A DTI tractography analysis of infralimbic and prelimbic connectivity in the mouse using high-throughput MRI

BACKGROUND High throughput, brain-wide analysis of neural circuit connectivity is needed to understand brain function across species. Combining such tractography techniques with small animal models will allow more rapid integration of systems neuroscience with molecular genetic, behavioral, and cellular approaches. METHODS We collected DTI and T2 scans on 3 series of 6 fixed mouse brains ex vivo in a 9.4 Tesla magnet. The DTI analysis of ten mouse brains focused on comparing prelimbic (PL) and Infralimbic (IL) probabilistic tractography. To validate the DTI results a preliminary set of 24 additional mice were injected with BDA into the IL and PL. The DTI results and preliminary BDA results were also compared to previously published rat connectivity. RESULTS We focused our analyses on the connectivity of the mouse prelimbic (PL) vs. infralimbic (IL) cortices. We demonstrated that this DTI analysis is consistent across scanned mice, with prior analyses of rat IL/PL connectivity, and with mouse PL and IL projections using the BDA tracer. CONCLUSIONS High-throughput ex vivo DTI imaging in the mouse delineated both common and differential connectivity of the IL and PL cortex. The scanning methodology provided a balance of tissue contrast, signal-to-noise ratio, resolution and throughput. Our results are largely consistent with previously published anterograde staining techniques in rats, and the preliminary tracer study of the mouse IL and PL provided here.

[1]  R Mark Henkelman,et al.  Systems biology through mouse imaging centers: experience and new directions. , 2010, Annual review of biomedical engineering.

[2]  J. Schneider,et al.  Making the mouse embryo transparent: identifying developmental malformations using magnetic resonance imaging. , 2004, Birth defects research. Part C, Embryo today : reviews.

[3]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

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

[5]  Jacob Jelsing,et al.  Validation of in vitro probabilistic tractography , 2007, NeuroImage.

[6]  Hao Huang,et al.  Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging , 2003, NeuroImage.

[7]  Stephen M. Smith,et al.  DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease , 2011, NeuroImage.

[8]  Michael Davis,et al.  Mapping of the mouse olfactory system with manganese-enhanced magnetic resonance imaging and diffusion tensor imaging , 2013, Brain Structure and Function.

[9]  Timothy Edward John Behrens,et al.  A Tractography Analysis of Two Deep Brain Stimulation White Matter Targets for Depression , 2009, Biological Psychiatry.

[10]  G. Quirk,et al.  The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear , 2000, The Journal of Neuroscience.

[11]  S. Rauch,et al.  Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. , 2006, Learning & memory.

[12]  Carl-Fredrik Westin,et al.  3D Histological Reconstruction of Fiber Tracts and Direct Comparison with Diffusion Tensor MRI Tractography , 2006, MICCAI.

[13]  Alan Connelly,et al.  Super-resolution track-density imaging studies of mouse brain: Comparison to histology , 2012, NeuroImage.

[14]  R Mark Henkelman,et al.  MRI phenotyping of genetically altered mice. , 2011, Methods in molecular biology.

[15]  G. Quirk,et al.  Activity in Prelimbic Cortex Is Necessary for the Expression of Learned, But Not Innate, Fears , 2007, The Journal of Neuroscience.

[16]  R. LaLumiere,et al.  Neural circuit competition in cocaine‐seeking: roles of the infralimbic cortex and nucleus accumbens shell , 2012, The European journal of neuroscience.

[17]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[18]  J. Churchwell,et al.  Posttraining lesions of the medial prefrontal cortex impair performance of Pavlovian eyeblink conditioning but have no effect on concomitant heart rate changes in rabbits (Oryctolagus cuniculus). , 2001, Behavioral neuroscience.

[19]  C. Köhler,et al.  An immunohistochemical study of somatostatin and neurotensin positive neurons in the septal nuclei of the rat brain , 2004, Anatomy and Embryology.

[20]  Jeremy D. Schmahmann,et al.  Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers , 2008, NeuroImage.

[21]  J. Churchwell,et al.  Medial prefrontal cortex and pavlovian conditioning: trace versus delay conditioning. , 2002, Behavioral neuroscience.

[22]  Timothy E. J. Behrens,et al.  The evolution of the arcuate fasciculus revealed with comparative DTI , 2008, Nature Neuroscience.

[23]  Carl-Fredrik Westin,et al.  Comparison of fiber tracts derived from in-vivo DTI tractography with 3D histological neural tract tracer reconstruction on a macaque brain , 2007, NeuroImage.

[24]  P. Kalivas,et al.  Role of the prefrontal cortex and nucleus accumbens in reinstating methamphetamine seeking , 2010, The European journal of neuroscience.

[25]  A. Dale,et al.  Quantitative Histological Validation of Diffusion MRI Fiber Orientation Distributions in the Rat Brain , 2010, PloS one.

[26]  Peter C. Holland,et al.  Effects of dorsal or ventral medial prefrontal cortical lesions on five-choice serial reaction time performance in rats , 2011, Behavioural Brain Research.

[27]  G. Quirk,et al.  Neurons in medial prefrontal cortex signal memory for fear extinction , 2002, Nature.

[28]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[29]  Timothy E. J. Behrens,et al.  Just pretty pictures? What diffusion tractography can add in clinical neuroscience , 2006, Current opinion in neurology.

[30]  G. Quirk,et al.  Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. , 2004, Behavioral neuroscience.

[31]  Xiaoping Hu,et al.  Chimpanzee (Pan troglodytes) Precentral Corticospinal System Asymmetry and Handedness: A Diffusion Magnetic Resonance Imaging Study , 2010, PloS one.

[32]  W. Baaré,et al.  An ex vivo imaging pipeline for producing high‐quality and high‐resolution diffusion‐weighted imaging datasets , 2011, Human brain mapping.

[33]  Dennis C. Choi,et al.  Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear , 2010, Proceedings of the National Academy of Sciences.

[34]  I. L. Nieuwenhuis,et al.  The role of the ventromedial prefrontal cortex in memory consolidation , 2011, Behavioural Brain Research.

[35]  J. Peters,et al.  Infralimbic Prefrontal Cortex Is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats , 2008, The Journal of Neuroscience.

[36]  R. LaLumiere,et al.  The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration. , 2010, Learning & memory.