Projections of the medial orbital and ventral orbital cortex in the rat

The medial orbital (MO) and ventral orbital (VO) cortices are prominent divisions of the orbitomedial prefrontal cortex. To our knowledge, no previous report in the rat has comprehensively described the projections of MO and VO. By using the anterograde tracer Phaseolus vulgaris leucoagglutinin and the retrograde tracer Fluoro‐Gold, we examined the efferent projections of MO and VO in the rat. Although MO and VO projections overlap, MO distributes more widely throughout the brain, particularly to limbic structures, than does VO. The main cortical targets of MO were the orbital, ventral medial prefrontal (mPFC), agranular insular, piriform, retrosplenial, and parahippocampal cortices. The main subcortical targets of MO were the medial striatum, olfactory tubercle, claustrum, nucleus accumbens, septum, substantia innominata, lateral preoptic area, and diagonal band nuclei of the basal forebrain; central, medial, cortical, and basal nuclei of amygdala; paratenial, mediodorsal, and reuniens nuclei of the thalamus; posterior, supramammillary, and lateral nuclei of the hypothalamus; and periaqueductal gray, ventral tegmental area, substantia nigra, dorsal and median raphe, laterodorsal tegmental, and incertus nuclei of the brainstem. By comparison, VO distributes to some of these same sites, notably to the striatum, but lacks projections to parts of limbic cortex, to nucleus accumbens, and to the amygdala. VO distributes much more strongly, however, than MO to the medial (frontal) agranular, anterior cingulate, sensorimotor, posterior parietal, lateral agranular retrosplenial, and temporal association cortices. The patterns of MO projections are similar to those of the mPFC, whereas the projections of VO overlap with those of the ventrolateral orbital cortex (VLO). This suggests that MO serves functions comparable to those of the mPFC, such as goal‐directed behavior, and VO performs functions similar to VLO such as directed attention. MO/VO may also serve as a link between lateral orbital and medial prefrontal cortices. J. Comp. Neurol. 519:3766–3801, 2011. © 2011 Wiley‐Liss, Inc.

[1]  G Mann,et al.  ON THE THALAMUS * , 1905, British medical journal.

[2]  C. Leonard,et al.  The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. , 1969, Brain research.

[3]  J. Price,et al.  The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat , 1977, The Journal of comparative neurology.

[4]  M. Herkenham The connections of the nucleus reuniens thalami: Evidence for a direct thalamo‐hippocampal pathway in the rat , 1978, The Journal of comparative neurology.

[5]  O. Phillipson Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: A horseradish peroxidase study in the rat , 1979, The Journal of comparative neurology.

[6]  C. Saper,et al.  Convergence of autonomic and limbic connections in the insular cortex of the rat , 1982, The Journal of comparative neurology.

[7]  A. Craig,et al.  The thalamo‐cortical projection of the nucleus submedius in the cat , 1982, The Journal of comparative neurology.

[8]  R. L. Reep,et al.  Efferent connections of dorsal and ventral agranular insular cortex in the hamster, Mesocricetus auratus , 1982, Neuroscience.

[9]  R. Reep,et al.  Afferent connections of dorsal and ventral agranular insular cortex in the hamsterMesocricetus auratus , 1982, Neuroscience.

[10]  A. Beitz The organization of afferent projections to the midbrain periaqueductal gray of the rat , 1982, Neuroscience.

[11]  J. Marchand,et al.  Afferents to the periaqueductal gray in the rat. A horseradish peroxidase study , 1983, Neuroscience.

[12]  Atsutaka Hashimoto,et al.  Afferent connections of medial precentral cortex in the rat , 1984, Neuroscience Letters.

[13]  H. Fibiger,et al.  Cholinergic neurons of the laterodorsal tegmental nucleus: Efferent and afferent connections , 1986, The Journal of comparative neurology.

[14]  M. Cassell,et al.  Topography of projections from the medial prefrontal cortex to the amygdala in the rat , 1986, Brain Research Bulletin.

[15]  E. Neafsey,et al.  The topographical organization of neurons in the rat medial frontal, insular and olfactory cortex projecting to the solitary nucleus, olfactory bulb, periaqueductal gray and superior colliculus , 1986, Brain Research.

