Research over the past several decades has revealed that the amygdala is involved in aversive, or fear, conditioning. However, the precise nature of this involvement remains a matter of debate. One hypothesis suggests that disrupting amygdala function eliminates the storage of memories formed during aversive conditioning, eliminating the production of internal responses that alter the expression of observable behaviors. Alternatively, lesions or inactivation of the amygdala may impair the modulation of memories in other brain regions and disrupt the ability to perform certain observable behaviors. The experiments reported in the present thesis examined these arguments by making multiple behavioral measures during exposure to unconditioned (US) or conditioned (CS) aversive cues. Amygdala activity was inferred from changes in c-Fos protein expression or activity was temporarily suppressed with muscimol injections. The relationship between the behavioral measures and the role of the amygdala in producing them was examined. Amygdala neurons expressing the c-Fos protein tracked exposure to the US and CS but did not coincide with expression of freezing. Temporary inactivation of the amygdala with muscimol injections before presentation of the US or exposure to the CS attenuated the expression of freezing and active place avoidance; two incompatible behaviors. Finally, temporary inactivation of amygdala activity blocked freezing, place avoidance, and memory modulation produced by the same posttraining exposure to an aversive CS. Since amygdala activation alone was not sufficient to produce freezing and inactivation of the amygdala eliminated freezing, place avoidance, and memory modulation, the results cannot be interpreted as reflecting a direct role for the amygdala in production of observable behaviors. The results also preclude the idea that memory modulation is the only function of the amygdala. Rather, the results of all three studies suggest that the amygdala stores an aversive representation of the US which promotes the expression of various behaviors, possibly through the production of internal responses reflecting an aversive affective state.

In classical conditioning the amygdala is a critical area for the convergence of the unconditioned (US) and conditioned stimulus (CS). During this process the CS acquires some of the properties of the US. By assessing the US properties of foot-shock, namely reflex, pain and fear, the neural systems of pain and fear were evaluated in the rat basolateral and central amygdala. The central fear state produced by footshock was compared to the central fear state expressed during the fear-potentiated startle paradigm. By analysing the similarities and differences in the fear states, the effects of GABAergic, glutamatergic, and dopaminergic systems and protein synthesis inhibition on these fear states were investigated. The basolateral amygdala was sensitive to GABAergic modulation during US and CS presentations. This was interpreted as a central fear effect. The central amygdala was sensitive to glutamate but not to GABAergic modulation. NMDA receptor antagonism prevented fear arousal to US but not CS presentation. This effect was interpreted as a deficit in pain processing. Non-NMDA receptor antagonism could significantly attenuate both US and CS fear expression. This was interpreted as an overall non-NMDA receptor inhibitory effect that affected pain and conditioned fear expression. Results of these experiments have implications for our understanding of the circuitry involved in processing the US. The basolateral amygdala appears to support emotional neural plasticity while the central amygdala appears to support pain neural plasticity. Finally and and most importantly each area processes different properties of the US.

Thesis (Ph.D.). / Written for the Dept. of Psychology. Title from title page of PDF (viewed 2008/08/04). Includes bibliographical references.

Temporal lobe epileptics often experience interictal (i.e., between-seizure) emotional disturbances such as fear and anxiety. Despite the problem that these disturbances present, little progress has been made in characterizing their nature and etiology because they are not amenable to experimental analysis in clinical populations. Accordingly, the general purpose of the experiments in this thesis was to demonstrate the potential of long-term amygdala kindling in rats as a model of the interictal hyperemotionality of temporal lobe epileptics. Seven experiments comprise this thesis. Experiments 1 and 2 established that longterm amygdala kindling (i.e., 100 stimulations) results in large and reliable increases in emotionality. In Experiment 1, the long-term amygdala-kindled rats displayed more resistance to capture from an open field and more open-arm activity on an elevated plus maze than did the sham-stimulated rats; in Experiment 2, the magnitude of this hyperemotionality was shown to be dependent on the number of amygdala stimulations that the rats received. Experiment 3 showed that kindling-induced hyperemotionality is enduring; the hyperemotionality present 1 day after the final stimulation did not decline significantly over the ensuing month although some amelioration of symptoms was observed. Experiment 4 established that kindling-induced hyperemotionality is not unique to amygdala stimulation. Although increases in emotionality were greatest in amygdalakindled rats, hippocampal-kindled, but not caudate-kindled, rats also displayed significant increases. Experiments 5 and 6 showed that kindling-induced hyperemotionality is fundamentally defensive in nature. In Experiment 5, amygdala-kindled rats displayed high levels of emotionality in an unfamiliar, but not in a familiar, situation; in Experiment 6, amygdala-kindled rats displayed more defensive, but less aggressive behaviour, in their interactions with other rats. Finally, Experiment 7 showed that 8-OH-DPAT binding to serotonin 5HT1A receptors is increased in the dentate gyrus of amygdala-kindled rats, but not in the amygdala, periaqueductal grey, perirhinal cortex, or CA1 or CA3 hippocampal subfields. Together, the results of these experiments establish the potential of long-term amygdala kindling as a useful animal model of interictal emotionality in temporal lobe epileptics. / Arts, Faculty of / Psychology, Department of / Graduate

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Thesis (Ph. D.)--Michigan State University. Neuroscience Program, 2008. / Title from PDF t.p. (viewed on Mar. 26, 2009). Includes bibliographical references (p. 109-119). Also issued in print.

Thesis (M.A.)--Baylor University, 2007. / Includes bibliographical references (p. 34-38).

Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Integrative Neuroscience." Includes bibliographical references (p. 111-123).