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.
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