The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry

Manitt, Colleen, Mimee, Andrea, Eng, Conrad, Pokinko, Matthew, Stroh, Thomas, Cooper, Helen M., Kolb, Bryan and Flores, Cecilia (2011) The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. The Journal of Neuroscience, 31 23: 8381-8394. doi:10.1523/JNEUROSCI.0606-11.2011

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Author Manitt, Colleen
Mimee, Andrea
Eng, Conrad
Pokinko, Matthew
Stroh, Thomas
Cooper, Helen M.
Kolb, Bryan
Flores, Cecilia
Title The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry
Journal name The Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2011-06-08
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.0606-11.2011
Open Access Status File (Publisher version)
Volume 31
Issue 23
Start page 8381
End page 8394
Total pages 14
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Collection year 2012
Language eng
Formatted abstract
Netrins are guidance cues involved in neural connectivity. We have shown that the netrin-1 receptor DCC (deleted in colorectal cancer) is involved in the functional organization of the mesocorticolimbic dopamine (DA) system. Adult mice with a heterozygous loss-of-function mutation in dcc exhibit changes in indexes of DA function, including DA-related behaviors. These phenotypes are only observed after puberty, a critical period in the maturation of the mesocortical DA projection. Here, we examined whether dcc heterozygous mice exhibit structural changes in medial prefrontal cortex (mPFC) DA synaptic connectivity, before and after puberty. Stereological counts of tyrosine-hydroxylase (TH)-positive varicosities were increased in the cingulate 1 and prelimbic regions of the pregenual mPFC. dcc heterozygous mice also exhibited alterations in the size, complexity, and dendritic spine density of mPFC layer V pyramidal neuron basilar dendritic arbors. Remarkably, these presynaptic and postsynaptic partner phenotypes were not observed in juvenile mice, suggesting that DCC selectively influences the extensive branching and synaptic differentiation that occurs in the maturing mPFC DA circuit at puberty. Immunolabeling experiments in wild-type mice demonstrated that DCC is segregated to TH-positive fibers innervating the nucleus accumbens, with only scarce DCC labeling in mPFC TH-positive fibers. Netrin had an inverted target expression pattern. Thus, DCC-mediated netrin-1 signaling may influence the formation/maintenance of mesocorticolimbic DA topography. In support of this, we report that dcc heterozygous mice exhibit a twofold increase in the density of mPFC DCC/TH-positive varicosities. Our results implicate DCC-mediated netrin-1 signaling in the establishment of mPFC DA circuitry during puberty.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 34 times in Scopus Article | Citations
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Created: Fri, 11 Nov 2011, 11:28:28 EST by Debra McMurtrie on behalf of Queensland Brain Institute