A central issue in behavioral neuroscience is how alterations in neural pathways mediate the durable behavior changes involved in learning. Taste aversion conditioning provides an excellent model for studying the neural changes which underlie learning because conditioning can occur in a single trial, despite lengthy delays between conditioned and unconditioned stimuli. It is also a form of learning which occurs in humans as a result of illness or treatment for illness, with deleterious effects on appetite. The proposed studies are based on identification of cell groups and neural circuitry activated during taste aversion learning. Neural activation will be assessed by immunostaining for the protein product of the immediate early gene, c-fos. Proposed studies will address both taste aversion acquisition and expression. In addressing taste aversion expression, studies will determine whether cells in the nucleus of the solitary tract which are activated during expression project to the pontine parabrachial nucleus and/or the paraventricular nucleus of the hypothalamus as part of a circuit involved in the generation of visceral conditioned reactions to the aversive taste. Studies will also determine whether activation of these cells, as well as behavioral expression of the taste aversion, require input from discrete regions of amygdala and parabrachial nucleus. Studies addressing taste aversion acquisition will use knockout mouse models with specific deletions of protein kinase A (PKA) genes. Preliminary studies using mice with a specific deletion of a PKA gene, R11B have demonstrated that these mice are unable to acquire a conditioned taste aversion and show a specific defect in the induction of cFos protein in basolateral amygdala in response to LiCl. Proposed studies will determine whether the activation of c-fos expression by cells within the basolateral amygdala, in response to the unconditioned stimulus, LiCl, is required for acquisition and whether the observed defect in taste aversion learning in null mutant mice is limited to the long-term, but not the short-term, version of their taste aversion memory. Additional mouse strains with other selective deficits in PKA genes will be assessed for their learning and the induction of cFos protein in basolateral amygdala. By defining the neural pathways and cell types involved in conditioned taste aversion learning this project will provide the groundwork for eventually characterizing the plastic changes within and between cells which underlie this robust form of gustatory learning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS037040-04A1
Application #
6399828
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Edwards, Emmeline
Project Start
1998-01-12
Project End
2005-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
2001
Total Cost
$186,672
Indirect Cost
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Chung, Ain; Barot, Sabiha K; Kim, Jeansok J et al. (2011) Biologically predisposed learning and selective associations in amygdalar neurons. Learn Mem 18:371-4
Kim, Min Jung; Mizumori, Sheri J Y; Bernstein, Ilene L (2010) Neuronal representation of conditioned taste in the basolateral amygdala of rats. Neurobiol Learn Mem 93:406-14
Clark, Emily Wilkins; Bernstein, Ilene L (2009) Establishing aversive, but not safe, taste memories requires lateralized pontine-cortical connections. Behav Brain Res 197:356-63
Barot, Sabiha K; Chung, Ain; Kim, Jeansok J et al. (2009) Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian fear conditioning. PLoS One 4:e6156
Clark, Emily Wilkins; Bernstein, Ilene L (2009) Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning. Behav Neurosci 123:764-71
Barot, Sabiha K; Kyono, Yasuhiro; Clark, Emily W et al. (2008) Visualizing stimulus convergence in amygdala neurons during associative learning. Proc Natl Acad Sci U S A 105:20959-63
Wilkins, Emily E; Bernstein, Ilene L (2006) Conditioning method determines patterns of c-fos expression following novel taste-illness pairing. Behav Brain Res 169:93-7
Koh, Ming Teng; Bernstein, Ilene L (2005) Mapping conditioned taste aversion associations using c-Fos reveals a dynamic role for insular cortex. Behav Neurosci 119:388-98
Barot, Sabiha K; Bernstein, Ilene L (2005) Polycose taste pre-exposure fails to influence behavioral and neural indices of taste novelty. Behav Neurosci 119:1640-7
Spray, Kristina J; Bernstein, Ilene L (2004) Afferent and efferent connections of the parvicellular subdivision of iNTS: defining a circuit involved in taste aversion learning. Behav Brain Res 154:85-97

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