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Title: Investigating the role of the rat medial prefrontal cortex in executive function
Author: Benn , Abigail
ISNI:       0000 0004 5920 0787
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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The aim of this thesis was to contribute to the understanding of the role of the mPFC in executive function using different methodologies. Pharmacological, electrical stimulation, and optogenetic approaches, were used to gain temporal precision and /or cell-type specificity, to investigate the role of the mPFC in visuo-spatial attention, impulse control, and recognition memory. Visuo-spatial attention and impulse control were investigated through systemic and targeted glutamatergic manipulations. These were performed in animals trained in a non-paced variable-inter-trial interval (VITI) version of the 5-Choice serial reaction time task (5-CSRTT). Animals trained in this task were less sensitive to attentional disruption, but not impulse control via NMDA antagonism, due to less reliance on behavioural strategies for optimal performance than in the standard version of the 5- CSRTT. Inconsistent findings across different NMDA antagonists were found, despite their interchangeable use for modelling hypo-glutamatergic function. Manipulations to glutamatergic function via mGluR revealed a role for the mPFC, and pre-synaptic mGluR7, but not more widely located mGluR2/3, in visuo-spatial attention. Electrical stimulation targeted to the mPFC was used to deliver temporally controlled and continuous stimulation to investigate the effects of stimulation frequency in the 5- CSRTT. Electlical stimulation caused neuronal activation within the mPFC but had no effect on visuo-spatial attention or impulse control, irrespective of the frequency used. High frequency stimulation of the mPFC showed a tendency to disrupt goal-directed behaviour, with disruptive effects more apparent with temporally controlled stimulation rather than continuous stimulation. Theta stimulation did not remediate performance deficits or disrupt baseline performance. A lenti-viral vector containing channel rhodopsin under the control of a glutamatergic specific promoter (CaMKII) was used to investigate the effects of glutamatergic neuronal activity, within the mPFC, on recognition memory. Optogenetic stimulation during the delay phase of the object-in-place task, induced neuronal activation of mPFC glutamatergic neurones, and enhanced recognition memory performance in a prefrontal dependent task. The data also confirmed a role for the mPFC for the integration of spatial and object information in associative recognition memory, but not for single item discrimination. In conclusion these results extend previous findings based historically on lesions and pharmacology, and show that glutamatergic specific manipulations to the mPFC affects prefrontal function depending on the type of manipulation used. These manipulations can also enhance performance under certain conditions. This thesis highlights the necessity for multi-dimensional approaches in behavioural research, as the techniques used here, as well as more traditional methods, give unique insights into prefrontal function.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available