Dopamine Axon Targeting in the Nucleus Accumbens in Adolescence Requires Netrin-1.
adolescence
cortical development
dopamine innervation
guidance cues
nucleus accumbens
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
03
2020
accepted:
25
05
2020
entrez:
28
7
2020
pubmed:
28
7
2020
medline:
28
7
2020
Statut:
epublish
Résumé
The fine arrangement of neuronal connectivity during development involves the coordinated action of guidance cues and their receptors. In adolescence, the dopamine circuitry is still developing, with mesolimbic dopamine axons undergoing target-recognition events in the nucleus accumbens (NAcc), while mesocortical projections continue to grow toward the prefrontal cortex (PFC) until adulthood. This segregation of mesolimbic versus mesocortical dopamine pathways is mediated by the guidance cue receptor DCC, which signals dopamine axons intended to innervate the NAcc to recognize this region as their final target. Whether DCC-dependent mesolimbic dopamine axon targeting in adolescence requires the action of its ligand, Netrin-1, is unknown. Here we combined shRNA strategies, quantitative analysis of pre- and post-synaptic markers of neuronal connectivity, and pharmacological manipulations to address this question. Similar to DCC levels in the ventral tegmental area, Netrin-1 expression in the NAcc is dynamic across postnatal life, transitioning from high to low expression across adolescence. Silencing Netrin-1 in the NAcc in adolescence results in an increase in the expanse of the dopamine input to the PFC in adulthood, with a corresponding increase in the number of presynaptic dopamine sites. This manipulation also results in altered dendritic spine density and morphology of medium spiny neurons in the NAcc in adulthood and in reduced sensitivity to the behavioral activating effects of the stimulant drug of abuse, amphetamine. These cellular and behavioral effects mirror those induced by
Identifiants
pubmed: 32714924
doi: 10.3389/fcell.2020.00487
pmc: PMC7344302
doi:
Types de publication
Journal Article
Langues
eng
Pagination
487Subventions
Organisme : NIDA NIH HHS
ID : R01 DA037911
Pays : United States
Informations de copyright
Copyright © 2020 Cuesta, Nouel, Reynolds, Morgunova, Torres-Berrío, White, Hernandez, Cooper and Flores.
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