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Title: Serotonin transporter function and emotional behaviour
Author: Lima, João
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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The serotonin transporter (5-HTT) is a key regulator of synaptic serotonin (5-HT), a monoamine that is significantly involved in the regulation of fear and anxiety processes. Importantly, low or null 5-HTT expression levels have also been associated with anxious and depressive phenotypes in several species. This remains controversial, however, with different research groups reporting conflicting results with most of the methodologies used so far to investigate whether such an association exists. An emerging 'neuroplasticity theory of 5-HT function' argues that low 5-HTT-expressing individuals, who are thought to have increased 5-HT availability, are not more vulnerable to anxious and depressive phenotypes per se but more sensitive to aversive and non-aversive life events. Subsequently, this increased sensitivity could lead to facilitated emotional learning in a 'for-better-or-for-worse' manner depending on their experiences in a given environment. This thesis aimed to investigate this further by testing knockout mice for the 5-HTT (5-HTTKO mice) in approach-avoidance conflict tests, social assays and discrimination learning tasks with negative and positive emotional stimuli. Additionally, in a subset of mice, altered basolateral amygdala (BLA) function during an aversive learning task was also investigated via recordings of neuronal and haemodynamic responses to emotional cues. The experiments reported here have shown that 5-HTTKO mice exhibit altered sensitivity towards emotionally-relevant negative and positive events and towards social influences. Moreover, 5-HTTKO mice exhibited superior aversive learning via augmented BLA function. However, the nature of the stimuli used in the experiments was crucial for the observation of such facilitated learning, given that learning about reward-predicting cues was not facilitated in 5-HTTKO mice. Overall, the results obtained in this thesis provide evidence for the neuroplasticity theory of 5-HT function at the behavioural and neurophysiological level. However, further studies are warranted to clarify the boundaries of this theory.
Supervisor: McHugh, Stephen B. ; Bannerman, David M. Sponsor: Foundation for Science and Technology (FCT) ; Portugal ; Wellcome Trust ; University of Oxford
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available