Midbrain circuits for perceptual decision-making

This $11,353,776 cooperative agreement from the National Institutes of Health's National Institute of Neurological Disorders and Stroke will fund research into midbrain circuits for perceptual decision-making. The University of Virginia will lead a team investigating how the superior colliculus participates in visual decision-making processes. Researchers will conduct psychophysical experiments in mice and tree shrews to assess perceptual decision-making, and fit behavioral data with computational models. Calcium imaging and electrophysiological recording will determine neuronal activity in target cell types during tasks. Optogenetics will reveal the roles of these cells by silencing them during experiments. Viral tracing, microscopy, and optogenetics-assisted recording will investigate intrinsic and extrinsic circuits linking the cells. Subawards of $1,000,000 each to the University of Louisville and the University of Washington will support participation in the circuit dissection and psychophysics experiments, respectively. This research aims to further understanding of synapse to circuit mechanisms underlying perceptual decisions, as funded under the NIH's Extramural Research Programs in the Neurosciences and Neurological Disorders program.

Abstract

Perceptual decision-making is a fundamental cognitive ability that is vital to healthy, daily functioning and is impaired in many diseases. Although many brain regions are known to be involved, there is no clear brain-wide model of how perceptual decisions are formed and executed and the underlying circuit mechanisms are still largely unknown. Here, a team of investigators propose a series of experiments that will use behavioral measures, imaging, physiology, circuit dissection, and computational modeling to study how the midbrain superior colliculus (SC) participates in visual decision-making. Specifically, this new team of investigators will probe the contribution of two SC neuronal cell types, wide field vertical (WFV) cells in the visuosensory layers and predorsal bundle (PDB) cells in the motor layers. These experiments will be done in mice and tree shrews, to reveal the underlying circuits and computational principles across species and to lay the foundation for future experiments designed to dissect decision-making circuits in primates. In aim 1, the investigators will establish and perform psychophysical experiments to assess perceptual decision-making in both species. The behavioral data will be fitted with computational models to arbitrate between different theories of decision-making. In aim 2, two photon calcium imaging and/or physiological recording will be performed in mice and tree shrews to determine the activity of WFV and PDB neurons during the psychophysical measures established in aim 1. In addition, WFV and PDB neurons will be silenced optogenetically during the behavioral tasks to reveal their specific roles in decision-making. In aim 3, the investigators will use intersectional monosynaptic viral tracing techniques, multiplexed peroxidase labeling for confocal and ultrastructural analysis of synaptic connections and and optogenetics-assisted brain slice recording to investigate the intrinsic and extrinsic circuits that link WFV and PDB cells. Together, these experiments will generate novel knowledge of the synapse to circuit mechanisms underlying perceptual decision-making, and provide technical and theoretical foundations for future mechanistic studies of cognitive function in higher mammalian species directly relevant to humans.