Developmental neurobiologists have employed numerous models to examine the influence of sensory inputs on the maturation of higher-order neurons in the CNS. This intense effort is not surprising, since a better comprehension of these interactions is essential to our ultimate understanding of the normal development of the brain, as well as the brain's response to injury. It is postulated that the morphology of the developing gustatory neurons in the rostral nucleus of the solitary tract (rNST) of the rat is modified in response to changes in the nature of the primary afferent input. It is further proposed that the morphology of specific subsets of rNST neurons that are most sensitive to specific tastants can be altered by decreasing or increasing the animal's exposure to that tastant during early postnatal life. To address these and related hypotheses, two principal Specific Aims are proposed.
The first aim will be to characterize the normal development of structure-function relationships of gustatory neurons in the rNST of the rat. This information will provide the necessary foundation for the second aim, which is to determine the effect of altering one component of the gustatory environment on the development of structure-function relationships in this nucleus. Proposed research will begin by using intracellular recording and labeling techniques to determine the morphology of individual physiologically- characterized rNST neurons in rats on postnatal days 10, 20-22 and 28-30. Each neuron will be tested for its response to a standard series of taste stimuli and then labeled by intracellular iontophoretic injection of Neurobiotin. The labeled neurons will be subjected to three-dimensional qualitative and quantitative analysis, the morphological characteristics will be correlated with physiological response properties and the resultant structure-function relationships will be compared to those previously established in adult animals. Studies are then planned to alter the normal gustatory input to the NST in two separate series of experiments. In the first series, a Na-deprivation model will be employed to reduce the NaCl- related input to neurons in the NST. In a separate series of experiments, the developmental impact of selectively increasing the animal's exposure to one tastant by lavaging the oral cavity with 0.01M quinine hydrochloride 3 times each day from birth will be examined. In each case comparisons will be made between the development of rNST structure-function relationships and the relationships identified in normal animals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001074-08
Application #
2900035
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1992-04-01
Project End
2000-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Heck, W L; Basaraba, A M; Slusarczyk, A et al. (2003) Early GABA(A) receptor clustering during the development of the rostral nucleus of the solitary tract. J Anat 202:387-96
Heck, Wendy L; Slusarczyk, Arkadiusz; Basaraba, Ana Maria et al. (2002) Subcellular localization of GABA receptors in the central nervous system using post-embedding immunohistochemistry. Brain Res Brain Res Protoc 9:173-80
Heck, W L; Renehan, W E; Schweitzer, L (2001) Redistribution and increased specificity of GABA(B) receptors during development of the rostral nucleus of the solitary tract. Int J Dev Neurosci 19:503-15
Brown, M; Renehan, W E; Schweitzer, L (2000) Changes in GABA-immunoreactivity during development of the rostral subdivision of the nucleus of the solitary tract. Neuroscience 100:849-59
Leonard, N L; Renehan, W E; Schweitzer, L (1999) Structure and function of gustatory neurons in the nucleus of the solitary tract. IV. The morphology and synaptology of GABA-immunoreactive terminals. Neuroscience 92:151-62
Wetherton, B M; Leonard, N L; Renehan, W E et al. (1998) Structure and function of gustatory neurons in the nucleus of the solitary tract. III. Classification of terminals using cluster analysis. Biotech Histochem 73:164-73
Renehan, W E; Massey, J; Jin, Z et al. (1997) Developmental changes in the dendritic architecture of salt-sensitive neurons in the nucleus of the solitary tract. Brain Res Dev Brain Res 102:231-46
Schweitzer, L; Renehan, W E (1997) The use of cluster analysis for cell typing. Brain Res Brain Res Protoc 1:100-8
Renehan, W E; Jin, Z; Zhang, X et al. (1996) Structure and function of gustatory neurons in the nucleus of the solitary tract: II. Relationships between neuronal morphology and physiology. J Comp Neurol 367:205-21
Renehan, W E; Zhang, X; Beierwaltes, W H et al. (1995) Neurons in the dorsal motor nucleus of the vagus may integrate vagal and spinal information from the GI tract. Am J Physiol 268:G780-90

Showing the most recent 10 out of 12 publications