[16]  S. Hardy Projections to the midbrain from the medial versus lateral prefrontal cortices of the rat , 1986, Neuroscience Letters.

[17]  H. Groenewegen Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography , 1988, Neuroscience.

[18]  R. Roth,et al.  Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract‐tracing study with Phaseolus vulgaris leucoagglutinin , 1989, The Journal of comparative neurology.

[19]  M. A. Siegel,et al.  Collateralization of the amygdaloid projections of the rat prelimbic and infralimbic cortices , 1989, The Journal of comparative neurology.

[20]  M. Marcinkiewicz,et al.  CNS connections with the median raphe nucleus: Retrograde tracing with WGA‐apoHRP‐gold complex in the rat , 1989, The Journal of comparative neurology.

[21]  Sheng Chen,et al.  Afferent connections of the thalamic paraventricular and parataenial nuclei in the rat — a retrograde tracing study with iontophoretic application of Fluoro-Gold , 1990, Brain Research.

[22]  H. Uylings,et al.  Qualitative and quantitative comparison of the prefrontal cortex in rat and in primates, including humans. , 1990, Progress in brain research.

[23]  M. Witter,et al.  Projection from the nucleus reuniens thalami to the hippocampal region: Light and electron microscopic tracing study in the rat with the anterograde tracer Phaseolus vulgaris‐leucoagglutinin , 1990, The Journal of comparative neurology.

[24]  Françoise Condé,et al.  Afferent connections of the medial frontal cortex of the rat. A study using retrograde transport of fluorescent dyes. I. Thalamic afferents , 1990, Brain Research Bulletin.

[25]  H. Groenewegen,et al.  The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. , 1990, Progress in brain research.

[26]  L. Wiklund,et al.  Afferents to the median raphe nucleus of the rat: Retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selectived-[3H]aspartate labelling of possible excitatory amino acid inputs , 1990, Neuroscience.

[27]  R. Reep,et al.  Topographic organization in the corticocortical connections of medial agranular cortex in rats , 1990, The Journal of comparative neurology.

[28]  L. Hersh,et al.  Prefrontal cortical projections to the cholinergic neurons in the basal forebrain , 1991, The Journal of comparative neurology.

[29]  H. Groenewegen,et al.  Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat , 1991, Neuroscience.

[30]  F. Wouterlood,et al.  Innervation of Entorhinal Principal Cells by Neurons of the Nucleus Reuniens Thalami. Anterograde PHA‐L Tracing Combined with Retrograde Fluorescent Tracing and Intracellular Injection with Lucifer Yellow in the Rat , 1991, The European journal of neuroscience.

[31]  Tanemichi Chiba,et al.  Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study , 1991, Brain Research.

[32]  M. T. Shipley,et al.  Topographical Specificity of Forebrain Inputs to the Midbrain Periaqueductal Gray: Evidence for Discrete Longitudinally Organized Input Columns , 1991 .

[33]  C. Saper,et al.  Efferent projections of the infralimbic cortex of the rat , 1991, The Journal of comparative neurology.

[34]  S. Sesack,et al.  Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area , 1992, The Journal of comparative neurology.

[35]  J. Price,et al.  The organization of the thalamocortical connections of the mediodorsal thalamic nucleus in the rat, related to the ventral forebrain–prefrontal cortex topography , 1992, The Journal of comparative neurology.

[36]  H. Groenewegen,et al.  Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat , 1992, The Journal of comparative neurology.

[37]  Larry W. Swanson,et al.  Brain Maps: Structure of the Rat Brain , 1992 .

[38]  K. Bowen,et al.  Retrograde tracing of projections between the nucleus submedius, the ventrolateral orbital cortex, and the midbrain in the rat , 1992, The Journal of comparative neurology.

[39]  J. Dostrovsky,et al.  The afferent and efferent connections of the nucleus submedius in the rat , 1992, The Journal of comparative neurology.

[40]  D. S. Zahm,et al.  The patterns of afferent innervation of the core and shell in the “Accumbens” part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro‐gold , 1993, The Journal of comparative neurology.

