The frontal lobes reach their highest development in man, in whom they are thought to provide the neural basis for the analysis of past and future actions, the programming of sequential behaviors toward long-range goals, and the regulation of socially and culturally appropriate behavior. The ultimate goal of this research program is to understand the frontal lobes and their contribution to higher-order cognitive functions by detailed experimental study of its anatomy, physiology, neurochemistry and behavioral expression in nonhuman primates. The same studies should provide a neurobiological basis for understanding a variety of behavioral disorders that reflect disease in the frontal cortex and anatomically related structures such as the basal ganglia and basal forebrain. This program has evolved during the last decade to its present focus on: (1) anatomical organization with particular emphasis on microstructural analysis of the topographic, laminar and columnar organization, and degree of collateralization of prefrontal cortical connections using advanced neuroanatomical tracing techniques including autoradiography, fluorescent tracers, and horseradish peroxidase histochemistry; (2) neurochemical organization of prefrontal pathways including neurotransmitters, enzymes and receptors using immunohistochemistry, electron microscopy, and receptor autoradiography; (3) functional analysis of prefrontal cortex using lesion behavioral analysis, 2-deoxyglucose autoradiography for mapping metabolic activity and electrophysiology alone or in combination with anatomical methods; and (4) comparative and life-span developmental studies to establish a link between studies of prefrontal cortex in nonhuman primates and in man by analysis of a variety of behaviors common to both species. All experiments are conducted on rhesus monkeys whose association cortex including the prefrontal cortex is well developed and who are unexcelled laboratory animal models for the study of cortical function. By design, our strategy is multidisciplinary, but each project intersects with every other, both conceptually and technically. The proposed studies should enrich our understanding of the neural circuits and cellular basis of cognitive functions and their breakdown in mental disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038546-09
Application #
3376719
Study Section
(BPNB)
Project Start
1980-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
9
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Negyessy, Laszlo; Bergson, Clare; Garab, Sandor et al. (2008) Ultrastructural localization of calcyon in the primate cortico-basal ganglia-thalamocortical loop. Neurosci Lett 440:59-62
Gao, Wen-Jun; Goldman-Rakic, Patricia S (2006) NMDA receptor-mediated epileptiform persistent activity requires calcium release from intracellular stores in prefrontal neurons. Exp Neurol 197:495-504
Tanibuchi, Ikuo; Goldman-Rakic, Patricia S (2005) Comparison of oculomotor neuronal activity in paralaminar and mediodorsal thalamus in the rhesus monkey. J Neurophysiol 93:614-9
Negyessy, L; Goldman-Rakic, P S (2005) Morphometric characterization of synapses in the primate prefrontal cortex formed by afferents from the mediodorsal thalamic nucleus. Exp Brain Res 164:148-54
Negyessy, Laszlo; Goldman-Rakic, Patricia S (2005) Subcellular localization of the dopamine D2 receptor and coexistence with the calcium-binding protein neuronal calcium sensor-1 in the primate prefrontal cortex. J Comp Neurol 488:464-75
Leung, H-C; Gore, J C; Goldman-Rakic, P S (2005) Differential anterior prefrontal activation during the recognition stage of a spatial working memory task. Cereb Cortex 15:1742-9
Koos, Tibor; Tepper, James M; Wilson, Charles J (2004) Comparison of IPSCs evoked by spiny and fast-spiking neurons in the neostriatum. J Neurosci 24:7916-22
Wang, Yun; Goldman-Rakic, Patricia S (2004) D2 receptor regulation of synaptic burst firing in prefrontal cortical pyramidal neurons. Proc Natl Acad Sci U S A 101:5093-8
Leung, Hoi-Chung; Seelig, David; Gore, John C (2004) The effect of memory load on cortical activity in the spatial working memory circuit. Cogn Affect Behav Neurosci 4:553-63
Tanibuchi, Ikuo; Goldman-Rakic, Patricia S (2003) Dissociation of spatial-, object-, and sound-coding neurons in the mediodorsal nucleus of the primate thalamus. J Neurophysiol 89:1067-77

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