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.

Grant Number: 3R01EY034503-02S1
NIH Institute/Center: NIH
Principal Investigator: Yulia Bereshpolova