The goal of this research is to elucidate fundamental principles governing the development of the visual system in primates including humans. Work on embryonic and fetal eye and visual brain centers directly in nonhuman primates is essential for the understanding of normal and pathological development of the visual system in man. The project consists of three integral parts conducted simultaneously: (1) normal prenatal development in rhesus monkey, (2) experimentally perturbed development in the monkey, and (3) correlation of development in monkey and human. In the first part, emphasis is on the mechanisms of neuronal genesis, migration, determination and differentiation including axonal growth and synaptogenesis in the retina, subcortical visual centers and visual cortex. In the second part, the consequences of selective destruction of visual centers and/or pathways sustained prenatally are evaluated in postnatal monkeys to determine the extent of neuronal plasticity and synaptic reorganization. Finally, in order to relate experimental data from nonhuman primates to man, we are performing correlative cytological analysis in both species using Golgi histochemistry and electron microscopy. The experimental analysis is conducted with a battery of modern neurological methods including 3H-thymidine autoradiography, Golgi impregnation, immunocytochemistry, electron microscopy, and retrograde, anterograde and transneuronal retrograde transport methods for tracing development of neuronal pathways. We have refined a prenatal neurosurgical procedure so that destruction and/or injection of radioactive tracers into selected brain regions during intrauterine life from the 50th day of pregnancy to birth is compatible with survival of fetus. Studies conducted this year include time of origin and cytology of interstitial neurons situated in the white matter subjacent to primary visual cortex, development of the superior colliculus, and genesis of afferent and efferent connections of the visual cortex in a series of fetal and postnatal monkeys.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002593-08
Application #
3256905
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1978-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
Hashimoto-Torii, Kazue; Sasaki, Masanori; Chang, Yu-Wen et al. (2018) Detection of local and remote cellular damage caused by spinal cord and peripheral nerve injury using a heat shock signaling reporter system. IBRO Rep 5:91-98
Rash, Brian G; Micali, Nicola; Huttner, Anita J et al. (2018) Metabolic regulation and glucose sensitivity of cortical radial glial cells. Proc Natl Acad Sci U S A 115:10142-10147
Morozov, Yury M; Koch, Marco; Rakic, Pasko et al. (2017) Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. Mol Metab 6:374-381
Torii, Masaaki; Sasaki, Masanori; Chang, Yu-Wen et al. (2017) Detection of vulnerable neurons damaged by environmental insults in utero. Proc Natl Acad Sci U S A 114:2367-2372
Morozov, Yury M; Sun, Yu-Yo; Kuan, Chia-Yi et al. (2016) Alteration of SLP2-like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain. Eur J Neurosci 43:245-57
Rash, Brian G; Ackman, James B; Rakic, Pasko (2016) Bidirectional radial Ca(2+) activity regulates neurogenesis and migration during early cortical column formation. Sci Adv 2:e1501733
Duque, Alvaro; Krsnik, Zeljka; Kostovi?, Ivica et al. (2016) Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates. Proc Natl Acad Sci U S A 113:9892-7
Benoit, Jamie; Ayoub, Albert; Rakic, Pasko (2016) Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation. Brain Struct Funct 221:3963-3978
Benoit, Jamie; Ayoub, Albert E; Rakic, Pasko (2015) Transcriptomics of critical period of visual cortical plasticity in mice. Proc Natl Acad Sci U S A 112:8094-9
Ayoub, Albert E; Rakic, Pasko (2015) Neuronal misplacement in schizophrenia. Biol Psychiatry 77:925-6

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