TY - JOUR
T1 - Development of a MR-Visible Compound for Tracing Neuroanatomical Connections In Vivo
AU - Wu, Carolyn W.H.
AU - Vasalatiy, Olga
AU - Liu, Ning
AU - Wu, Haitao
AU - Cheal, Sarah
AU - Chen, Der Yow
AU - Koretsky, Alan P.
AU - Griffiths, Gary L.
AU - Tootell, Roger B.H.
AU - Ungerleider, Leslie G.
N1 - Funding Information:
We are grateful to Steve Dodd for pulse sequence optimization, David Yu for brain slicing, and Kathy Sharer for animal ordering and care. This work was supported in part by the NIMH and NINDS IRP, NeuroSpin/CEA, the Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute, NIH grant R01 EY017081 to R.B.H.T., and the French L'Agence Nationale de la Recherche grant ANR-09-BLAN-0061-CSD8 to C.W.-H.W.
PY - 2011/4/28
Y1 - 2011/4/28
N2 - Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (S1) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.7T and 7T. The transported GdDOTA-CTB was visible for at least 1 month post-injection, clearing within 2 months. Control injections of non-conjugated GdDOTA into S1 were not transported and cleared within 1-2 days. Control injections of Gd-Albumin were not transported either, clearing within 7 days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.
AB - Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (S1) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.7T and 7T. The transported GdDOTA-CTB was visible for at least 1 month post-injection, clearing within 2 months. Control injections of non-conjugated GdDOTA into S1 were not transported and cleared within 1-2 days. Control injections of Gd-Albumin were not transported either, clearing within 7 days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.
UR - https://www.scopus.com/pages/publications/79955108718
UR - https://www.scopus.com/pages/publications/79955108718#tab=citedBy
U2 - 10.1016/j.neuron.2011.03.010
DO - 10.1016/j.neuron.2011.03.010
M3 - Article
C2 - 21521610
AN - SCOPUS:79955108718
SN - 0896-6273
VL - 70
SP - 229
EP - 243
JO - Neuron
JF - Neuron
IS - 2
ER -
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