A transcriptomic axis predicts state modulation of cortical interneurons

Abstract

Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes1–6, but it is not known whether these subtypes have correspondingly diverse patterns of activity in the living brain. Here we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, which are organized by a single factor: position along the main axis of transcriptomic variation. We combined in vivo two-photon calcium imaging of mouse V1 with a transcriptomic method to identify mRNA for 72 selected genes in ex vivo slices. We classified inhibitory neurons imaged in layers 1–3 into a three-level hierarchy of 5 subclasses, 11 types and 35 subtypes using previously defined transcriptomic clusters3. Responses to visual stimuli differed significantly only between subclasses, with cells in the Sncg subclass uniformly suppressed, and cells in the other subclasses predominantly excited. Modulation by brain state differed at all hierarchical levels but could be largely predicted from the first transcriptomic principal component, which also predicted correlations with simultaneously recorded cells. Inhibitory subtypes that fired more in resting, oscillatory brain states had a smaller fraction of their axonal projections in layer 1, narrower spikes, lower input resistance and weaker adaptation as determined in vitro7, and expressed more inhibitory cholinergic receptors. Subtypes that fired more during arousal had the opposite properties. Thus, a simple principle may largely explain how diverse inhibitory V1 subtypes shape state-dependent cortical processing.

Cortical somatostatin interneuron subtypes form cell-type specific circuits

“…The rapid expansion of single-cell transcriptomic analysis of cell type taxonomies in recent years has resulted in an unprecedented understanding of the molecular heterogeneity of cortical neurons (Callaway et al, 2021;Ecker et al, 2017;Ngai, 2022). However, despite recent efforts (Berg et al, 2021;Bugeon et al, 2022;Cadwell et al, 2016;Condylis et al, 2022;Fuzik et al, 2016;Gouwens et al, 2020;Kim et al, 2020;Scala et al, 2021;Tasic et al, 2016Tasic et al, , 2018, an understanding of how transcriptomic cell type correlates with other modalities including morphology, connectivity and in vivo functions are still largely lacking. In this study, we developed and characterized genetic strategies to target the breadth of transcriptomically identified SST subtypes.…”

Independent response modulation of visual cortical neurons by attentional and behavioral states

“…Neuron 110, 1-12, December 7, 2022Please cite this article in press as: Kanamori and Mrsic-Flogel, Independent response modulation of visual cortical neurons by attentional and behavioral states, Neuron(2022), https://doi.org/10.1016/j.neuron.2022.08.028 …”

Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner

“…Lastly, KOR activation inhibited BLA inputs to non-fast spiking SOM neurons but not fast-spiking PV-positive interneurons, suggesting that KOR-lacking and KOR-expressing BLA inputs may differentially engage inhibitory mPFC microcircuits. Within mPFC circuits, multi-plexed encoding of information may in part be defined by projection patterns, molecular signatures, and/or localization of neurons across cortical layers, factors that are in large part inter-related (Otis et al, 2017; Ye et al, 2016; Condylis et al, 2022; Bugeon et al, 2022). Within the mPFC, Dyn and KOR-expressing neurons are found in different layers, raising the possibility that these different populations of neurons may differentially contribute to processing of limbic information and executive function.…”