The long term objective is the imaging of the neural substrates involved in associative learning and memory of auditory signals. The basic goal is to examine how the same physical stimulus (a frequency modulated tone) affects metabolic activity in the auditory system when the tone serves different behavioral roles. The experiments will also map in detail the rat brain to identify the associative effects of the tone outside the auditory system. We propose to answer three questions about auditory Pavlovian conditioning at the systems level: 1) What changes in brain activity are related to the effects of the same tone conditioned as an excitor or inhibitor? 2) What neural structures are involved in the inhibition of the conditioned response to a tone excitor by a light inhibitor? 3) What neural structures are involved in the blocking of tone conditioning by a light excitor? These questions relate to behavioral inhibitory features of associative learning involving different interactions of the same stimuli (tone and light) in the presence or absence of the reinforcer (footshock). The kind of interaction determines the associative behavioral effects of the tone. Therefore, different neural effects can be systematically investigated using the same stimuli in two behavioral paradigms, conditioned inhibition and blocking. These paradigms were chosen to investigate neural substrates related to three key notions in modern thinking about associative learning: inhibition, information, and contiguity. The neural effects mediating these phenomena are fundamental to help understand processes involved in the development of Pavlovian associations. Appropriate control conditions will also be evaluated for each paradigm. In every case, behavioral learning effects will be tested using conditioned suppression of drinking. Imaging of neural effects will be done with two metabolic mapping techniques combined and adapted to map learning effects on the same brain. They incorporate quantitative autoradiographic mapping of fluorinated 2-deoxyglucose (2-DG) uptake and quantitative histochemical mapping of cytochrome oxidase (CO) activity. The 2-DG mapping serves to evaluate stimulus-dependent changes in metabolic activity evoked by the tone during behavioral testing (short-term effect). The CO mapping serves to evaluate long-lasting modifications in metabolic capacity produced by the different training paradigms (long-term effect). Since the mapping techniques provide information of how entire neural systems change within one brain, an approach known as structural modeling will be used to quantify within-brain changes in the operation of each system involved. This approach is a within-subject mathematical modeling method recently adapted for the analysis of brain imaging data at the systems level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH043353-06
Application #
3382805
Study Section
Psychobiology and Behavior Review Committee (PYB)
Project Start
1988-08-01
Project End
1996-08-31
Budget Start
1992-09-30
Budget End
1993-08-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Pharmacy
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Mcintosh, A R; Gonzalez-Lima, F (1998) Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J Neurophysiol 80:3148-62
Gonzalez-Lima, F; Valla, J; Matos-Collazo, S (1997) Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients. Brain Res 752:117-26
de la Torre, J C; Cada, A; Nelson, N et al. (1997) Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats. Neurosci Lett 223:165-8
Poremba, A; Jones, D; Gonzalez-Lima, F (1997) Metabolic effects of blocking tone conditioning on the rat auditory system. Neurobiol Learn Mem 68:154-71
Jones, D; Gonzalez-Lima, F; Crews, D et al. (1997) Effects of intrauterine position on the metabolic capacity of the hypothalamus of female gerbils. Physiol Behav 61:513-9
Cada, A; Gonzalez-Lima, F; Rose, G M et al. (1995) Regional brain effects of sodium azide treatment on cytochrome oxidase activity: a quantitative histochemical study. Metab Brain Dis 10:303-20
McIntosh, A R; Gonzalez-Lima, F (1995) Functional network interactions between parallel auditory pathways during Pavlovian conditioned inhibition. Brain Res 683:228-41
McIntosh, A R; Gonzalez-Lima, F (1994) Network interactions among limbic cortices, basal forebrain, and cerebellum differentiate a tone conditioned as a Pavlovian excitor or inhibitor: fluorodeoxyglucose mapping and covariance structural modeling. J Neurophysiol 72:1717-33
Gonzalez-Lima, F; Cada, A (1994) Cytochrome oxidase activity in the auditory system of the mouse: a qualitative and quantitative histochemical study. Neuroscience 63:559-78
Gonzalez-Lima, F; Ferchmin, P A; Eterovic, V A et al. (1994) Metabolic activation of the brain of young rats after exposure to environmental complexity. Dev Psychobiol 27:343-51

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