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Mesocortical Dopamine Phenotypes in Mice Lacking the Sonic Hedgehog Receptor Cdon
- Source :
- eNeuro
- Publication Year :
- 2016
- Publisher :
- Society for Neuroscience, 2016.
-
Abstract
- Motivated behaviors and many psychopathologies typically involve changes in dopamine release from the projections of the ventral tegmental area (VTA) and/or the substantia nigra pars compacta (SNc). The morphogen Sonic Hedgehog (Shh) specifies fates of midbrain dopamine neurons, but VTA-specific effects of Shh signaling are also being uncovered. In this study, we assessed the role of the Shh receptor Cdon in the development of VTA and SNc dopamine neurons. We find that Cdon is expressed in the proliferating progenitor zone of the embryonic ventral midbrain and that the number of proliferating cells in this region is increased in mouseCdon−/−embryos. Consistent with a role of Shh in the regulation of neuronal proliferation in this region, we find that the number of tyrosine hydroxylase (TH)-positive neurons is increased in the VTA ofCdon−/−mice at birth and that this effect endures into adulthood. In contrast, the number of TH-positive neurons in the SNc is not altered inCdon−/−mice at either age. Moreover, adultCdon−/−mice have a greater number of medial prefrontal cortex (mPFC) dopamine presynaptic sites, and increased baseline concentrations of dopamine and dopamine metabolites selectively in this region. Finally, consistent with increased dopamine function in the mPFC, we find that adultCdon−/−mice fail to exhibit behavioral plasticity upon repeated amphetamine treatment. Based on these data, we suggest that Cdon plays an important role encoding the diversity of dopamine neurons in the midbrain, influencing both the development of the mesocortical dopamine pathway and behavioral outputs that involve this neural circuitry.
- Subjects :
- Male
Tyrosine 3-Monooxygenase
Dopamine
Neurogenesis
ventral tegmental area
Prefrontal Cortex
Substantia nigra
Motor Activity
Midbrain
sonic hedgehog
03 medical and health sciences
0302 clinical medicine
Neural Stem Cells
medicine
Cdon
Animals
Sonic hedgehog
Amphetamine
Pars Compacta
030304 developmental biology
Mice, Knockout
0303 health sciences
Tyrosine hydroxylase
biology
Pars compacta
Dopaminergic Neurons
General Neuroscience
General Medicine
New Research
Sensory Gating
Mice, Inbred C57BL
Ventral tegmental area
Phenotype
medicine.anatomical_structure
Cognition and Behavior
Animals, Newborn
nervous system
biology.protein
Central Nervous System Stimulants
Female
Cell Adhesion Molecules
Neuroscience
medial prefrontal cortex
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 23732822
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- eneuro
- Accession number :
- edsair.doi.dedup.....9bc1929bc578b5b117499dd2976ceb74