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Live imaging of neuronal connections by magnetic resonance: Robust transport in the hippocampal–septal memory circuit in a mouse model of Down syndrome

Bearer, Elaine L. and Zhang, Xiaowei and Jacobs, Russell E. (2007) Live imaging of neuronal connections by magnetic resonance: Robust transport in the hippocampal–septal memory circuit in a mouse model of Down syndrome. NeuroImage, 37 (1). pp. 230-242. ISSN 1053-8119. PMCID PMC2074885. https://resolver.caltech.edu/CaltechAUTHORS:20160129-080803670

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[img] Video (MPEG) (Supplementary Movie 1. Video depicting SPM of 0.5 hr versus pre-injection data for the 2N littermate control group. The map shows the red ovoid cluster of Mn^(2+) enhanced voxels at the injection site in the hippocampus) - Supplemental Material
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[img] Video (MPEG) (Supplementary Movie 2. Video depicting SPM of 0.5 hr versus pre-injection data for Ts65Dn group. The map shows blue the ovoid cluster of Mn^(2+) enhanced voxels at the injection site in the hippocampus) - Supplemental Material
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[img] Video (MPEG) (Supplementary Movie 3. Video depicting SPM of 6 hr versus 0.5 hr post-injection data for the 2N littermate control group. At 6 hr post Mn^(2+) injection, enhanced voxels (red) depict the expected pathway from hippocampus, along the fimbria, ...) - Supplemental Material
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[img] Video (MPEG) (Supplementary Movie 4. Video depicting SPM of 6 hr versus 0.5 hr post-injection data for the Ts65DN group. At 6 hr post Mn^(2+) injection, enhanced voxels (blue) depict the expected pathway from hippocampus, along the fimbria, to the septal nuclei) - Supplemental Material
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[img] Video (MPEG) ( Supplementary Movie 5. Video depicting SPM of 24 hr versus 6 hr post-injection data for the 2N littermate control group. Mn^(2+) transport (red voxels) continues along known pathways from 6 to 24 hours with increased intensity in the septal regions, ...) - Supplemental Material
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[img] Video (MPEG) (Supplementary Movie 6. Video depicting SPM of 24 hr versus 6 hr post-injection data for Ts65DN group. Mn^(2+) transport (blue voxels) continues along known pathways from 6 to 24 hours with increased intensity in the septal regions, ...) - Supplemental Material
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Abstract

Connections from hippocampus to septal nuclei have been implicated in memory loss and the cognitive impairment in Down syndrome (DS). We trace these connections in living mice by Mn^(2+) enhanced 3D MRI and compare normal with a trisomic mouse model of DS, Ts65Dn. After injection of 4 nl of 200 mM Mn^(2+) into the right hippocampus, Mn^(2+) enhanced circuitry was imaged at 0.5, 6, and 24 h in each of 13 different mice by high resolution MRI to detect dynamic changes in signal over time. The pattern of Mn^(2+) enhanced signal in vivo correlated with the histologic pattern in fixed brains of co-injected 3kD rhodamine–dextran–amine, a classic tracer. Statistical parametric mapping comparing intensity changes between different time points revealed that the dynamics of Mn2+ transport in this pathway were surprisingly more robust in DS mice than in littermate controls, with statistically significant intensity changes in DS appearing at earlier time points along expected pathways. This supports reciprocal alterations of transport in the hippocampal-forebrain circuit as being implicated in DS and argues against a general failure of transport. This is the first examination of in vivo transport dynamics in this pathway and the first report of elevated transport in DS.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuroimage.2007.05.010DOIArticle
http://www.sciencedirect.com/science/article/pii/S1053811907004120PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074885/PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2007 Elsevier Inc. Received 8 February 2007; revised 11 April 2007; accepted 2 May 2007. Available online 18 May 2007. We thank Muriel Davisson and Cecilia Schmidt for their advice and help in obtaining and genotyping aged Ts65Dn mice and 2N littermates, to J.D. DelCroix for advice on hippocampal injections, and to the Moore Foundation for the Moore Distinguished Scholar award that brought E.L.B. to Caltech to collaborate in this work. The project was in part funded by NINDS NS046810, NIGMS GM47368 (E.L.B.), NCRR U24 RR021760 entitled Mouse BIRN and NIDA R01DA018184 (R.E.J.).
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
CaltechUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)NS046810
NIHGM47368
National Center for Research Resources (NCRR)U24 RR021760
National Institute on Drug Abuse (NIDA)R01DA018184
Subject Keywords:Axonal transport; Down syndrome; MRI; Tract tracing; Hippocampal-forebrain connection; Cholinergic neurons
Issue or Number:1
PubMed Central ID:PMC2074885
Record Number:CaltechAUTHORS:20160129-080803670
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160129-080803670
Official Citation:Elaine L. Bearer, Xiaowei Zhang, Russell E. Jacobs, Live imaging of neuronal connections by magnetic resonance: Robust transport in the hippocampal–septal memory circuit in a mouse model of Down syndrome, NeuroImage, Volume 37, Issue 1, 1 August 2007, Pages 230-242, ISSN 1053-8119, http://dx.doi.org/10.1016/j.neuroimage.2007.05.010. (http://www.sciencedirect.com/science/article/pii/S1053811907004120)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64078
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:29 Jan 2016 20:07
Last Modified:03 Oct 2019 09:34

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