This proposal will explore the detailed anatomy of the basal forebrain, with particular focus on the ventral striatopallidal system and the """"""""extended amygdala"""""""" and their potential output channels through the diencephalon and brainstem including their relation to corticopetal neurons in mediobasal telencephalon. Specific attempts will be made to explore cellular interactions in the sublenticular area and the lateral hypothalamus. In order to achieve this goal, two-neuron pathways originating in various compartments of the ventral striatopallidal system and extended amygdala will be examined both on the light- and the electron microscopic levels using a combination of axonal transport methods and intracellular labelling techniques. In particular, lateral hypothalamic or sublenticular neurons that have been identified by retrograde labelling following injections of the tracer in their area of termination, will be injected with Lucifer Yellow or a comparable substance to visualize their dendritic branches and their relation to incoming afferent pathways labeled with anterograde tracer techniques. When appropriate, immunohistochemical techniques or in-situ hybridization will be used to identify the transmitters of the interacting neuronal elements. The exploration of the basal forebrain will also be carried to the human brain with the particular goal of identifying by means of histochemical methods or in-situ hybridization, presynaptic transmitters to morphologically characterized neurons, particularly in the ventral striatopallidum, extended amygdala, and the basal nucleus of Meynert. The basal forebrain systems to be explored in this study are involved to a significant degree in a number of crippling brain disorders including Alzheimer's disease. Parkinson's disease, and schizophrenia, and the anatomical studies proposed in this application will provide the details necessary to provide a conceptual framework for physiologic, behavioral and clinical studies of forebrain functions relevant to these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017743-12
Application #
3397830
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1981-01-01
Project End
1998-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Alheid, George F (2003) Extended amygdala and basal forebrain. Ann N Y Acad Sci 985:185-205
Shammah-Lagnado, S J; Alheid, G F; Heimer, L (2001) Striatal and central extended amygdala parts of the interstitial nucleus of the posterior limb of the anterior commissure: evidence from tract-tracing techniques in the rat. J Comp Neurol 439:104-26
Heimer, L (2000) Basal forebrain in the context of schizophrenia. Brain Res Brain Res Rev 31:205-35
Shammah-Lagnado, S J; Beltramino, C A; McDonald, A J et al. (2000) Supracapsular bed nucleus of the stria terminalis contains central and medial extended amygdala elements: evidence from anterograde and retrograde tracing experiments in the rat. J Comp Neurol 422:533-55
Shammah-Lagnado, S J; Alheid, G F; Heimer, L (1999) Afferent connections of the interstitial nucleus of the posterior limb of the anterior commissure and adjacent amygdalostriatal transition area in the rat. Neuroscience 94:1097-123
Alheid, G F; Shammah-Lagnado, S J; Beltramino, C A (1999) The interstitial nucleus of the posterior limb of the anterior commissure: a novel layer of the central division of extended amygdala. Ann N Y Acad Sci 877:645-54
de Olmos, J S; Heimer, L (1999) The concepts of the ventral striatopallidal system and extended amygdala. Ann N Y Acad Sci 877:1-32
Alheid, G F; Beltramino, C A; De Olmos, J S et al. (1998) The neuronal organization of the supracapsular part of the stria terminalis in the rat: the dorsal component of the extended amygdala. Neuroscience 84:967-96
Gaykema, R P; Zaborszky, L (1997) Parvalbumin-containing neurons in the basal forebrain receive direct input from the substantia nigra-ventral tegmental area. Brain Res 747:173-9
Kaufmann, W A; Barnas, U; Maier, J et al. (1997) Neurochemical compartments in the human forebrain: evidence for a high density of secretoneurin-like immunoreactivity in the extended amygdala. Synapse 26:114-30

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