Abstract

The long range objective of this laboratory is to understand the cellular and circuit basis of cognitive operations of the prefrontal cortex, the brain area closely associated with the executive functions of the human brain. In the past cycle of this grant, we have defined separate spatial and nonspatial visual processing domains associated with the dorsolateral and inferior prefrontal convexities, respectively. The goal of the present application is to functionally and anatomically dissect the intrinsic circuit mechanisms by which the prefrontal cortex performs its basic cognitive operations and to test the hypothesis that the prefrontal cortex is composed of content- constrained modules not only at the level of cytoarchitectonic areas (macroarchitecture) but also at the level of columns and microcolumns (microarchitecture).
In Specific Aim number 1, powerful new multielectrode technology will be applied in vivo to the study of the dorsolateral prefrontal cortex to examine the dynamic interactions of ensembles of neurons with cue, delay and action-related response properties within and across cortical columns during spatial working memory tasks. This method will also allow analysis of the contributions of fast-spiking (putative interneurons) and regular spiking (putative pyramidal) neurons to these dynamic interactions and spatial memory field formation in the dorsolateral cortex.
In Specific Aim number 2, the same powerful method will be applied to the object processing system of the inferior prefrontal cortex (IFC) to assess ensemble encoding in relation to the object/face response properties of IFC neurons.
Specific Aim number 3 will complement the in vivo approach by employing whole cell patch clamp recording combined with infrared microscopy to visualize and directly study local circuits among functionally connected neurons in cortical slices. Collectively, these aims will explore a new level of functional anatomy in prefrontal cortex with the goal of providing mechanistic explanations of cognitive phenomena and insight into pathological processes of mental illness.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038546-25
Application #
6718358
Study Section
Special Emphasis Panel (ZRG1-IFCN-8 (01))
Program Officer
Anderson, Kathleen C
Project Start
1980-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2006-03-31
Support Year
25
Fiscal Year
2004
Total Cost
$791,296
Indirect Cost

  Institution

Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

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

Showing the most recent 10 out of 81 publications