The crossed mesostriatal projection: neurochemistry and developmental response to lesion

Anthony Altar, Kim A. Neve, Sandra E. Loughlin, John F. Marshall, James H. Fallon

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


The projections of substantia nigra and ventral tegmental area (SN-VTA) neurons to either the ipsilateral or contralateral caudate-putamen (CP) were studied in intact and 6-hydroxydopamine-treated rats, using both retrograde transport of fluorescent dyes and measurements of dopamine concentration. After unilateral CP injections of nuclear yellow or granular blue in intact 6- or 30-day-old rats, approximately 1% of the retrogradely labeled cells were located in the contralateral SN-VTA. In 6- or 30-day-old rats which had been injected with 6-hydroxydopamine in the left lateral hypothalamic area (LHA) at 1 day of age, the extent of cell labeling of both the uncrossed projection in the right hemisphere and the crossed projection originating in the left SN-VTA was normal. However, the number of labeled cells of the uncrossed pathway of the left side and the crossed pathway originating in the right SN-VTA were markedly decreased by the lesion, indicating that the crossed nigrostriatal cells decussate before they reach the LHA. The 6-hydroxydopamine-induced decreases in SN-VTA labeling of both the crossed and uncrossed pathway closely matched the degree of dopamine depletion in the lesioned CP at 6 days of age and at 30 days of age. A partial recovery of both measures occurred between days 6 and 30. Thus, retrograde labeling of SN-VTA cells with fluorescent dyes provided a quantitative measure of the dopaminergic innervation of the neostriatum in both the uncrossed and crossed pathways. The crossed mesostriatal cells are probably dopaminergic because: (1) they were as susceptible to the neurotoxic effects of 6-hydroxydopamine as the uncrossed dopamine cells; (2) they were located almost exclusively within the SN, pars compacta and VTA; and (3) their morphology resembled that of ipsilaterally projecting dopamine cells labeled with the same dye. Preliminary histofluorescence results also revealed that the crossed SN-VTA cells contained catecholamine.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBrain research
Issue number1-2
StatePublished - Nov 21 1983
Externally publishedYes


  • 6-hydroxydopamine
  • crossed mesostriatal projection
  • development
  • dopamine neurons
  • fluorescent dyes
  • neonatal brain lesion
  • retrograde labeling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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