Dense functional and molecular readout of a circuit hub in sensory cortex

Abstract

Cell type diversity in the neocortex The ability to link molecularly identified neurons with their function during behavior requires monitoring the activity of these cell types in vivo. Condylis et al . developed a platform for population functional imaging with spatial transcriptomics. Using newly acquired transcriptomic cell census data from the Allen Institute for Brain Science, the authors studied the function of cell types in primary somatosensory cortex in mice performing a tactile working memory task. Task-related properties of both excitatory and inhibitory neurons continued to differentiate as they were segregated into increasingly discrete molecular types. A new excitatory cell type, Baz1a, formed a sensory-driven circuit hub that orchestrates local sensory processing in superficial layers of the neocortex. This approach opens new venues for exploring information processing in the brain. —PRS

A transcriptomic axis predicts state modulation of cortical interneurons

“…We did not use statistical methods to pre-determine sample sizes. However, our sample sizes are similar to those reported in previous publications using a similar approach 25 , 26 . Our study did not contain experimental groups, so randomization and blinding do not apply.…”

Prediction error neurons in mouse cortex are molecularly targetable cell types

“…The Agmat type was underrepresented in both high visuomotor mismatch and low grating photoconversion groups ( Figure 2G ), and the L2/3 Rrad type was significantly overrepresented in the high grating photoconversion group ( Figure 2H ). These results suggest that on average visuomotor mismatch responsive neurons are enriched in the L2/3 Adamts2 cell type, and that, consistent with previous findings (Condylis et al, 2022), neurons responding to feed-forward sensory stimuli are enriched in the L2/3 Rrad cell type. The remaining L2/3 Agmat type appears to represent an intermediate population or potentially a grouping with an as yet unidentified function.…”

“…We hypothesized that the L2/3 excitatory cell types might have different functional response properties. In the case of the L2/3 Rrad type, it has been found in barrel cortex of mice that Baz1a positive neurons (one of the marker genes of the Rrad type) are highly responsive to sensory stimuli (Condylis et al, 2022). To test whether each of these cell types had distinct functional response properties, we investigated whether there was a differential enrichment of the three L2/3 excitatory cell types ( Adamts2, Agmat or Rrad ) across stimulus paradigms (visuomotor mismatch, running onsets in darkness, or grating onsets) and photoconversion state (low, medium, or high).…”

“…These L2/3 excitatory cell types correspond to layer 2 (L2) and layer 3 (L3) transcriptional classes of excitatory neurons found in human cortex (Hodge et al, 2019). In somatosensory cortex, it has been demonstrated that the L2/3 Rrad type is largely driven by feedforward sensory input (Condylis et al, 2022), and in inhibitory neurons it has recently been found that a specific transcriptomic axis predicts how a neuron is functionally modulated by locomotion (Bugeon et al, 2022). Thus, we speculated that positive and negative prediction error neurons can be mapped onto transcriptionally defined neuron types within L2/3 of V1.…”

Membrane potential dynamics of excitatory and inhibitory neurons in mouse barrel cortex during active whisker sensing

“…Indeed, as the number of different subclasses of neurons increases, the approach of studying these through whole-cell recordings becomes less feasible due to the technical difficulty in obtaining these recordings. Fortunately, the signal-to-noise ratio of fluorescent V m sensors for in vivo imaging with cellular resolution is rapidly increasing (Villette et al, 2019), and this methodology will likely be necessary to examine many subclasses of GABAergic and excitatory neurons in combination with fluorescence in situ hybridisation (FISH) to molecularly characterize cell types (Condylis et al, 2022).…”