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Examining the contribution of dentate gyrus granule cells and ambiguity toward the stress response and behaviour of the rodent

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posted on 2017-05-16, 12:59 authored by lucas gloverlucas glover
The hippocampus and adult-born neurons have been implicated in regulating the stress response and disambiguating conflicting goal-related information. How these functions interact to promote adaptive behaviour has not been investigated. In this thesis, hippocampal lesions or pharmaco-genetic ablation of adult neurogenesis in mice ('TK mice') was used to dissect this relationship. Hippocampal lesions or selectively ablating adult neurogenesis decreased defensive behaviours toward a partially reinforced fear conditioned cue ('ambiguous fear conditioning'). Conversely, these animals did not show these impairments when a cue reliably predicted a footshock ('reliable fear conditioning'). In TK mice, this same pattern of results was also seen in Fos expression levels in the dentate gyrus and CA3. In additional experiments, baseline novelty-suppressed feeding behaviour (latency to eat a familiar food) did not differ between genotypes. After reliable fear conditioning, TK mice took longer to eat the food, suggesting increased anxiodepressive-like behaviour. After ambiguous fear conditioning, however, TK showed quicker latencies to eat, suggesting decreased anxiodepressive-like behaviour, as compared to wildtype mice. Clamping corticosterone levels was used to determine its role in adaptive responding to prior stress. Preventing experience-induced increases in corticosterone did decrease the latency for wildtype mice to eat after ambiguous fear conditioning, whereas TK mice were unaffected. Finally, another set of experiments were designed to see if ambiguity would affect appetitive behaviour in a non-spatial T-maze task with conflicting goal responses. It was found that mice with hippocampal lesions, but not TK mice, tended to choose an arm associated with a large reward less often if the other arm contained a small reward, as compared to their respective control groups. Similarly, hippocampal-lesioned mice, but not TK mice, chose an arm that was always associated with the presence of a reward less often if the other arm ambiguously predicted a reward. All of the above results suggest that the hippocampus, especially adult-born neurons, is necessary to disambiguate salient conflicting memories that underlie goal responses and that this disambiguation biases goal-related behaviour in an adaptive manner.