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      Organization of Afferents along the Anterior–posterior and Medial–lateral Axes of the Rat Orbitofrontal Cortex

      research-article
      a , b , c , * , 1 , a , c , * , 1 , a , c , *
      Neuroscience
      Elsevier Science
      a24b, anterior cingulate cortex, area 24b, AI, d, v, P, agranular insular cortex, dorsal, ventral, posterior parts, ALO, lateral orbitofrontal cortex, anterior part, Au1, auditory cortex, primary area, AVO, ventral orbitofrontal cortex, anterior part, BLA, basolateral nucleus of amygdala, BLP, basolateral nucleus of the amygdala, posterior part, DLO, dorsolateral orbitofrontal cortex, GI, granular insular cortex, IL, infralimbic cortex, LaDL, lateral amygdala, dorsolateral part, LaVL, lateral amygdala, ventrolateral part, LaVM, lateral amygdala, ventromedial part, Lent, lateral entorhinal cortex, LO, lateral orbitofrontal cortex, M1, primary motor cortex, M2, secondary motor cortex, MD, m, c, l, mediodorsal nucleus of the thalamus, medial, central, lateral parts, MO, medial orbitofrontal cortex, Pir, piriform cortex, PL, prelimbic cortex, PLO, lateral orbitofrontal cortex, posterior part, PRh, perirhinal cortex, PT, paratenial nucleus of the thalamus, PVO, ventral orbitofrontal cortex, posterior part, Re, nucleus reuniens of the thalamus, RS, retrosplenial cortex, S1BF, primary somatosensory cortex, barrel field, S1J, primary somatosensory cortex, jaw region, S1HL/FL, primary somatosensory cortex, hindlimb and forelimb regions, S1Tr, primary somatosensory cortex, trunk region, S2, secondary somatosensory cortex, Sub, D, V, submedius nucleus of the thalamus, dorsal, ventral parts, V2, secondary visual cortex, VO, ventral orbitofrontal cortex, amygdala, neuroanatomy, rostral–caudal, rodent, submedius nucleus, thalamus

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          Graphical abstract

          Highlights

          • Distinct anatomical inputs define anterior and posterior regions in rat lateral OFC.

          • Anterior–posterior differences as distinct as established medial–lateral ones in OFC.

          • Amygdala inputs to OFC predominantly target posterior lateral OFC.

          • Submedius thalamic input patterns are a key characteristic of distinct OFC subregions.

          • Anatomical heterogeneity within the OFC maps onto recent functional heterogeneity.

          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.

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          Most cited references57

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          Parallel organization of functionally segregated circuits linking basal ganglia and cortex.

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            The anatomical basis of functional localization in the cortex.

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              The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.

              This paper reviews architectonic subdivisions and connections of the orbital and medial prefrontal cortex (OMPFC) in rats, monkeys and humans. Cortico-cortical connections provide the basis for recognition of 'medial' and 'orbital' networks within the OMPFC. These networks also have distinct connections with structures in other parts of the brain. The orbital network receives sensory inputs from several modalities, including olfaction, taste, visceral afferents, somatic sensation and vision, which appear to be especially related to food or eating. In contrast, the medial network provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. The two networks have distinct connections with areas of the striatum and mediodorsal thalamus. In particular, projections to the nucleus accumbens and the adjacent ventromedial caudate and putamen arise predominantly from the medial network. Both networks also have extensive connections with limbic structures. Based on these and other observations, the OMPFC appears to function as a sensory-visceromotor link, especially for eating. This linkage appears to be critical for the guidance of reward-related behavior and for setting of mood. Imaging and histological observations on human brains indicate that clinical depressive disorders are associated with specific functional and cellular changes in the OMPFC, including activity and volume changes, and specific changes in the number of glial cells.

                Author and article information

                Contributors
                Journal
                Neuroscience
                Neuroscience
                Neuroscience
                Elsevier Science
                0306-4522
                1873-7544
                15 April 2021
                15 April 2021
                : 460
                : 53-68
                Affiliations
                [a ]Department of Experimental Psychology, University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK
                [b ]Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
                [c ]Wellcome Centre for Integrative Neuroimaging, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
                Author notes
                [* ]Corresponding authors. Address: Department of Experimental Psychology, University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK (I. V. Barreiros and M. E. Walton). National Institute on Drug Abuse, Biomedical Research Center, 251 Bayview Blvd. Baltimore, MD 21224, USA (M. C. Panayi). inesvbarreiros@ 123456gmail.com marios.panayi@ 123456nih.gov mark.walton@ 123456psy.ox.ac.uk
                [1]

                Equal contribution.

