Two individuals presented with similar sensory input may process the incoming material in very different ways depending on their level of engagement with the presented information. However, it is not understood how engagement (defined as non-selective attention to sensory input) exerts such a strong influence on neural processing. The goal of the proposed research is to investigate the influence of engagement on cortical processing of visual input using a mouse model. First, we will establish an experimental preparation for measuring the activity of primary visual cortical (V1) neurons in awake, head-fixed mice performing a behavioral task (Aim 1). Neural activity will be measured by 2-photon imaging of visual cortical neurons expressing a virally delivered genetically encoded calcium indicator (GCaMP5) while the mouse performs a demanding orientation discrimination task. The response apparatus will be withdrawn in alternating blocks, allowing comparison of responses during engaged versus passive viewing. Next, we will characterize the effects of engagement on different classes of neurons in V1 using transgenic mouse lines that express red fluorescent protein (TdTomato) in cell types of interest (specifically, parvalbumin-positive and somatostatin- positive interneurons;
Aim 2). Genetic identification of interneuron subtypes will allow us to dissect the effect of engagement on specific components of the cortical circuitry. Finally, we will investigate the impact of engagement on sensory processing in higher visual cortical regions beyond V1 (Aim 3). For these experiments, secondary visual areas LM (lateromedial), AL (anterolateral), and PM (posteromedial) will be identified using anterograde tracers and imaged using GCaMP5. Responses in secondary visual areas will be imaged to determine whether engagement enhances the propagation of sensory information more broadly throughout the visual cortical hierarchy. Taken together, this work will have important implications for understanding the influence of behavioral engagement on sensory processing in the neocortex, and reveal fundamental mechanisms underlying disorders of cognition that afflict engagement and attention.
Deficits in the ability to properly engage with the sensory environment have been described in a number of neurological disorders, including attention deficit hyperactivity disorder (ADHD). In this project, we hope to establish a basic scientific understanding of how engagement influences neural processing in sensory cortex. We also hope to establish a model system by which we can attempt to experimentally improve the level engagement by pharmacological or optogenetic manipulations, and thereby generate potential therapeutic approaches for treating dysfunction of sensory engagement observed in common neurological disorders.