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

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

“…The extent and near symmetry of the long, diffuse, intrinsic horizontal axonal radiation we report here and elsewhere (Frostig et al 2008; Stehberg et al 2014; Johnson and Frostig 2015) have not been discussed in the numerous prior studies of cortico-cortical efferent connections of barrel cortex. Long horizontal connections between neurons in other sensory cortices have been established in multiple species (see, for example, Stettler et al 2002; Martin et al 2014).…”

“…Following supragranular vector injections, there was a remarkable similarity in the horizontal axonal projection pattern at different cortical depths, representing axons in both supragranular and infragranular laminae (Johnson and Frostig 2015). This similarity was clearly evident in individual brains, and the average pattern further revealed that the general characteristics of a diffuse radiation of axons occurred at all depths that we investigated.…”

“…Recently, other researchers working on elucidating the cortical connectome have accumulated data suggesting more profuse efferent projections from the rat (Zakiewicz et al 2014) and mouse (Zingg et al 2014; Oh et al 2014) barrel cortex than were reported in early studies, although the coronal section plane and comprehensive mapping strategies preferred in these reports likely obscure the radiating nature of the mesoscopic projection (Johnson and Frostig 2015). Indeed, the data mining in the analysis of the connectome typically imposes preconceived notions of cortical parcellation that would divide some of the continuous patterns of connectivity we have described into discrete regions before quantitative comparisons are performed (Bota et al 2012; Zingg et al 2014; Oh et al 2014).…”

“…To distinguish adequately a relatively sparse projection from false detection of fibers, we used a statistical approach involving injections into the same cortical region in multiple animals, whereas fewer injections into each of multiple distinct locations are employed by others to complete the connectome (Zingg et al 2014; Oh et al 2014). Likewise, the sparsity of fibers encouraged us to perform axonal reconstructions across a large set of meticulously aligned adjacent histological sections, a detailed strategy not currently exploited in the analysis of the connectome (Johnson and Frostig 2015). A combination of “big data” approaches such as the connectome projects and approaches targeted to answering specific questions such as we have done here is still required for a thorough understanding of cortical connectivity and function.…”

“…Whisker representations in the posterior medial barrel subfield (PMBSF) of the rodent primary somatosensory cortex (SI), popularly known as “barrel cortex,” have provided convenient animal models for interventive research into these principles of cortical structure and function (reviewed in Feldmeyer et al 2013). However, based on functional imaging, neuronal recordings from microelectrode arrays, and histological tract tracing, research from our lab has suggested the existence of an additional, horizontally oriented system in barrel cortex and in other primary sensory cortices that is not clearly evident in current versions of the connectome and that creates a gray matter functional and structural continuum within sensory neocortex (Frostig et al 2008; Chen-Bee et al 2012; Stehberg et al 2014; Johnson and Frostig, 2015). …”