Anterior cingulate cortex has been implicated in affective responses to noxious stimuli contains opioid synthesizing neurons and has high densities of mu and delta opioid receptors. It is not known which neuronal processes bind opioid receptor ligands. The present experiments will employ experimental localization techniques developed by the P.I. for localizing axonal and dendritic muscarinic acetylcholine receptor subtypes. For whole section analysis one of three types of lesions will be made in rat brain followed by assay of mu and delta-selective ligand binding in cryomicrotome sections, coverslip autoradiography and single grain counting in anterior cingulate cortex: 1) full depth or laminar ibotenic acid, 2) selective destruction of cortical projection neurons following injections of the immunotoxin OX7-ss- saporin into the caudate or periaqueductal gray nuclei or into posterior cingulate cortex, 3) deafferentation undercut lesions. A second localization approach will involve prelabeling of caudate, periaqueductal gray or cortical projection neurons with a stable, retrogradely transported fluorescent dye. Cortical neurons will then be enzymatically and mechanically dissociated and assayed for mu-selective binding of beta-funaltrexamine to prelabeled pyramidal neurons and unlabeled pyramidal and multipolar neurons. Another series of experiments will evaluate mu and delta sites in cortical sublaminae and thalamic subnuclei in cryomicrotome sections of rabbit and human brains. As a number of thalamic and cortical connections are likely involved in sensorimotor aspects of responses to noxious stimuli, multiple label connection studies are also proposed to analyze thalamocortical and corticocortical connections of rabbit cingulate cortex. Studies in thalamus will emphasize the lateral magnocellular nucleus because its connections have not been described and it is not known to exist in any other mammal. Studies at the cortical level will emphasize topographic relations among cingulate areas and among cingulate and visual areas. The main goals of these studies are to elucidate a direct means by which opiate and opioid compounds influence cortical neurons which project to autonomic and somatic motor centers, characterize the distribution of opioid receptors on the dendrites and somata of pyramidal projection neurons and multipolar interneurons and describe the connections of a virtually unknown nucleus in rabbit thalamus. Dissociated adult cortical neurons can be used in future studies to evaluate mechanisms of up and down regulation of opioid receptors as well as gating of ionic channels by opioid compounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS018745-09
Application #
3398783
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1982-07-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1992-08-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Vogt, B A; Crino, P B; Vogt, L J (1992) Reorganization of cingulate cortex in Alzheimer's disease: neuron loss, neuritic plaques, and muscarinic receptor binding. Cereb Cortex 2:526-35
Sikes, R W; Vogt, B A (1992) Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 68:1720-32
Vogt, B A; Crino, P B; Jensen, E L (1992) Multiple heteroreceptors on limbic thalamic axons: M2 acetylcholine, serotonin1B, beta 2-adrenoceptors, mu-opioid, and neurotensin. Synapse 10:44-53
Vogt, L J; Vogt, B A; Sikes, R W (1992) Limbic thalamus in rabbit: architecture, projections to cingulate cortex and distribution of muscarinic acetylcholine, GABAA, and opioid receptors. J Comp Neurol 319:205-17
Vogt, B A; Crino, P B; Volicer, L (1991) Laminar alterations in gamma-aminobutyric acidA, muscarinic, and beta adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer's disease. J Neurochem 57:282-90
Vogt, B A; Sikes, R W (1990) Lateral magnocellular thalamic nucleus in rabbits: architecture and projections to cingulate cortex. J Comp Neurol 299:64-74
Vogt, B A; Plager, M D; Crino, P B et al. (1990) Laminar distributions of muscarinic acetylcholine, serotonin, GABA and opioid receptors in human posterior cingulate cortex. Neuroscience 36:165-74
Vogt, B A; Van Hoesen, G W; Vogt, L J (1990) Laminar distribution of neuron degeneration in posterior cingulate cortex in Alzheimer's disease. Acta Neuropathol 80:581-9
Crino, P B; Vogt, B A; Volicer, L et al. (1990) Cellular localization of serotonin 1A, 1B and uptake sites in cingulate cortex of the rat. J Pharmacol Exp Ther 252:651-6
Townes-Anderson, E; Vogt, B A (1989) Distribution of muscarinic acetylcholine receptors on processes of isolated retinal cells. J Comp Neurol 290:369-83

Showing the most recent 10 out of 21 publications