Brain Circuits for Cognitive Control

As humans, our ability to cognitively adapt to change in our environment allows us to think outside the box and find solutions to complex problems. However, we tend take the power of the 'mind' for granted, rarely appreciating its capacity for flexibility until we observe the devastating effects of cognitive inflexibility that occur from both psychiatric and neurological disorders. Currently, cognitive enhancing therapeutics for neurological disorders remain elusive. Ultimately, it is our understanding of how the networks of interconnecting brain regions coordinate complex cognitive functions that will enable us to develop solutions to restore that ability to adapt.

Neuronal integration in the cerebral cortex remains important for cognitive functions such as attention and perception, whereas, the thalamus relays sensory and motor information. The thalamic reticular nucleus has been called the "gatekeeper" of thalamo-cortical and cortico-thalamic transmissions (Crick., 1984, PNAS, 81, 4586-4590). As cognitive flexibility is often explored through the lens of attentional set-shifting - the ability to form and adapt perceptual attentional predispositions when learning about complex stimuli, the thalamic reticular nucleus provides an exciting target for research.

The research undertaken will have two main aims. Firstly, we will aim to explore the thalamic reticular nucleus' contributions to the processes underlying attentional set-formation and set-shifting in rats. The results of our findings will inform our second aim - to develop, assess and validate potential therapeutic interventions in the rat that may be translated to a clinical setting.
Rats, like humans, have the ability to form attentional sets when learning about compound stimuli with multiple 'aspects' - or dimensions - that can be predictive of an outcome such as reward. This ability, therefore can be used to investigate behavioural flexibility and make inferences about the cognitive processes involved in the various components of the task - set-formation, set-shifting as one measure of flexibility - and reversal learning as another. This research will exploit a rat's natural curiosity to forage for food (digging for food reward in filled bowls), using attentional set-shifting tasks comprising a series of two-choice discriminations. The rats will be encouraged to identify a locus of interest (the dimension relevant to finding reward) from compound stimuli and then alter their attention through intradimensional learning and then extradimensional shifting, whilst also being challenged with stages that require reversal learning (Birrell & Brown, 2000, J.Neurosci. 20:4320-4324; Tait et al., 2018, Neurosci.Biobehav.Rev 89:72-84). Pharmacogenetics will allow the manipulation of brain circuitry in order to map the thalamic reticular nucleus' involvement in cognitive function in the behaving rats. Surgical administration of 'designer receptors' via viral vectors to the region of interest will permit the administration designer drugs to temporarily and reversibly 'switch off' regions of interest. This will allow the direct mapping of specific brain regions and their role in cognitive function.

The overall aim of the research will be to gain further insight into the thalamic reticular nucleus' role in modulating thalamo-cortical and cortico-thalamic inputs, and to assess potential targets for therapeutic interventions that may provide novel treatments for neurological disorders where sensory mediated attention is impaired.