Sensory processing is a way to understand neural circuits and their functions during behavior. Behavioral context strongly affects sensory processing. For example, a brief visual stimulus is easier to detect if it appears in a predictable spatial location. Attention to visual space strongly enhances neural and behavioral responses to stimuli in those locations, but the detailed neural mechanisms producing these effects remain unknown. This is largely because we lack the ability to measure specific neurons, circuits, and synapses in real-time during behavior that elicits visual spatial attention. We are uniquely positioned to bridge this critical knowledge gap with an innovative combination of cell-type specific optogenetics, multi-site silicon electrode recordings, and whole-cell patch-clamp recordings in mouse primary visual cortex (V1) during a well-defined visual spatial attention behavior. This innovative combination of techniques will enable us to 1) determine response (gain) modulation in defined excitatory and inhibitory neurons during spatial attention; 2) determine gain modulation across cortical layers during spatial attention; 3) determine synaptic mechanisms of gain modulation during spatial attention SIGNIFICANCE. This project will meet a significant need to understand how an internal cognitive state—attention—exerts its effects across synaptic, cellular, network, and behavioral levels. Establishing a biophysical basis for attention and sensory processing will provide greater understanding of neurological disorders characterized by deficits of attention and sensory perception, such as schizophrenia and autism. INNOVATION. This work provides technical innovation by combining multiple scales of measurement from specific neural circuits during a well-controlled sensory behavior that elicits spatial attention. We will combine high-density local field potential and action potential measurements at population level, patch-clamp measurements from cortical and thalamic circuits at the synaptic level, and cell-type specific optogenetics. We provide conceptual innovation by defining how an internal cognitive factor like attention modulates sensory signals in defined circuits across network and synaptic levels.

The control of sensory processing by attention is critical for normal behavior. Impairments in sensory processing and attention characterize many debilitating neurological conditions such as schizophrenia, dementia, and autism spectrum disorders. We lack effective treatments for such disorders partly because we have scarce knowledge about the basic underlying neural mechanisms.