Traveling Waves in Neocortical Circuits: Mechanisms, Computational Roles in Sensory Processing, and Impact on Sensory Perception - PROJECT SUMMARY/ABSTRACT An important longstanding goal in neuroscience research is to understand how large-scale spatiotemporal patterns of neural activity emerge in the brain and whether they have a direct role in shaping the brain’s computational processes and thereby mammalian behavior. Notably, traveling waves of neural activity have been implicated in sensory, cognitive, and motor behaviors, and this team recently found that intrinsic traveling waves (iTWs) in visual cortical areas predict the magnitude of evoked spiking activity and visual perceptual sensitivity in awake, behaving non-human primates. However, it remains unclear whether iTWs reflect an underlying fundamental mechanism of cortical function or whether they might simply be epiphenomenal. This project will examine the role of neocortical iTWs in visual perception and is guided by a theoretical model of iTW activity that makes specific testable and falsifiable predictions about the mechanisms that give rise to the spatiotemporal features of iTWs and their roles in sensory behavior. The model is based on a network of spiking neurons and predicts that iTWs emerge from the anatomical organization of horizontal cortical fibers and result in shifts in the balance of excitatory (E) and inhibitory (I) population activity that travel as waves, The model further predicts that iTWs are retinotopically coordinated across visual cortical areas, and that this coordination is the mechanism by which iTWs improve perception. However, these predictions could be wrong. Empirical tests of the model’s predictions will require activity measurements from specific neuron-types, across wide fields- of-view, and with excellent spatial and temporal resolution in awake behaving animals. To perform such measurements, the team recently invented several new technologies: (1) genetically encoded fluorescent voltage indicators (GEVIs) that they will target to specific E or I neural populations; (2) a custom-built dual-color fluorescence mesoscope to track the subthreshold population voltage dynamics of 2 neuron-types at once, across a 8-mm field-of-view spanning multiple cortical areas in marmoset and mouse cortex; (3) transparent electrode arrays that allow measurements of LFPs to be performed across the cortex concurrently with voltage imaging studies of E and I population activity; (4) transparent laminar electrode arrays to measure the spiking activity of cells across the different cortical layers. By combining the use of these four innovations in marmosets and mice performing a visual detection task, the team will test the predictions of the theoretical model and learn how different cortical neuron-types impact iTW dynamics and perceptual sensitivity. Aim 1 tests the hypothesis that E/I population activity travels as iTWs in mice and marmosets. Aim 2 tests the prediction that iTWs are coordinated retinotopically across cortical areas, and that this coordination enhances perceptual sensitivity. Aim 3 will account mechanistically for the results of Aims 1 and 2 in a theoretically grounded spiking network model. Overall, by using innovative new technologies this interdisciplinary team will provide key insights into longstanding conceptual issues of profound importance to brain research.
