Parallel organization of contralateral and ipsilateral prefrontal cortical projections in the rhesus monkey

Helen Barbas,Subhash Saha,Caterina R Dermon,Joanna L Suski,Claus C Hilgetag

doi:10.1186/1471-2202-6-32

Helen Barbas, Subhash Saha + Show 3 more

Open Access

https://doi.org/10.1186/1471-2202-6-32

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Abstract

BackgroundThe neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas.ResultsCommissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area.ConclusionThe organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.

Highlights

The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres
Single injections of tracer at each site labeled many cortical neurons in several ipsilateral areas, as well as neurons in many of the same areas on the contralateral side (3–11 areas, median 9; Fig. 2B). In addition to this wide distribution of contralateral labeling, there were strong and significant correlations between the relative density patterns of ipsilateral and contralateral projections for all injection sites (Pearson's correlation, p < 0.05), except for injections in area 13 [13(1), 13 (2); cases AJb, ALb] that resulted in slightly higher probability values (p = 0.071, p = 0.051, respectively; Fig. 2C). This demonstrated that the areal distribution and density pattern of contralateral projections overlapped with a substantial subset of projections in the same areas on the ipsilateral hemisphere, despite the much lower absolute density of contralateral projection neurons
Since projections arise as different layers are generated, a punctuated course of development of prefrontal areas could provide a mechanism for the graded laminar distribution of projections that we showed for ipsilateral connections [15] and for contralateral projections here

Summary

Introduction

The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. Categorical types of cortices can be determined by the number of cortical layers, thickness of layer IV, and density of neurons and other cellular markers [16]. Within this scheme, ipsilateral projections emanate from layers II-III when issued from areas with more layers, or denser layer IV, in comparison with the area of termination. Projection neurons originate predominantly in layers V-VI This hypothesis has received support in the ipsilateral connections of prefrontal areas with each other [15], and with distant sensory and association areas [17,18,19,20]

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