Circuit regulation along an activity continuum shapes flexible and stable representations during learning

In medial entorhinal cortex of learning mice, a persistent excitatory activity axis links low-activity neurons to flexible landmark-to-reward encoding and high-activity neurons to stable spatial representations.

• Why it matters: Learning must both adapt representations to new experiences and stabilize them for lasting memory, but how circuits balance these competing demands is unclear.
• What they did: Using longitudinal calcium imaging in mice as they learned novel virtual environments, the study tracked excitatory and interneuron activity and related it to dopaminergic pre-reward ramping and inhibitory interactions.
• The result: Dopaminergic pre-reward ramping coincided with reward encoding emergence in low-activity neurons, while inhibitory interneurons showed opposing activity and transient novelty responses that delayed excitatory remodeling, stabilization, and behavioral learning.

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