An Unexpected Dependence of Cortical Depth in Shaping Neural Responsiveness and Selectivity in Mouse Visual Cortex

Abstract

Two-photon imaging studies in mouse primary visual cortex (V1) consistently report that around half of the neurons respond to oriented grating stimuli. However, in cats and primates, nearly all neurons respond to such stimuli. Here we show that mouse V1 responsiveness and selectivity strongly depends on neuronal depth. Moving from superficial layer 2 down to layer 4, the percentage of visually responsive neurons nearly doubled, ultimately reaching levels similar to what is seen in other species. Over this span, the amplitude of neuronal responses also doubled. Moreover, stimulus selectivity was also modulated, not only with depth but also with response amplitude. Specifically, we found that orientation and direction selectivity were greater in stronger responding neurons, but orientation selectivity decreased with depth whereas direction selectivity increased. Importantly, these depth-dependent trends were found not just between layer 2/3 and layer 4 but at different depths within layer 2/3 itself. Thus, neuronal depth is an important factor to consider when pooling neurons for population analyses. Furthermore, the inability to drive the majority of cells in superficial layer 2/3 of mouse V1 with grating stimuli indicates that there may be fundamental differences in the micro-circuitry and role of V1 between rodents and other mammals.

Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex

“…In vivo L2/3 pyramidal cells show depth-dependent variations in stimulus response amplitude and ocular dominance, but not in tuning heterogeneity How do the observed gradual changes in the different properties relate to visual responses of L2/3 PyrCs in bV1 in vivo? Previous recordings in L2/3 of mouse monocular V1 showed a gradual change in overall responsiveness and orientation as well as direction selectivity with pial depth (O'Herron et al, 2020). However, the depth-dependent distribution of other features like eye-specific responsiveness have remained unaddressed so far.…”

“…This suggests that, rather than originating from discrete, spatially intermingled neuronal subtypes, functional and structural features of L2/3 PyrCs may vary continuously or follow larger scale anatomical gradients, like cortical depth. Indeed, structural, molecular and functional characteristics of L2/3 neurons were found to vary with distance from pia (Kreile et al, 2011;Staiger et al, 2015;Tasic et al, 2016;Gouwens et al, 2019;O'Herron et al, 2020).…”

Sensing and processing whisker deflections in rodents

“…This sensory information is then projected up to layers II and III for further processing (along with other local cortical areas), then down to layers V and VI for final output to more distant cortical areas, such as motor cortex (as well as sending feedback to sub-cortical areas) ( Radnikow, Qi & Feldmeyer, 2015 ). Layer IV excitatory cells typically have strong, narrow tuning to single whiskers while cells in supra- and infra-granular layers typically show broader, mixed-strength tuning (indicating tuning to more precise, higher-order features, and possibly common to multiple whiskers, as indicated by generally narrower receptive fields in layer IV compared to other layers ( Brecht, Roth & Sakmann, 2003 ; Brecht & Sakmann, 2002 ) and more complex sensory information generally being computed and integrated in cortex in layers other than layer IV ( Bale & Maravall, 2018 ; Lyall et al, 2020 ; O’Herron et al, 2020 )). Neurons across all layers, but particularly infragranular layers, can be tuned to temporal or qualitative features of whisker deflection, e.g., directional sensitivity or initial versus sustained parts of deflection.…”

“…On average, most of these interneurons will synapse onto three to six pyramidal neurons in layer II and III and make similar kinds and numbers of connections with layer V pyramidal neurons. These interneuronal connections onto layer II and III pyramidal cells, in combination with the intricate excitatory connection patterns from layer IV and thalamus, allows cells to be finely tuned to complex, higher-order features of sensory input ( Bale & Maravall, 2018 ; Lyall et al, 2020 ; O’Herron et al, 2020 ).…”

Cortical layer-specific differences in stimulus selectivity revealed with high-field fMRI and single-vessel resolution optical imaging of the primary visual cortex

“…Instead each patch has a rich laminar organization of neural circuitry that results in predictable changes in neural selectivity across cortical layers. Specifically for orientation selectivity in the primary visual cortex (V1), single-neuron responses from rodent and non-rodent mammals show that orientation selectivity changes systematically across cortical layers ( O’Herron et al, 2020 ; Ringach et al, 2002 ; Van Hooser et al, 2013 ). The most recent of these studies attributes the laminar differences in selectivity to the location of thalamic inputs being largely confined to cortical layer 4 and these thalamic inputs having very weak orientation selectivity ( Chung and Ferster, 1998 ; Ferster et al, 1996 ; Kara et al, 2002 ; O’Herron et al, 2020 ).…”