The primary visual cortex is an excellent model system for investigating how neuronal populations encode information, because of well-documented relationships between stimulus characteristics and neuronal activation patterns. We used two-photon calcium imaging data to relate the performance of different methods for studying population coding (population vectors, template matching, and Bayesian decoding algorithms) to their underlying assumptions. We show that the variability of neuronal responses may hamper the decoding of population activity, and that a normalization to correct for this variability may be of critical importance for correct decoding of population activity. Second, by comparing noise correlations and stimulus tuning we find that these properties have dissociated anatomical correlates, even though noise correlations have been previously hypothesized to reflect common synaptic input. We hypothesize that noise correlations arise from large non-specific increases in spiking activity acting on many weak synapses simultaneously, while neuronal stimulus response properties are dependent on more reliable connections. Finally, this paper provides practical guidelines for further research on population coding and shows that population coding cannot be approximated by a simple summation of inputs, but is heavily influenced by factors such as input reliability and noise correlation structure.
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