The long term objectives of the proposed research are to understand the role of the earliest born neurons in histogenesis of the cerebral cortex. The hypotheses that the earliest born neurons are unique, that they play a role in establishment of cortical connectivity, and that they are involved in establishment of differences among cortical areas will be tested Development of normal cortical function requires proper development of neuronal connectivity and transmitter expression. Interference with the normal sequence of events during any phase of cortical development can result in behavioral and cognitive disabilities ranging from subtle to severe. The proposed studies will focus on the earliest born neurons of the cerebral cortex. The timing and rate of neuron death in the earliest born neurons will be compared with the timing and rate of neuron death in two later born populations. The neurotransmitter and/or neuropeptide expressed by the earliest born neurons which die and those which survive will be examined to determine whether and when specific neuronal populations are selectively eliminated. To determine whether the earliest born neurons may be involved in specification of cortical areas, developmental patterns of expression of neuropeptides in 5 well-defined cortical areas will be compared. The population of neurons which participate in the initial formation of the callosal pathway will be identified, and the potential role of particular neurotransmitters or neuropeptides in growth cone guidance and axon branching will be assessed. The timing and extent of exuberance in the supragranular and infragranular callosal cells will be examined to determine whether or not axon withdrawal occurs in the neurons which pioneer the callosal pathway. Experiments will be done to determine whether or not callosal axons reach the contralateral hemisphere before their parent cell bodies complete migration, and whether not the neurons which send out the first callosal axons subsequently die.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038399-09
Application #
2244633
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1987-12-01
Project End
1996-08-31
Budget Start
1992-09-30
Budget End
1993-08-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Kansas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Sheffield, L G; Berman, N E (1998) Microglial expression of MHC class II increases in normal aging of nonhuman primates. Neurobiol Aging 19:47-55
Hausmann, E H; Berman, N E; Wang, Y Y et al. (1998) Selective chemokine mRNA expression following brain injury. Brain Res 788:49-59
Berman, N E; Johnson, J K; Klein, R M (1997) Early generation of glia in the intermediate zone of the developing cerebral cortex. Brain Res Dev Brain Res 101:149-64
Johnson, J K; Berman, N E (1996) A transient phase of cell death in the developing medial forebrain of the perinatal ferret. Brain Res Dev Brain Res 94:159-65
Choudhuri, S; Liu, W L; Berman, N E et al. (1996) Cadmium accumulation and metallothionein expression in brain of mice at different stages of development. Toxicol Lett 84:127-33
Grant, S; Berman, N E (1995) Late loss of connections during callosal development in Siamese cats. Brain Res Dev Brain Res 88:132-47
Sellner, P A; Chu, W; Glatz, J F et al. (1995) Developmental role of fatty acid-binding proteins in mouse brain. Brain Res Dev Brain Res 89:33-46
Hogan, D; Berman, N E (1994) The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas. Brain Res Dev Brain Res 77:1-21
McKenzie, J C; Berman, N E; Thomas, C R et al. (1994) Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex. Glia 12:228-43
Burns, T M; Clough, J A; Klein, R M et al. (1993) Developmental regulation of cytokine expression in the mouse brain. Growth Factors 9:253-8

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