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The role of ventrolateral prefrontal cortex in performance of spatial self-ordered response sequences in the marmoset



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Axelsson, Sebastian Folke Amandus 


The ventrolateral prefrontal cortex (vlPFC) in primates plays an important role in cognitive control and working memory, but as argued in the Introduction its contribution to those aspects of goal-directed behaviour such as planning and executing spatial response sequences requires further analysis, using more refined methods than have been employed hitherto. These studies investigated the role of vlPFC in performance of self-ordered response sequences using intra-cerebral microinfusions of specific pharmacologic agents in the common marmoset. Following a description of the necessary methodology, including behavioural training and surgical details (Chapter 2), a causal role for vlPFC in performance of spatial-self ordered sequences was confirmed in Chapter 3 by demonstrating that local inactivation of vlPFC using muscimol/baclofen infusions impairs sequencing. This effect was shown to be selective to performance of sequences that varied spatially from trial to trial; thus, no effects of vlPFC inactivation were observed for performance of a fixed response sequence. Once animals could learn a heuristical strategy for a self-ordered fixed sequence, vlPFC inactivation no longer impaired performance. Chapter 4 investigated the effects of the chemical neuromodulation of vlPFC on self-ordered sequencing using microinfusions of dopamine receptor D2 antagonist, sulpiride, and 5HT2A receptor antagonist, M100907 on performance of variable sequences. These drugs produced contrasting, dose-dependent impairments. M100907 impaired accuracy, while sulpiride impaired error correction. Chapter 5 studied effects of blocking glutamatergic receptors in a region of the caudate nucleus to which the vlPFC projects, but no significant effects on sequencing accuracy were observed, although there were large effects on perseverative errors in 2 out of 3 animals. The findings are discussed in Chapter 6 in terms of the functioning of the vlPFC and its possible role in controlling flexible response sequencing and working memory. The findings are shown to be of relevance for psychiatric disorders such as obsessive compulsive disorder (OCD) and schizophrenia, which show functional dysconnectivity of the vlPFC in association with response sequencing impairments.





Robbins, Trevor


Behavioral Neuroscience, Marmoset, Ventrolateral Prefrontal cortex, Self-ordered Sequencing


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Wellcome Trust (104631/Z/14/Z)