A stable sensory map emerges from neurons with unstable tuning properties

Primary sensory cortices are functionally organized according to topographic principles, such as the tonotopic map of auditory cortex. Recently, chronic recordings of neuronal activity have revealed that single cell stimulus tuning can undergo continuous remodeling, which appears to be in conflict with the stability of sensory maps. Using longitudinal two-photon imaging in the auditory cortex of 12 mice (21.506 neurons), we attempt to reconcile the conflicting observations of unstable single-cell tuning properties and stable population-level topographic maps. Using intrinsic imaging and chronic two-photon calcium imaging, we assess tuning properties to pure tones (PT) and more naturalistic, complex sounds (CS). We find that responses to complex sounds, but also topographically organized pure tones are highly volatile and many neurons gain and lose responsiveness regularly over time. We modeled the transitions between four different states of responsiveness (unresponsive, CS-responsive, PT-responsive, CS&PT-responsive) as a discrete-time Markov chain. This simple Markov chain was able to capture the dynamics of responsiveness over a 9-day period, indicating that the turnover is predominantly stochastic and memoryless. The structure of the tonotopic map is nevertheless upheld throughout the experiment by shifting subpopulations of neurons. Assessing the model’s long-term predictions, we found that within 100 days the vast majority of neurons would become responsive to the set of sounds used in our study, at least transiently. This provides an interesting twist on the common observation that it is difficult to evoke a sensory response in a neuron: It may not have been the wrong stimulus, but the wrong day.