| Ամփոփում: | To thrive in an ever-changing world, animals must rapidly and flexibly adapt their behaviour according to their needs. Some problems require an initial period of learning through trial and error; others can be quickly solved by generalising and integrating information from previous experiences. In this thesis, I explore anatomical and functional features of the brain system that support these learning and decision-making processes. In particular, I focus on the role of the orbitofrontal cortex (OFC) and midbrain dopaminergic projections which play a critical role in sustaining flexible behaviour. Behavioural research suggests the OFC is functionally heterogeneous along its medial–lateral and anterior–posterior axes. In Chapter 3, I investigated whether this functional heterogeneity is underpinned by differences in anatomical connectivity by simultaneously characterising the input patterns into the anterior lateral, posterior lateral, and posterior ventral portions of the rat OFC. The results show that these OFC subdivisions receive distinct and topographically organised inputs from various thalamic nuclei, basolateral amygdala, and various cortical areas. Learning and behavioural adaptation are particularly important when expectations are not met, eliciting reward prediction errors (RPEs) –the difference between expected and actual outcomes. In the brain, the encoding of these teaching signals has long been linked with the activity of dopamine neurons. However, there has been no direct demonstration between the behaviourally derived haemodynamic signatures of RPEs measured with functional magnetic resonance imaging (fMRI) and dopamine release. Thus, to establish the contribution of dopamine to haemodynamic signatures of RPEs encoding, Chapter 4 combined recordings of haemodynamic signals in the OFC and nucleus accumbens (NAc) with lesioning of NAc dopaminergic inputs. OFC responses were surprisingly larger after lesioning of dopaminergic inputs to NAc, suggesting a potential balance between the activity of the two regions. Dopaminergic signalling dysregulation is thought to drive the neuronal mechanisms underlying psychotic symptoms such as delusions through disruption of RPEs encoding in frontostriatal circuits. Chapter 5 shows that maladaptive behaviour during amphetamine-induced hyperdopaminergic states is linked to disruption of NAc haemodynamic responses. Then, in Chapter 6, I describe the development of a novel rodent behavioural paradigm in which rats must develop a model of the world to maximise reward, for investigating how the brain encodes information during generalisation. Chapter 7 summarises the findings from the previous chapters and discusses their implications for our understanding of how the brain encodes information for supporting flexible behaviour.
|
|---|