                Article
                S0306-4522(21)00090-7
                10.1016/j.neuroscience.2021.02.017
                8022030
                33609638
                b8207fbe-d38c-4e11-9725-0ab8e9748303
                © 2021 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 September 2020
                : 10 February 2021
                Categories
                Research Article

                Neurosciences
                a24b, anterior cingulate cortex, area 24b,ai, d, v, p, agranular insular cortex, dorsal, ventral, posterior parts,alo, lateral orbitofrontal cortex, anterior part,au1, auditory cortex, primary area,avo, ventral orbitofrontal cortex, anterior part,bla, basolateral nucleus of amygdala,blp, basolateral nucleus of the amygdala, posterior part,dlo, dorsolateral orbitofrontal cortex,gi, granular insular cortex,il, infralimbic cortex,ladl, lateral amygdala, dorsolateral part,lavl, lateral amygdala, ventrolateral part,lavm, lateral amygdala, ventromedial part,lent, lateral entorhinal cortex,lo, lateral orbitofrontal cortex,m1, primary motor cortex,m2, secondary motor cortex,md, m, c, l, mediodorsal nucleus of the thalamus, medial, central, lateral parts,mo, medial orbitofrontal cortex,pir, piriform cortex,pl, prelimbic cortex,plo, lateral orbitofrontal cortex, posterior part,prh, perirhinal cortex,pt, paratenial nucleus of the thalamus,pvo, ventral orbitofrontal cortex, posterior part,re, nucleus reuniens of the thalamus,rs, retrosplenial cortex,s1bf, primary somatosensory cortex, barrel field,s1j, primary somatosensory cortex, jaw region,s1hl/fl, primary somatosensory cortex, hindlimb and forelimb regions,s1tr, primary somatosensory cortex, trunk region,s2, secondary somatosensory cortex,sub, d, v, submedius nucleus of the thalamus, dorsal, ventral parts,v2, secondary visual cortex,vo, ventral orbitofrontal cortex,amygdala,neuroanatomy,rostral–caudal,rodent,submedius nucleus,thalamus
                Neurosciences
                a24b, anterior cingulate cortex, area 24b, ai, d, v, p, agranular insular cortex, dorsal, ventral, posterior parts, alo, lateral orbitofrontal cortex, anterior part, au1, auditory cortex, primary area, avo, ventral orbitofrontal cortex, anterior part, bla, basolateral nucleus of amygdala, blp, basolateral nucleus of the amygdala, posterior part, dlo, dorsolateral orbitofrontal cortex, gi, granular insular cortex, il, infralimbic cortex, ladl, lateral amygdala, dorsolateral part, lavl, lateral amygdala, ventrolateral part, lavm, lateral amygdala, ventromedial part, lent, lateral entorhinal cortex, lo, lateral orbitofrontal cortex, m1, primary motor cortex, m2, secondary motor cortex, md, m, c, l, mediodorsal nucleus of the thalamus, medial, central, lateral parts, mo, medial orbitofrontal cortex, pir, piriform cortex, pl, prelimbic cortex, plo, lateral orbitofrontal cortex, posterior part, prh, perirhinal cortex, pt, paratenial nucleus of the thalamus, pvo, ventral orbitofrontal cortex, posterior part, re, nucleus reuniens of the thalamus, rs, retrosplenial cortex, s1bf, primary somatosensory cortex, barrel field, s1j, primary somatosensory cortex, jaw region, s1hl/fl, primary somatosensory cortex, hindlimb and forelimb regions, s1tr, primary somatosensory cortex, trunk region, s2, secondary somatosensory cortex, sub, d, v, submedius nucleus of the thalamus, dorsal, ventral parts, v2, secondary visual cortex, vo, ventral orbitofrontal cortex, amygdala, neuroanatomy, rostral–caudal, rodent, submedius nucleus, thalamus

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