Organization of the Anterior Limb of the Internal Capsule in the Rat.
Dysfunction of the orbitofrontal (OFC) and anterior cingulate (ACC) cortices has been linked with several psychiatric disorders, including obsessive-compulsive disorder, major depressive disorder, posttraumatic stress disorder, and addiction. These conditions are also associated with abnormalities in the anterior limb of the internal capsule, the white matter (WM) bundle carrying ascending and descending fibers from the OFC and ACC. Furthermore, deep-brain stimulation (DBS) for psychiatric disorders targets these fibers. Experiments in rats provide essential information on the mechanisms of normal and abnormal brain anatomy, including WM composition and perturbations. However, whereas descending prefrontal cortex (PFC) fibers in primates form a well defined and topographic anterior limb of the internal capsule, the specific locations and organization of these fibers in rats is unknown. We address this gap by analyzing descending fibers from injections of an anterograde tracer in the rat ACC and OFC. Our results show that the descending PFC fibers in the rat form WM fascicles embedded within the striatum. These bundles are arranged topographically and contain projections, not only to the striatum, but also to the thalamus and brainstem. They can therefore be viewed as the rat homolog of the primate anterior limb of the internal capsule. Furthermore, mapping these projections allows us to identify the fibers likely to be affected by experimental manipulations of the striatum and the anterior limb of the internal capsule. These results are therefore essential for translating abnormalities of human WM and effects of DBS to rodent models.SIGNIFICANCE STATEMENTPsychiatric diseases are linked to abnormalities in specific white matter (WM) pathways, and the efficacy of deep-brain stimulation relies upon activation of WM. Experiments in rodents are necessary for studying the mechanisms of brain function. However, the translation of results between primates and rodents is hindered by the fact that the organization of descending WM in rodents is poorly understood. This is especially relevant for the prefrontal cortex, abnormal connectivity of which is central to psychiatric disorders. We address this gap by studying the organization of descending rodent prefrontal pathways. These fibers course through a subcortical structure, the striatum, and share important organization principles with primate WM. These results allow us to model primate WM effectively in the rodent.
INSERM, U1216, F-38000 Grenoble, France.|University of Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
Veronique
V
Coizet
Department of Pharmacology and Physiology, School of Medicine, University of Rochester, Rochester, New York 14642.
Sarah R
SR
Heilbronner
INSERM, U1216, F-38000 Grenoble, France.|University of Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
Carole
C
Carcenac
INSERM UMR 952, Centre National de Recherche Scientifique UMR 7224, Université Pierre et Marie Curie, Paris Cedex 05, France.
Philippe
P
Mailly
Department of Pharmacology and Physiology, School of Medicine, University of Rochester, Rochester, New York 14642.
Julia F
JF
Lehman
INSERM, U1216, F-38000 Grenoble, France.|University of Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
Marc
M
Savasta
INSERM, U1216, F-38000 Grenoble, France.|University of Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
Oivier
O
David
INSERM U667, Collège de France, 75 231 Paris Cedex 05, France, and.
Jean-Michel
JM
Deniau
Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Henk J
HJ
Groenewegen
Department of Pharmacology and Physiology, School of Medicine, University of Rochester, Rochester, New York 14642, suzanne_haber@urmc.rochester.edu.
Suzanne N
SN
Haber
D000818:Animals; D063132:Connectome / Q000379:methods*; D006179:Gyrus Cinguli / Q000166:cytology*; D020772:Internal Capsule / Q000166:cytology*; D008297:Male; D017397:Prefrontal Cortex / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
cingulate; deep-brain stimulation; homology; orbitofrontal; prefrontal cortex; white matter