Long-Range, Border-Crossing, Horizontal Axon Radiations Are a Common Feature of Rat Neocortical Regions That Differ in Cytoarchitecture.

Brett A Johnson,Ron D Frostig

doi:10.3389/fnana.2018.00050

Abstract

Employing wide-field optical imaging techniques supported by electrophysiological recordings, previous studies have demonstrated that stimulation of a spatially restricted area (point) in the sensory periphery results in a large evoked neuronal activity spread in mammalian primary cortices. In rats’ primary cortices, such large evoked spreads extend diffusely in multiple directions, cross cortical cytoarchitectural borders and can trespass into other unimodal sensory areas. These point spreads are supported by a spatially matching, diffuse set of long-range horizontal projections within gray matter that extend in multiple directions and cross borders to interconnect different cortical areas. This horizontal projection system is in addition to well-known area-to-area clustered projections to defined targets through white matter. Could similar two-projection cortical systems also be found in cortical regions that differ in their cytoarchitectural structure? To address this question, an adeno-associated viral vector expressing green fluorescent protein (GFP) was injected as an anterograde tract tracer into granular somatosensory cortex (trunk area), dysgranular cortex (somatosensory dysgranular zone and extrastriate cortex) and agranular motor cortex (MCx). Irrespective of the injection site the same two projection systems were found, and their quantification revealed a close similarity to findings in primary sensory cortices. Following detailed reconstruction, the diffuse horizontal axon radiation was found to possess numerous varicosities and to include short, medium and long axons, the latter extending up to 5.2 mm. These “proof of concept” findings suggest that the similarity of the two projection systems among different cortical areas could potentially constitute a canonical motif of neocortical organization.

Highlights

Accumulating evidence from functional imaging and electrophysiological studies has demonstrated that stimulating a spatially restricted area (‘‘point’’ stimulation; e.g., a whisker, a pure tone, or small visual stimulation) in the sensory periphery results in a functional point-spread: a large, roughly symmetrical, diffuse activation, with a radius of several millimeters, in primary sensory cortices, Horizontal Axon Radiations Across Neocortex including somatosensory, auditory and visual cortices
Electrophysiological analyses of the lateral spreads of activity initiated by microstimulation in mouse VCx (Fehervari et al, 2015) and cat MCx (Capaday et al, 2011) are consistent with an involvement of long-range, thin horizontal axons for at least part of this propagation of activity. These results suggest that activity initiated at different points in cortex can spread across large cortical distances by way of diffuse horizontal projections, which encourages extending our concepts of cortical structure-function relationships
While further research is needed, our findings suggest that potentially every point in cortex is likely a source and recipient of horizontal axonal projections, including long-range horizontal projections, and some of those very long horizontal projections ignore cortical cytoarchitectonic borders

Summary

Introduction

Accumulating evidence from functional imaging and electrophysiological studies has demonstrated that stimulating a spatially restricted area (‘‘point’’ stimulation; e.g., a whisker, a pure tone, or small visual stimulation) in the sensory periphery results in a functional point-spread: a large, roughly symmetrical, diffuse activation, with a radius of several millimeters, in primary sensory cortices, Horizontal Axon Radiations Across Neocortex including somatosensory, auditory and visual cortices (reviewed in Frostig et al, 2017). The major question that the current project seeks to address is whether the ‘‘twosystems’’ concept is unique to granular primary sensory cortices or whether it might extend to all other known types of neocortical areas including dysgranular and agranular cortices To address this question, we have repeated our previous anatomical investigation strategy as employed in the PMBSF, using small AAV virus injections into dysgranular and agranular cortical areas to cause expression of enhanced green fluorescent protein (GFP) under a cytomegalovirus (CMV) promoter (Johnson and Frostig, 2016). These characteristics include a large and relatively symmetrical spatial extent, ability to cross borders into other cortical areas, and a smooth decline over cortical distance—suggesting together a spatial correspondence between anatomical and functional pointspreads

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