Abstract

Perceptual sensitivity varies from moment to moment. One potential source of this variability is spontaneous fluctuations in neural sensitivity. Using newly developed techniques to characterize the moment-to-moment dynamics of noisy multi-electrode data, we find that spontaneous cortical activity is organized into traveling waves that traverse visual cortex several times per second. Recording in Area MT of the common marmoset, we find that these intrinsic traveling waves (iTWs) regulate both the gain of the stimulus-evoked spiking response and the monkey’s perceptual sensitivity. In monkeys trained to detect faint visual targets, the iTW state prior to target onset predicts the magnitude of target-evoked neural response and the likelihood that the monkey will detect the target. A large-scale spiking network model with conductance-based synapses recapitulates the properties of iTWs measured in vivo. The model shows that iTWs naturally emerge from the delays that occur as action potentials traverse unmyelinated horizontal fibers. The model predicts that iTWs are sparse, in the sense that only a small fraction of the neural population participates in any individual iTW. As a result, iTWs can occur without inducing correlated variability, which we have found, in separate experiments, can impair sensory discrimination. We thus refer to the model as the sparse-wave model of iTWs. The model also predicts that iTWs fall into feature-selective motifs whose selectivity stems from the horizontal fibers that preferentially connect similarly tuned feature domains. Consistent with this prediction, we find distinct clusters of iTW motifs. Some motifs modulate neural activity and perceptual sensitivity in a feature-selective manner. Taken together, these findings lead to the conclusion that traveling waves strongly modulate neural and perceptual sensitivity, in a feature-selective manner. These findings are consistent with studies of traveling waves in the motor system, suggesting that iTWs may represent a brain-wide computational principle.

Related Literature

Davis, W., Muller, L., Martinez-Trujillo, J., Sejnowski, T., Reynolds, J.H. Spontaneous travelling cortical waves gate perception in behaving primates (2020) Nature. DOI: https://www.nature.com/articles/ s41586-020-2802-y.

Davis, Z.W., Benigno, G.B., Fletterman, C., Desbordes, T., Steward, C., Sejnowski, T.J., Reynolds, J.H., Muller, L. Spontaneous traveling waves naturally emerge from horizontal fiber time delays and travel through locally asynchronous-irregular states. (2021) Nature Communications. 12(1):6057. DOI: 10.1038/s41467-021-26175-1.

Davis, Z.W., Muller, L., Reynolds, J. Spontaneous Spiking Is Governed By Broadband Fluctuations. (2022) Journal of Neuroscience. DOI: 10.1523/JNEUROSCI.1899-21.2022.

Abstract

Abstract

Abnormal tau, amyloid beta, and TDP-43 proteins forms aggregates in disease-affected neurons in patients with Alzheimer’s Disease and related dementia. Mutations in the genes encoding these aggregating proteins can cause inherited dementia in families. By expressing human mutant tau, and TDP-43 protein in C. elegans neurons, we have modelled aspects of dementia pathobiology. This animal model exhibits severe motor dysfunction, progressive neurodegeneration, and accumulation of abnormally modified aggregated proteins. To identify genes regulating proteotoxicity C. elegans, we have surveyed all C. elegans genes to find several that participate in neurodegeneration. We have leveraged these findings to explore new molecular mechanisms contributing to neurodegeneration in the mammalian brain.