[41]  R. Reep,et al.  Bilateral destruction of the ventrolateral orbital cortex produces allocentric but not egocentric spatial deficits in rats , 1994, Behavioural Brain Research.

[42]  E. Audinat,et al.  Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents , 1995, The Journal of comparative neurology.

[43]  L. Swanson,et al.  Evidence for a hypothalamothalamocortical circuit mediating pheromonal influences on eye and head movements. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. Deniau,et al.  Prefrontal cortex inputs of the nucleus accumbens-nigro-thalamic circuit , 1996, Neuroscience.

[45]  F. Mascagni,et al.  Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat , 1996, Neuroscience.

[46]  M P Witter,et al.  Projections from the nucleus reuniens thalami to the entorhinal cortex, hippocampal field CA1, and the subiculum in the rat arise from different populations of neurons , 1996, The Journal of comparative neurology.

[47]  L. Swanson,et al.  The structural organization of connections between hypothalamus and cerebral cortex 1 Published on the World Wide Web on 2 June 1997. 1 , 1997, Brain Research Reviews.

[48]  C. Rampon,et al.  Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods , 1997, Neuroscience.

[49]  M. Hajós,et al.  An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat , 1998, Neuroscience.

[50]  A. McDonald Cortical pathways to the mammalian amygdala , 1998, Progress in Neurobiology.

[51]  R. Reep,et al.  Rodent posterior parietal cortex as a component of a cortical network mediating directed spatial attention , 1998, Psychobiology.

[52]  R. Llinás,et al.  The neuronal basis for consciousness. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[53]  Charles R. Yang,et al.  Medial prefrontal cortical output neurons to the ventral tegmental area (VTA) and their responses to burst‐patterned stimulation of the VTA: Neuroanatomical and in vivo electrophysiological analyses , 1999, Synapse.

[54]  H. Groenewegen,et al.  Integration and segregation of limbic cortico-striatal loops at the thalamic level: an experimental tracing study in rats , 1999, Journal of Chemical Neuroanatomy.

[55]  R P Kesner,et al.  Involvement of rodent prefrontal cortex subregions in strategy switching. , 1999, Behavioral neuroscience.

[56]  R. Reep,et al.  Topographic organization of the striatal and thalamic connections of rat medial agranular cortex , 1999, Brain Research.

[57]  S Laroche,et al.  Plasticity at hippocampal to prefrontal cortex synapses: Dual roles in working memory and consolidation , 2000, Hippocampus.

[58]  R Bandler,et al.  Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat , 2000, The Journal of comparative neurology.

[59]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[60]  V. Brown,et al.  Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat , 2000, The Journal of Neuroscience.

[61]  S. Sesack,et al.  Projections from the Rat Prefrontal Cortex to the Ventral Tegmental Area: Target Specificity in the Synaptic Associations with Mesoaccumbens and Mesocortical Neurons , 2000, The Journal of Neuroscience.

[62]  L W Swanson,et al.  Connections of the nucleus incertus , 2001, The Journal of comparative neurology.

[63]  M. E. Corcoran,et al.  Susceptibility to Kindling and Neuronal Connections of the Anterior Claustrum , 2001, The Journal of Neuroscience.

[64]  R Bandler,et al.  Orbitomedial prefrontal cortical projections to hypothalamus in the rat , 2001, The Journal of comparative neurology.

[65]  M. Witter,et al.  The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness , 2002, Brain Research Reviews.

[66]  H. Bokor,et al.  Cellular architecture of the nucleus reuniens thalami and its putative aspartatergic/glutamatergic projection to the hippocampus and medial septum in the rat , 2002, The European journal of neuroscience.

[67]  R. Vertes,et al.  Analysis of projections from the medial prefrontal cortex to the thalamus in the rat, with emphasis on nucleus reuniens , 2002, The Journal of comparative neurology.

[68]  R. Reep,et al.  The associative striatum: Organization of cortical projections to the dorsocentral striatum in rats , 2003, The Journal of comparative neurology.

[69]  T. Robbins,et al.  Dissociable Contributions of the Orbitofrontal and Infralimbic Cortex to Pavlovian Autoshaping and Discrimination Reversal Learning: Further Evidence for the Functional Heterogeneity of the Rodent Frontal Cortex , 2003, The Journal of Neuroscience.

