Neural mechanisms of stimulus generalization in auditory fear conditioning

Dissertation presented to obtain the Ph.D degree in Neuroscience Instituto de Tecnologia Química e Biológica, Universidade Nova de LisboaFear is a physiological trait with a strong weight on survival and adaptation. Great progress has been made to understand the mechanisms of fear learning, mainly using auditory fear conditioning (AFC). In this behavioral paradigm, an initial neutral tone (conditioned stimulus, CS) acquires aversive predictive properties after successive pairings with a footshock (unconditioned stimulus, US) and comes to elicit responses characteristically elicited by threatening stimuli. In this behavioral paradigm, the amygdala has been identified has a key neural substrate for associative fear learning, and the site where unconditioned stimuli (US) and conditioned (CS) auditory stimuli come to be associated. Auditory information may reach the amygdala either directly from the auditory thalamus or indirectly via thalamo-cortico-amygdala projections. The “high route/low route” hypothesis has thus been proposed, which claims that the cortical pathway (“high route”) is crucial for discrimination between fearful and neutral sounds, while the direct thalamic pathway (“low route”) provides a rapid but less accurate relay of auditory information to the amygdala. This hypothesis relies on the assumption that more complex processing requires cortical activity and that thalamic relay is faster then cortical transmission to the amygdala. The present work essentially aims at putting to test this largely accepted hypothesis.Auditory fear conditioning was used as the behavioral paradigm to unravel the possible functional explanation for the coexistence of two parallel auditory pathways converging into the amygdala, and the high route/low route hypothesis was the working model for the identification of neuronal substrates of auditory discrimination.(...)This work was supported by Fundação para a Ciência e a Tecnologia (Grant SFRH/BD/27500/2006)