Attention regulation and behavioural flexibility in rats with relevance to schizophrenia

Abstract

Schizophrenia is a neuropsychological disorder in which the neural systems which regulate attention allocation, primarily the dorsolateral prefrontal cortex, are dysfunctional, resulting in deficient gating of attention to irrelevant inputs from the environment. This sensory processing dysfunction hinders goal-directed behaviour to the extent that the subsequent cognitive deficits of schizophrenia prevent many chronic patients from leading normal lives. It is the onus of neuroscience to understand the nature of deficits induced by the disorder, thus providing target mechanisms for remediation of those deficits in patients. To accomplish this, manipulations in rats with relevance to schizophrenia are examined in assays with translation to human neurobiology and behaviour. In this thesis, three manipulations with relevance to schizophrenia, were examined for attentional regulation in the attentional set-shifting task, and similar assays, to determine how different forms of schizophrenia-related pathology influence attentional regulation and behavioural flexibility. The foremost findings of the experiments herein were that manipulations inducing schizophrenia-related neurobiology, resulted in impaired performance in extradimensional set-shifting and reversal learning. These deficits were found following: acute inhibition of the mPFC in adult rats, in adult rats who had been exposed to a glutamate receptor antagonist during the neonatal period of development, and/or in adult rats who had gestational disruption of neuron proliferation. Across all three manipulations, a clear behavioural pattern of deficient sensory gating, evidenced by responding to irrelevant stimuli during the set-shifting task was found. These findings suggest that at the core of the cognitive deficits in schizophrenia is the ‘loosening of associations’ such that patients suffer the inability to regulate attention, and limit sensory processing to relevant information. The subsequent aberrant learning about irrelevant information then impairs performance during goal-directed behaviours.