Experiments are proposed to investigate the role of abnormal early experience in producing abnormal neural pathways linking the left and right hemispheres of the brain. The interhemispheric pathway matures quite late during development, and its pattern of development is particularly interesting. There is an initial over-production of connections (mistakes?) followed by a gradual narrowing of the zone containing neurons which send axons to the opposite hemisphere. This narrowing process can be altered when there is unusual experience, resulting in persistence of developmental mistakes, which could provide a substrate for abnormal behavior. We will use anatomical techniques involving retrograde transport of horseradish peroxidase and anterograde transport of isotope to address a number of questions related to the role of abnormal experience in producing abnormal interhemispheric pathways. We will use a model system chosen to allow complete control of early experience. In addition, the anatomy and physiology of the interhemispheric pathway are well understood in this system. The goal of the experiments is to increase our understanding of the link between abnormal early experience and abonormal behavior. It has been known for many years that abnormal experience in childhood can result in severe mental health problems in adulthood. Since abnormal experience can result in retention of developmental mistakes in brain connectivity, this link may form a structural basis of many psychiatric disorders. Interhemispheric pathways may be particularly vulnerable to abnormal early experience. Indeed, recent computed tomography studies of schizophrenic patients have shown that they have a high incidence of abnormal hemispheric specialization. The proposed experiments will explore the circumstances and mechanism for retention of developmental mistakes in interhemispheric connectivity resulting from abnormal early experience.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038399-03
Application #
3376695
Study Section
(BPNB)
Project Start
1983-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
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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