long-range inputs from medial temporal lobe (MTL) structures playing a crucial role in associative learning. In the neocortex, these inputs predominantly target layer 1 (L1), yet how they specifically alter local microcircuits to support information storage remains largely unknown. Here, we employ an MTL-dependent cortical microstimulation paradigm in which mice learn to associate intracortical direct current stimulation of primary somatosensory cortex (S1) with a water reward. Simultaneous Neuropixels recordings provide high-resolution electrophysiological data from all cortical layers, allowing us to track dynamic changes in activity before, during, and after learning. By applying advanced quantitative analyses, we aim to identify how each cortical layer adapts its response within the behavioral timescale and how these changes reflect the formation of new associative memories. In S1, most neurons across layers showed increased firing and burst activity after learning, while only a small subset decreased their activity. The overall distribution of firing patterns remained consistent, indicating that distinct neuronal populations did not emerge between naïve and expert animals. Layer-specific adaptations in S1 were further linked to coordinated activity within medial and lateral prefrontal cortex (mPFC and lPFC), revealing large-scale interactions between sensory and frontal regions during memory formation. Together, these findings highlight how associative learning reshapes local and distributed cortical dynamics, advancing our understanding of the mechanisms by which memory traces are formed and consolidated.