PT - JOURNAL ARTICLE AU - William G. P. Mayner AU - William Marshall AU - Yazan N. Billeh AU - Saurabh R. Gandhi AU - Shiella Caldejon AU - Andrew Cho AU - Fiona Griffin AU - Nicole Hancock AU - Sophie Lambert AU - Eric K. Lee AU - Jennifer A. Luviano AU - Kyla Mace AU - Chelsea Nayan AU - Thuyanh V. Nguyen AU - Kat North AU - Sam Seid AU - Ali Williford AU - Chiara Cirelli AU - Peter A. Groblewski AU - Jerome Lecoq AU - Giulio Tononi AU - Christof Koch AU - Anton Arkhipov TI - Measuring Stimulus-Evoked Neurophysiological Differentiation in Distinct Populations of Neurons in Mouse Visual Cortex AID - 10.1523/ENEURO.0280-21.2021 DP - 2022 Jan 01 TA - eneuro PG - ENEURO.0280-21.2021 VI - 9 IP - 1 4099 - http://www.eneuro.org/content/9/1/ENEURO.0280-21.2021.short 4100 - http://www.eneuro.org/content/9/1/ENEURO.0280-21.2021.full SO - eNeuro2022 Jan 01; 9 AB - Despite significant progress in understanding neural coding, it remains unclear how the coordinated activity of large populations of neurons relates to what an observer actually perceives. Since neurophysiological differences must underlie differences among percepts, differentiation analysis—quantifying distinct patterns of neurophysiological activity—has been proposed as an “inside-out” approach that addresses this question. This methodology contrasts with “outside-in” approaches such as feature tuning and decoding analyses, which are defined in terms of extrinsic experimental variables. Here, we used two-photon calcium imaging in mice of both sexes to systematically survey stimulus-evoked neurophysiological differentiation (ND) in excitatory neuronal populations in layers (L)2/3, L4, and L5 across five visual cortical areas (primary, lateromedial, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater ND than scrambled stimuli specifically in L2/3 of the anterolateral and anteromedial areas, and that this effect is modulated by arousal state and locomotion. By contrast, decoding performance was far above chance and did not vary substantially across areas and layers. Differentiation also differed within the unscrambled stimulus set, suggesting that differentiation analysis may be used to probe the ethological relevance of individual stimuli.