This continuation (years 17-20) describes experiments designed to investigate the structural organization of the mesocortices of the limbic lobe in the monkey and human brain. In its initial years, reinnervation of the amygdala was investigated and the term """"""""plasticity"""""""" in the title has continued with the grant, although it is not longer descriptive of the research proposed. A central goal has been to investigate cortical association axons that link the association areas with the mesocortices. The reciprocal of this relationship has been investigated as well. In 1989 Alzheimer's disease research was added as a new direction since it targets the exact neurons that mediate this relationship. In the grant's last competitive review dual efforts relating to Alzheimer's disease research and nonhuman primate experimental neuroanatomical research were proposed, and the grant received a Javits Neuroscience Investigator Award. In this proposal, three new aims are outlined. Two deal with combined human and monkey investigations and aim to analyze Brodmann's areas 35 and 34. The former interconnects the entorhinal mesocortices with the temporal isocortices. Area 35 is understood poorly in the human brain and the first to develop neurofibrillary tangles in Alzheimer's disease. Monkey behavioral studies link it closely to associative memory. Area 34 forms the anterior and medial entorhinal cortex and contains laminar alterations in some brains of schizophrenics. It is damaged directly in all types of partial and traumatic herniation of medial temporal lobe through the incisura of the tentorium cerebelli. Cellular phenotypes and boundaries will be established for these areas, focusing both on projection and intrinsic neurons. An additional aim utilizes only the monkey and will assess """"""""three neuron"""""""" neural systems related to the mesocortices. Specifically, the terminal fields of entorhinal neurons will be injected with a retrograde tracer and the labeled neurons will be filled intracellularly with Lucifer yellow to reveal their morphology. In the same preparation afferent axons projecting to characterized entorhinal neurons will be anterogradely labeled to establish their putative input patterns to the filled neuron. Confocal laser scanning microscopy will be used to analyze these preparations. For all aims, the data will provide baseline neuroscience information for cortical areas known to be involved in developmental, neurological and psychiatric disease. It is cost effective research that draws on a collection of non-human primate and human material gathered over the past 27 years at Harvard Medical School (1969-1978) and The University of Iowa (1979-present).
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