Hierarchy in sensory processing reflected by innervation balance on cortical interneurons

Abstract

Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV+) and vasoactive intestinal peptide–positive (VIP+) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV+ and VIP+ neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.

Neuronal cell-type and circuit basis for visual predictive processing

“…Unilateral viral injections were made at superficial locations of V1, and we quantified ipsilateral neocortical input density to V1 VIP INs. Our tracing results confirm V1 L2/3 VIP INs are directly innervated by distal monosynaptic excitatory top-down projections from ipsilateral motion-planning cortical regions 36 (Fig. 2i&j).…”

“…Detail of histology has been published elsewhere 36 . After embedding and freezing, the brain was sectioned into 50-μm coronal slices using a cryostat.…”

“…We chose to first focus on V1 L2/3 VIP INs due to their extensive innervations by top-down projections 36 and importance demonstrated in predictive processing-associated cognitive functions such as learning and attention 37-41 .…”

“…V1 VIP INs receive top-down, bottom-up and local recurrent excitatory inputs 36-40 . To delineate the interplay between top-down and bottom-up pathways pertaining to pre-running VIP activation, we examined the peri-running activities of V1 local L2/3 Pyr neurons (n = 378 ROIs in 9 FOVs, Fig.…”

“…Viral injections. Viral vectors were prepared as published previously36,39 . For retrograde monosynaptic tracing Glycoprotein-deleted (ΔG) and EnvA-pseudotyped rabies virus (RV-ΔG-EGFP+EnvA, 2.4 × 10 8 IU/mL), AAV2-CAG-DIO-TVA-mCherry (2.1 × 10 13 gc/mL) and AAV2-CAG-DIO-Glycoprotein (8.7 × 10 12 gc/mL) were used.…”