Switches in Orientation Coding by Mouse Primary Visual Cortex Neurons Depend on Stimulus Predictability

How the brain processes a stimulus depends on contextual factors, such as whether it is predictable or surprising. While this process has been partially characterized using EEG and fMRI, and invasive cellular approaches, the microcircuit mechanisms responsible for comparing sensory input and expectations remain poorly understood. Here, we combined layer-resolved recordings of single-unit activity and local field potentials (LFP) in mouse primary visual cortex (V1) with a visual oddball paradigm using oriented gratings. Both event-related potentials and firing rates exhibited distinct temporal components across cortical layers and trial types. We identified robust stimulus-specific adaptation (SSA), mismatch negativity (MMN), and deviant detection (DD) contrast at both early and late epochs. Surprisingly, a substantial subset of excitatory neurons exhibited complete reversals of orientation preference (“preference switches”) between standard and deviant trials, rather than only changes in selectivity. These preference-switching cells were primarily observed in layers 2/3 and 5/6 and contributed as much information to stimulus decoding as stably tuned neurons. Our findings demonstrate that context-dependent flexibility in feature preference is an integral part of predictive coding in V1 and challenge the notion of fixed stimulus representations at the single-neuron level.