title: Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence.
abstract: The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Using optogenetic stimulation and in vivo two-photon imaging in adolescent mice, we found that phasic, but not tonic, dopamine neuron activity induces the formation of mesofrontal axonal boutons. In contrast, in adult mice, the effect of phasic activity diminishes. Furthermore, our results showed that dopaminergic and glutamatergic transmission regulate this axonal plasticity in adolescence and inhibition of dopamine D2-type receptors restores this plasticity in adulthood. Finally, we found that phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, and.
authors.forename: Surjeet
authors.initials: S
authors.lastname: Mastwal
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, and.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, and.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: Lieber Institute for Brain Development and.
authors.forename: Dennisse V
authors.initials: DV
authors.lastname: Jimenez
authors.affiliation: Lieber Institute for Brain Development and Departments of Psychiatry and Behavioral Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
authors.affiliation: Laboratory of Systems Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Gerfen
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, and wkuan@mail.nih.gov.
authors.forename: Kuan Hong
authors.initials: KH
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003911:Dextrans / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005625:Frontal Lobe / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D012235:Rhodamines / Q000493:pharmacokinetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000378:metabolism
chemical_list: D003911:Dextrans; D015259:Dopamine Agents; D018683:Excitatory Amino Acid Agents; C067661:Fluoro-Ruby; D012235:Rhodamines; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase
keywords: adolescence; dopamine; frontal cortex; in vivo imaging; optogenetics; phasic activity