title: Behavioural and neuronal correlates of spatial attention in the mouse whisker system
Creators: name: Dyce, Guthrie
Publisher: name: The Australian National University
Year: 2024

description: In any given instant, our senses are bombarded by a surplus of information. Transforming this information into adaptive behaviour is imperative to the survival of all animals. The faculty of selective attention, which performs this function, exhibits both conceptual and neurophysiological parallels to the process of decision-making, except that it operates in information space. Decades of research have produced a rich literature on the behavioural and neuronal correlates of selective attention. Yet the precise microcircuitry and molecular mechanisms of attention remain to be elucidated. Mice represent an attractive model organism within which to study the mechanisms of attention owing to the availability of gene technologies designed for their species. However, attention is traditionally studied in the more complex brain of primates as studying attention in mice is experimentally challenging. The current thesis aims to investigate the behavioural and neuronal correlates of spatial attention using whisker touch as an ecologically relevant, structurally elegant, and functionally efficient model sensory system. I begin this thesis with a literature review on spatial attention and its neuronal correlates in primates and mice (Chapter 1). In Chapter 2, I explore a number of head-fixed experimental approaches to studying spatial attention in mice. I document the efficacy and limitations of two approaches (spatial cueing and spatial blocking) before presenting a novel approach that uses a stimulus-reward contingency as an ecologically relevant manipulation to induce spatial attention. Consistent with prior research, my results suggest that spatial cueing paradigms, directly borrowed from primate literature, can be effective in recruiting attention from rodents. However, these paradigms require extensive training if mice are to learn the task. The blocked spatial manipulation of target-stimulus probability is more effective than spatial cueing, yet it is limited by the occurrence of systematic spatial biases in mice. I then design and demonstrate the efficacy of an original, simplified behavioural paradigm for studying spatial attention in the whisker system of mice by directly manipulating stimulus-reward contingencies ("ecological prioritisation"). Chapter 3 optimises this behavioural paradigm, demonstrating that it reliably elicits rapid and spatially selective attentional engagement to the rewarded stimulus. Trained mice exhibited spatial attention in the form of elevated hit rates and perceptual sensitivities. In Chapter 4, I document extracellular recordings of neuronal activity in six behaving mice (n = 1461 responsive units) to demonstrate that neurons in the primary vibrissal cortex (vS1) exhibit spatially selective attentional gain modulation. Neuronal activity in vS1 increased with spatial attention, but not with spatially non-specific behavioural state. Spatial attention increased both pre-stimulus and evoked neuronal activity, although the greatest attentional gain modulation was observed in later activity (200-600 ms). The same time-course was present in the perceptual sensitivities to vibrissal stimuli. My data thus dissociates spatially non-specific behavioural state from spatial attention in the whisker system. In Chapter 5, I demonstrate that the frequency tagging approach which has been applied effectively to the macroscopic study of attention in humans can be usefully leveraged in the study of spatial attention at the neuronal level in mice. Finally, in Chapter 6, I provide a general discussion regarding the advantages of this ecological prioritisation paradigm and the identified neuronal correlates of spatial attention in the primary vibrissal cortex of mice. These experiments further validate the mouse as a model organism for studying spatial attention and lay a foundation for elucidating its mechanisms at the cellular and circuit level.