Abstract

The orbitofrontal cortex (OFC) has been anatomically divided into a number of subregions along its medial–lateral axis, which behavioral research suggests have distinct functions. Recently, evidence has emerged suggesting functional diversity is also present along the anterior–posterior axis of the rodent OFC. However, the patterns of anatomical connections that underlie these differences have not been well characterized. Here, we use the retrograde tracer cholera toxin subunit B (CTB) to simultaneously label the projections into the anterior lateral (ALO), posterior lateral (PLO), and posterior ventral (PVO) portions of the rat OFC. Our methodological approach allowed us to simultaneously compare the density and input patterns into these OFC subdivisions. We observed distinct and topographically organized projection patterns into ALO, PLO, and PVO from the mediodorsal and the submedius nuclei of the thalamus. We also observed different levels of connectivity strength into these OFC subdivisions from the amygdala, motor cortex, sensory cortices and medial prefrontal cortical structures, including medial OFC, infralimbic and prelimbic cortices. Interestingly, while labelling in some of these input regions revealed only a gradient in connectivity strength, other regions seem to project almost exclusively to specific OFC subdivisions. Moreover, differences in input patterns between ALO and PLO were as pronounced as those between PLO and PVO. Together, our results support the existence of distinct anatomical circuits within lateral OFC along its anterior–posterior axis.

Highlights

  • Over recent years there has been an increasing understanding that the rodent orbitofrontal cortex (OFC) is not functionally homogeneous, along its medial–lateral axis

  • The location of the core injection deposits included in the analysis were mostly confined to the intended OFC subdivision, with some extension into the ventral agranular insula (AIv) from the posterior lateral OFC (PLO) injections

  • Our approach allowed us to assess the extent of overlap, convergence and divergence between the projections of these OFC subdivisions, and define their topographic relationships

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Summary

INTRODUCTION

Over recent years there has been an increasing understanding that the rodent orbitofrontal cortex (OFC) is not functionally homogeneous, along its medial–lateral axis (see Barreiros et al, 2021; Bradfield and Hart, 2020; Izquierdo, 2017 for reviews). Another study revealed that the anterior but not posterior portion of MO is critical for inferring unobservable actiondependent outcomes and for behavioral response adaptation in outcome-devaluation tasks (Bradfield et al, 2018) These findings suggest that, rather than functionally uniform, the currently recognized OFC subregions might be composed of smaller structural and functional regions along its anterior–posterior axis. We test the hypothesis that there are distinct anatomical projections to the anterior lateral (ALO) and posterior lateral OFC (PLO) that underlie the functional dissociation reported by Panayi and Killcross (2018). These anterior–posterior anatomical distinctions within lateral OFC support the emerging functional heterogeneity within this region

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