Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex

Abstract

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—is an “inside out” approach that addresses this question. We used two-photon calcium imaging in mice to systematically survey stimulus-evoked neurophysiological differentiation in excitatory populations across 3 cortical layers (L2/3, L4, and L5) in each of 5 visual cortical areas (primary, lateral, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater neurophysiological differentiation than scrambled stimuli specifically in L2/3 of the anterolateral and anteromedial areas, and that this effect is modulated by arousal state and locomotion. Contrariwise, 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.

A survey of neurophysiological differentiation across mouse visual brain areas and timescales

“…A recent calcium imaging study showed that the ND of cellular fluorescent responses was higher for naturalistic stimuli (movies of predators and prey) compared to phase-scrambled versions of the same movies in in layer 2/3 of two specific regions of the mouse brain, VISal and VISam. In layers 4 and 5 of the same areas and in all layers of the other areas studied (VISp, VISl, and VISpm), the difference was non-significant (Mayner et al, 2022). In contrast, activity in any recorded visual cortical layer and region could be used to accurately decode stimulus type (naturalistic vs. scrambled).…”

“…Thus, the richness of perceptual experience ("meaningfulness of stimuli") should correspond to the richness of neural activity (and not the richness of the stimulus) in the specific neuronal populations that are the physical substrate of the perceptual experience. This richness of neural activity has been quantified in several recent studies by measuring how many different states the brain or a specific brain region enters during a period of time, called neurophysiological differentiation (ND) (Synek, 1988;Gosseries et al, 2011;Barttfeld et al, 2015;Boly et al, 2015;Hudetz et al, 2015;Solovey et al, 2015;Mayner et al, 2022).…”