[70]  B. Waterhouse,et al.  Glutamatergic afferent projections to the dorsal raphe nucleus of the rat , 2003, Brain Research.

[71]  V. Brown,et al.  Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat , 2003, Behavioural Brain Research.

[72]  M. Ragozzino,et al.  The contribution of the rat prelimbic-infralimbic areas to different forms of task switching. , 2003, Behavioral neuroscience.

[73]  B. Balleine,et al.  The role of prelimbic cortex in instrumental conditioning , 2003, Behavioural Brain Research.

[74]  R. L. Reep,et al.  Rat posterior parietal cortex: topography of corticocortical and thalamic connections , 2004, Experimental Brain Research.

[75]  L. Jasmin,et al.  Rostral agranular insular cortex and pain areas of the central nervous system: A tract‐tracing study in the rat , 2004, The Journal of comparative neurology.

[76]  T. Robbins,et al.  Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates , 2004, Neuroscience & Biobehavioral Reviews.

[77]  T. Robinson,et al.  Plasticity and functions of the orbital frontal cortex , 2004, Brain and Cognition.

[78]  D. Powell,et al.  Efferent connections of the medial prefrontal cortex in the rabbit , 1994, Experimental Brain Research.

[79]  R. Vertes,et al.  Afferent projections to nucleus reuniens of the thalamus , 2004, The Journal of comparative neurology.

[80]  R. Reep,et al.  Neuronal connections of orbital cortex in rats: topography of cortical and thalamic afferents , 1996, Experimental Brain Research.

[81]  S. Sesack,et al.  Prefrontal cortical projections to the rat dorsal raphe nucleus: Ultrastructural features and associations with serotonin and γ‐aminobutyric acid neurons , 2004, The Journal of comparative neurology.

[82]  R. Vertes Differential projections of the infralimbic and prelimbic cortex in the rat , 2004, Synapse.

[83]  S. Geisler,et al.  Afferents of the ventral tegmental area in the rat‐anatomical substratum for integrative functions , 2005, The Journal of comparative neurology.

[84]  M. Roesch,et al.  Orbitofrontal Cortex, Associative Learning, and Expectancies , 2005, Neuron.

[85]  Paul Leonard Gabbott,et al.  Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers , 2005, The Journal of comparative neurology.

[86]  B. Balleine,et al.  Lesions of Medial Prefrontal Cortex Disrupt the Acquisition But Not the Expression of Goal-Directed Learning , 2005, The Journal of Neuroscience.

[87]  Michael E. Ragozzino,et al.  The involvement of the orbitofrontal cortex in learning under changing task contingencies , 2005, Neurobiology of Learning and Memory.

[88]  D. S. Zahm,et al.  Specificity in the Projections of Prefrontal and Insular Cortex to Ventral Striatopallidum and the Extended Amygdala , 2005, The Journal of Neuroscience.

[89]  R. Reep,et al.  Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat , 2005, Brain Research.

[90]  R. Vertes,et al.  Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat , 2006, The Journal of comparative neurology.

[91]  Robert P. Vertes,et al.  Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat , 2006, Neuroscience.

[92]  Harry B. M. Uylings,et al.  The rat orbital and agranular insular prefrontal cortical areas: a cytoarchitectonic and chemoarchitectonic study , 2008, Brain Structure and Function.

[93]  R. Joosten,et al.  Medial prefrontal serotonin in the rat is involved in goal-directed behaviour when affect guides decision making , 2007, Psychopharmacology.

[94]  R. Vertes,et al.  Nucleus reuniens of the midline thalamus: Link between the medial prefrontal cortex and the hippocampus , 2007, Brain Research Bulletin.

[95]  B. Balleine,et al.  Orbitofrontal Cortex Mediates Outcome Encoding in Pavlovian But Not Instrumental Conditioning , 2007, The Journal of Neuroscience.

[96]  B. Balleine,et al.  The Contribution of Orbitofrontal Cortex to Action Selection , 2007, Annals of the New York Academy of Sciences.

