Decoding and encoding (de)mixed population responses

•Linear dimensionality reduction methods provide neat summaries of population responses.•Demixing methods additionally demix responses relative to experimental parameters.•Smooth mappings of experimental parameters onto flat neural manifolds boost demixability.•Neural networks with low-rank connectivities can produce demixed manifolds. A central tenet of neuroscience is that the brain works through large populations of interacting neurons. With recent advances in recording techniques, the inner working of these populations has come into full view. Analyzing the resulting large-scale data sets is challenging because of the often complex and ‘mixed’ dependency of neural activities on experimental parameters, such as stimuli, decisions, or motor responses. Here we review recent insights gained from analyzing these data with dimensionality reduction methods that ‘demix’ these dependencies. We demonstrate that the mappings from (carefully chosen) experimental parameters to population activities appear to be typical and stable across tasks, brain areas, and animals, and are often identifiable by linear methods. By considering when and why dimensionality reduction and demixing work well, we argue for a view of population coding in which populations represent (demixed) latent signals, corresponding to stimuli, decisions, motor responses, and so on. These latent signals are encoded into neural population activity via non-linear mappings and decoded via linear readouts. We explain how such a scheme can facilitate the propagation of information across cortical areas, and we review neural network architectures that can reproduce the encoding and decoding of latent signals in population activities. These architectures promise a link from the biophysics of single neurons to the activities of neural populations.