Recent studies indicate that zinc plays important neuromodulatory roles in the mammalian central nervous system. Specific populations of zinc-containing neurons are now known to be present in the brain, particularly in areas important for cognitive and emotional function. At this time however, little is known about the locations or efferent projections of these groups of neurons. The goal of the research proposed here is to map the principal zinc-containing pathways of the brain, using the rat as an experimental model. Zinc-containing neurons sequester zinc in the vesicles of their axon boutons. In the present work, the regional distribution of zinc-containing boutons will be determined by use of two complementary histochemical methods, neo-Timm's, which selectively labels metal-containing boutons, and quinoline fluorescence, which is a newly-developed specific marker for zinc. Quinoline histofluorometry will also be used to obtain quantitative estimates of the relative numbers of zinc-containing boutons in selected brain regions. The efferent pathways of the zinc-containing fiber systems will be studied by conventional lesion/degeneration methods, coupled with zinc-histochemistry to demonstrate the loss of zinc- containing boutons after fiber degeneration. To complement the degeneration studies in selected cases, retrograde axonal transport of labeled zinc ions will be used to locate cells of origin. The results will reveal the anatomical organization of some of the principal zinc-containing circuits in the brain, providing an empirical foundation for future theory and experimentation on these neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH042798-03
Application #
3382087
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas-Dallas
Department
Type
Other Specialized Schools
DUNS #
City
Richardson
State
TX
Country
United States
Zip Code
75080
Christensen, M K; Frederickson, C J (1998) Zinc-containing afferent projections to the rat corticomedial amygdaloid complex: a retrograde tracing study. J Comp Neurol 400:375-90
Long, Y; Hardwick, A L; Frederickson, C J (1995) Zinc-containing innervation of the subicular region in the rat. Neurochem Int 27:95-103
Long, Y; Frederickson, C J (1994) A zinc-containing fiber system of thalamic origin. Neuroreport 5:2026-8
Frederickson, C J; Rampy, B A; Reamy-Rampy, S et al. (1992) Distribution of histochemically reactive zinc in the forebrain of the rat. J Chem Neuroanat 5:521-30
Howell, G A; Perez-Clausell, J; Frederickson, C J (1991) Zinc containing projections to the bed nucleus of the stria terminalis. Brain Res 562:181-9
Frederickson, C J; Danscher, G (1990) Zinc-containing neurons in hippocampus and related CNS structures. Prog Brain Res 83:71-84
Frederickson, R E; Frederickson, C J; Danscher, G (1990) In situ binding of bouton zinc reversibly disrupts performance on a spatial memory task. Behav Brain Res 38:25-33
Tonder, N; Johansen, F F; Frederickson, C J et al. (1990) Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. Neurosci Lett 109:247-52
Morton, J D; Howell, G A; Frederickson, C J (1990) Effects of subcutaneous injections of zinc chloride on seizures induced by noise and by kainic acid. Epilepsia 31:139-44
Slomianka, L; Danscher, G; Frederickson, C J (1990) Labeling of the neurons of origin of zinc-containing pathways by intraperitoneal injections of sodium selenite. Neuroscience 38:843-54

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