Cellular Mechanisms of State-Dependent Processing in Visual Cortex

Cellular mechanisms of state-dependent processing in visual cortex Current understanding of neuronal mechanisms mediating processing of visual information and visual perception is largely based on results from experiments on either anesthetized or awake and attentive brains. However, these two states represent two extremes on a continuum of states of alertness, and it is known that both humans and animals perceive and respond to stimuli when non-attentive, nonalert and even during light sleep. Indeed, recent studies in awake mice and rabbits revealed that transitions between alert and nonalert states dramatically change the operation of thalamic and cortical neurons along the visual pathway. However, we have a limited knowledge of changes of synaptic inputs, receptive fields and response properties of different types of cortical neurons over a broad range of states, the cellular mechanisms that drive these state- dependent changes, and how these state-dependent changes affect cortical processing of visual information. To address these gaps in our knowledge, we will exploit advantages of the visual system of rabbit, an experimental animal that can sit quietly for hours and exhibits very limited eye movements while spontaneously and naturally transitioning between alert, nonalert/drowsy and sleep states. We will make intracellular recordings from visual cortex (V1) neurons and extracellular recordings from neurons in the visual thalamus (LGN) in retinotopically aligned regions, in chronic experiments, while drug-free subjects transition between different brain states. We will (a) identify different types of cortical projection neurons and interneurons in different cortical layers electrophysiologically and using antidromic and ortodromic microstimulation in different brain structures; (b) characterize their receptive fields and response properties using a battery of visual stimuli; (c) assess the contribution of excitation and inhibition in neuronal responses, and characterize single-unit computations by analyzing the transformation of subthreshold activity into spike trains during responses to visual stimuli and injection of fluctuating currents; (d) rigorously quantify each brain state and transition between them using their characteristic signatures in the EEG recorded in the hippocampus and neocortex. These experiments will provide unique data on how thalamic inputs, visual responses and receptive fields in cortical neurons of different types change over a broad range of brain states, and investigate mechanisms of this state-dependence in terms of changes of synaptic inputs, single-unit computations, and excitation/inhibition balance. Results of the proposed research will help to achieve the next level of understanding of how brain state affects visual processing and visual perception. According to the National Highway Traffic Safety Administration, more than 1,550 people are killed and over 71,000 are injured each year in accidents caused by decreased attention and drowsiness. The proposed work will lead to a better understanding of state-dependence of visual processing and will inform further research and development of tools for detection of decreased attention and prevention of "drowsy driving" accidents. It will also inform further research into cognitive disorders associated with deficits in perception caused by impaired attention and/or dysfunction of mechanisms regulating wake-sleep cycle.