Long, intrinsic horizontal axons radiating through and beyond rat barrel cortex have spatial distributions similar to horizontal spreads of activity evoked by whisker stimulation

Abstract

Stimulation of a single whisker evokes a peak of activity that is centered over the associated barrel in rat primary somatosensory cortex, and yet the evoked local field potential and the intrinsic signal optical imaging response spread symmetrically away from this barrel for over 3.5 mm to cross cytoarchitectonic borders into other “unimodal” sensory cortical areas. To determine whether long horizontal axons have the spatial distribution necessary to underlie this activity spread, we injected adeno-associated viral vectors into barrel cortex and characterized labeled axons extending from the injection site in transverse sections of flattened cortex. A combined qualitative and quantitative analysis revealed labeled axons radiating diffusely in all directions for over 3.5 mm from supragranular injection sites, with density declining over distance. The projection pattern was similar at four different cortical depths, including infragranular laminae. Infragranular vector injections produced patterns similar to the supragranular injections. Long horizontal axons were detected both using a vector with a permissive CMV promoter to label all neuronal subtypes and using a CaMKIIα vector to restrict labeling to excitatory cortical pyramidal neurons. Individual axons were successfully reconstructed from series of supragranular sections, indicating that they traversed gray matter only. Reconstructed axons extended from the injection site, left the barrel field, branched, and sometimes crossed into other sensory cortices identified by cytochrome oxidase staining. Thus, radiations of long horizontal axons indeed have the spatial characteristics necessary to explain horizontal activity spreads. These axons may contribute to multimodal cortical responses and various forms of cortical neural plasticity.

Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams

“…Namely, a dynamic shift from a CP signaling by strong horizontal connectivity may undergo a rebalancing by its weakening (Brodal 2007) as confirmed in literature (Schnepel et al 2015;Angelucci and Bressloff 2006;Négyessy et al 2013). Indeed, because intrinsic horizontal connections appear crucially involved in the rat primary somatosensory cortex tasks (Négyessy et al 2013), we can reasonably assume a similar involvement in the pain processing (B A Johnson and Frostig 2016;Brett A Johnson and Frostig 2018). The advantage of a conversion from a CP statistically stationary structure to an artificial modular complex able to augment and improve the information content is ratified, also, by the potential advantages of partitioned architectures, as shown in many biological contexts (Bullmore and Sporns 2012).…”

“…With the assumption that CP appears too much a complex multiscale disorders, we conjectured that a widely encompassing intervention focussed on the physical re-arrangement of the involved thalamocortical network architectures could prompt concurrent modifications in the information processing leading to sensory re-conversion back to match control conditions (Francis and Song 2011). From an anatomo-functional point of view, the dense cortical somatotopic projections are characterized by dynamic borders maintained on a delicate balance of excitation/inhibition through the cortical circuits, especially with horizontal connections (B A Johnson and Frostig 2016;Brett A Johnson and Frostig 2018;Négyessy et al 2013). These refined networks, designing a functional modularity in the cortical somatotopic projection fields, undergo a failure in CP with integer contiguity loss and a derangement of projection field independence.…”

Structured networks support sparse traveling waves in rodent somatosensory cortex

“…1D) (8,9), but the cortical circuits that support the activity propagation have not been previously explored. There is evidence that the activity propagation in the rodent barrel cortex could be supported by strong horizontal connections (20) [although intracolumnar interactions across layers may also contribute to the activity propagation (21)]. We will show that the observed salt-and-pepper tuning, low average responsiveness, and the existence of a population of more reliably responding L2/3 neurons in the rodent barrel cortex can all be explained by activity propagation within L2/3.…”

Photonics meets connectomics: case of diffuse, long-range horizontal projections in rat cortex

“…Numerous long, border-crossing horizontal axons also have been reconstructed from brains injected with an rAAV vector employing a calciumcalmodulin dependent protein kinase II alpha (CaMKIIα) promoter. 42 Because this promoter should restrict expression to excitatory cortical pyramidal neurons, the horizontal projection system likely includes axon collaterals from these cells. Having established the existence of the horizontal projection system in slices of flattened cortices after injections of three different anterograde tracers (BDA and rAAV vectors using both CMV and CaMKIIα promoters), we will now discuss the extent to which this system is evident in current versions of the mouse connectome.…”