[97]  G. Schoenbaum,et al.  Reconciling the Roles of Orbitofrontal Cortex in Reversal Learning and the Encoding of Outcome Expectancies , 2007, Annals of the New York Academy of Sciences.

[98]  J. Price Definition of the Orbital Cortex in Relation to Specific Connections with Limbic and Visceral Structures and Other Cortical Regions , 2007, Annals of the New York Academy of Sciences.

[99]  D. S. Zahm,et al.  Glutamatergic Afferents of the Ventral Tegmental Area in the Rat , 2007, The Journal of Neuroscience.

[100]  Tomoyuki Furuyashiki,et al.  Neural Encoding in the Orbitofrontal Cortex Related to Goal‐Directed Behavior , 2007, Annals of the New York Academy of Sciences.

[101]  J. O'Doherty,et al.  What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies , 2007, The Journal of Neuroscience.

[102]  R. Vertes,et al.  Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat , 2007, Brain Structure and Function.

[103]  Geoffrey Schoenbaum,et al.  Double Dissociation of the Effects of Medial and Orbital Prefrontal Cortical Lesions on Attentional and Affective Shifts in Mice , 2008, The Journal of Neuroscience.

[104]  H. Shibata,et al.  Organization of anterior cingulate and frontal cortical projections to the retrosplenial cortex in the rat , 2008, The Journal of comparative neurology.

[105]  Daphna Joel,et al.  The orbital cortex in rats topographically projects to central parts of the caudate–putamen complex , 2008, Neuroscience Letters.

[106]  R. Vertes,et al.  Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat , 2008, The Journal of comparative neurology.

[107]  B. Moghaddam,et al.  Orbitofrontal cortex neurons as a common target for classic and glutamatergic antipsychotic drugs , 2008, Proceedings of the National Academy of Sciences.

[108]  S. Sesack,et al.  Ultrastructural analysis of prefrontal cortical inputs to the rat amygdala: spatial relationships to presumed dopamine axons and D1 and D2 receptors , 2008, Brain Structure and Function.

[109]  R. Vertes,et al.  Efferent and afferent connections of the dorsal and median raphe nuclei in the rat , 2008 .

[110]  Tomoyuki Furuyashiki,et al.  Rat Orbitofrontal Cortex Separately Encodes Response and Outcome Information during Performance of Goal-Directed Behavior , 2008, The Journal of Neuroscience.

[111]  R. Reep,et al.  Posterior parietal cortex as part of a neural network for directed attention in rats , 2009, Neurobiology of Learning and Memory.

[112]  S. J. Shammah-Lagnado,et al.  Prefrontal afferents to the dorsal raphe nucleus in the rat , 2009, Brain Research Bulletin.

[113]  B. Moghaddam,et al.  Differential representation of Pavlovian–instrumental transfer by prefrontal cortex subregions and striatum , 2009, The European journal of neuroscience.

[114]  G. Schoenbaum,et al.  Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with ‘disinhibition’ of responding for previously unrewarded cues , 2009, The European journal of neuroscience.

[115]  M. Rushworth,et al.  General Mechanisms for Making Decisions? This Review Comes from a Themed Issue on Cognitive Neuroscience Edited the Representation of Value and Reward Expectations in Frontal Cortex Reward Prediction Errors and Learning Rates Other Types of Prediction Error , 2022 .

[116]  M. Roesch,et al.  The Orbitofrontal Cortex and Ventral Tegmental Area Are Necessary for Learning from Unexpected Outcomes , 2009, Neuron.

[117]  C. Qu,et al.  The thalamic nucleus submedius and ventrolateral orbital cortex are involved in nociceptive modulation: A novel pain modulation pathway , 2009, Progress in Neurobiology.

[118]  M. Roesch,et al.  A new perspective on the role of the orbitofrontal cortex in adaptive behaviour , 2009, Nature Reviews Neuroscience.

[119]  Guillem R. Esber,et al.  How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function , 2010, Current Opinion in Neurobiology.

[120]  Jung Hoon Sul,et al.  Distinct Roles of Rodent Orbitofrontal and Medial Prefrontal Cortex in Decision Making , 2010, Neuron.

[121]  N. Canteras,et al.  Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats , 2010, Neurobiology of Learning and Memory.