Perception and cognition rely on processing performed in a distributed network of cortical areas. These areas communicate through feedforward, lateral, and feedback corticocortical connections. Our long-term goal is to understand the function of corticocortical feedback circuitry, which has been proposed to underlie a number of functions but remains poorly understood. Previous work has attempted to elucidate the function of feedback by reversibly inactivating higher cortex with either pharmacological or cooling methods, and measuring effects in single neurons in lower cortex. While important, this previous work suffers from critical limitations. Inactivation has limited specificity, usually involving large swaths of cortex and thus neurons with different functional properties. Measuring the consequences on lower cortex using only single neuron firing rates would fail to capture any effects of feedback on network coordination, which much recent work suggests may be central to cortical function. Previous studies have also often neglected to determine the laminar location of their recordings: feedback connections are laminar-specific, thus their effects may vary through the targeted cortical columns. In this study we will use optogenetic methods, combined with multielectrode neurophysiology, to elucidate the function of corticocortical feedback in the macaque visual cortex. Guided by preliminary results, our working hypothesis is that these connections are functionally-specific and alter the coordination among targeted neurons. This coordination may in turn enhance the coupling to downstream target networks.
In specific aim 1, we will test how optogenetic recruitment and silencing of small populations of neurons in cortical area V2 affects neuronal responsivity and tuning across layers of primary visual cortex (V1). Using the local field potential and small ensembles of simultaneously-recorded neurons, we will also measure how network coordination is affected by manipulating feedback. We will measure effects both in the presence and absence of visual drive, to determine how the effects of feedback depend on network state. Finally, we will evaluate how the effects of feedback depend on the functional and retinotopic alignment of the stimulation and recording site.
In specific aim 2, we will use planar electrode arrays to explore in detail the effects of feedback on the coordination of large neuronal ensembles in the superficial layers of V1, the primary output population projecting to higher visual cortex. Our experiments will provide an unprecedented view of how feedback modulates V1, how these effects depend on the relationship between the functional properties of the source and target neurons, and how feedback interacts with bottom-up sensory information. This work will form a solid basis for future work in which we will use optogenetic methods to manipulate circuits in a perceptual decision making paradigm. Disrupted corticocortical signaling has been implicating in a number of disorders, including schizophrenia and autism. By furthering our understanding of the signals provided from higher to lower cortex, our results will contribute to improved diagnosis and treatment of such disorders.

Public Health Relevance

The communication between distinct areas of the cerebral cortex is central to cortical function, including perception and cognition. It is therefore not surprising that disrupted or altered corticocortical signaling has been implicated in a number of disorders, including a strong link to schizophrenia and autism. By furthering our understanding of feedback circuitry, we expect to provide important information about how higher networks modulate the function of lower ones, and how disruption of this modulation contributes to disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Flanders, Martha C
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Albert Einstein College of Medicine, Inc
United States
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