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

Abstract

Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. These PyrCs show pial depth-dependent functional and structural specializations, indicating participation in different functional microcircuits. However, whether these depth-dependent differences result from separable PyrC subtypes or whether their features display a continuum correlated with pial depth is unknown. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory connectivity across the depth of L2/3 in the binocular visual cortex of mice. We find that the apical, but not the basal dendritic tree structure, varies with pial depth, which is accompanied by variation in subthreshold electrophysiological properties. Lower L2/3 PyrCs receive increased input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. In vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper PyrCs are more driven by contralateral than ipsilateral eye stimulation. Importantly, the property value transitions are gradual, and L2/3 PyrCs do not display discrete subtypes based on these parameters. Therefore, L2/3 PyrCs’ multiple functional and structural properties systematically correlate with their depth, forming a continuum rather than discrete subtypes.

Cellular and circuit mechanisms underlying binocular vision

“…Consistent with this idea, we found that the excitability of binocular neurons was negatively correlated with the strength of both callosal and ipsilateral eye input. These data are consistent with recent studies which suggest that L2/3 pyramidal neurons in the superficial layers of binocular V1 are organized as a continuum and show a gradient in terms of their molecular (Cheng et al, 2022;Kim et al, 2020;Tan et al, 2020) and electrophysiological properties (Weiler et al, 2023).…”

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex

“…Finally, in around 30% of cells using 3 µM muscarine, only an ADP with no spiking was observed. This variability might be due to heterogeneity in the tested sample of cells, perhaps reflecting subsets of cells with different sets of channels or receptors (Luo et al ., 2017; Karimi et al ., 2020; Weiler et al ., 2023). The probability of generating a spiking PP was also greatly dependent on the concentration of muscarine used ( Figure 2C ).…”

Computational components of visual predictive coding circuitry

“…The recordings were made in alert but passively behaving subjects, and could yet be consistent with an intrinsic modulatory role, in contrast to FF neurons in layer 3 with better capability to transmit specific, focal image features. Layer 2 also showed significantly higher spontaneous activity, perhaps consonant with a couple of electrical characteristics of neurons in layer 2 of mouse V1 -higher membrane input resistance and longer time constants -as noted by Weiler et al (2023). Whilst, therefore, FB precision signalling finds an initial, if tenuous foothold in generic physiology, the nature of FF error signalling is more securely rooted in well-documented aspects of cellular electrophysiology and neural dynamics (Section 3.3).…”

“…By comparison, pyramid neurons lying more superficially are observed to have more profuse apical arborisations in layers 1 and 2. Of note, a corresponding continuum has been quantitatively documented in layer 2/3 of mouse V1, where pyramid neurons lying more superficially receive progressively less input from layer 4, and have progressively broader apical dendritic trees ( Weiler et al, 2023 ). In macaque V2, layer 3B houses the forward pathway, posited to comprise EXP and ERR pyramid neurons.…”