Stefano Panzeri - US grants

Project Summary To survive, organisms must both accurately represent stimuli in the outside world, and use that representation to generate beneficial behavioral actions. Historically, these two processes ? the mapping from stimuli to neural responses, and the mapping from neural activity to behavior ? have largely been treated separately. Of the two, the former has received the most attention. Often referred to as the ?neural coding problem,? its goal is to determine which features of neural activity carry information about external stimuli. This approach has led to many empirical and theoretical proposals about the spatial and temporal features of neural population activity, or ?neural codes,? that represent sensory information. However, there is still no consensus about the neural code for most sensory stimuli in most areas of the nervous system. The lack of consensus arises in part because, while it is established that certain features of neural population responses carry information about specific stimuli, it is unclear whether the brain uses (?reads?) the information in these features to form sensory perceptions. We have developed a theoretical framework, based on the intersection of coding and readout, to approach this problem. Experimentally informing this framework requires manipulating patterns of neuronal activity based on, and at the same spatiotemporal scale as, their natural firing patterns during sensory perception. This work must be done in behaving animals because it is essential to know which neural codes guide behavioral decisions. In the first phase of this project (funded by the BRAIN Initiative), we developed the technology necessary for realizing this goal. In the present proposal, we will extend our patterned neuronal stimulation technology and apply it to answer long-standing questions about neural coding and readout in the visual, olfactory, and auditory systems. We will pioneer the capacity to determine which neurons within a network are encoding behaviorally relevant information, and also to determine the extent to which temporal patterns of those neurons? activity are being used to guide behavior. Finally, we will study these neural coding principles across changes in behavioral state and during learning to determine how internal context and past experience shape coding and readout. The contributions of the proposed work will be three-fold. First, we will provide the neuroscience community with the tools needed to test theories of how neural populations encode and decode information throughout the brain. Second, we will reveal fundamental principles of spatiotemporal neural coding and readout in the visual, olfactory, and auditory systems of behaving animals. And third, our unifying theoretical framework for cracking neural codes will allow the broader neuroscience community to resolve ongoing debates regarding neural coding that have been previously stalemated by considering only half of the coding/readout problem.

Project Summary Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of populations of neurons at different levels of information processing? and 2) what features of this activity are read at the next levels of neural processing to guide behavior? The first question has been the subject of a large body of work across different sensory stimuli. To answer the second question, one needs to establish a causal link between neuronal activity and behavior. In many systems sensory information is represented by complex spatiotemporal patterns of neuronal activity. Novel recording and stimulating technology will soon allow the precise temporal control of hundreds and thousands of individual neurons, however, conceptual approaches of finding relevance of different spatiotemporal features of neural code still lag behind. To develop a new approach we chose the mammalian olfaction as a model system, because odor stimuli evoke complex patterns of glomerular activity with spatial and temporal scales fully compatible with existing imaging and pattern stimulation technologies. In addition, the accessibility of the cells in the next processing level, the mitral/tufted cells which get input from olfactory glomeruli and transmit the signal to higher brain areas, allows a systematic study of encoding different features of neural activity with known behavioral relevance. We propose a novel approach to map spatiotemporal code features to neural and perceptual spaces. First, we substitute sensory-driven neural activation by artificial and fully parametrized optogenetic pattern stimulation. By varying the parameters of such stimulation and recording the behavioral outcomes of the stimulation, we will build a detailed empirically-validated mathematical model of the relevance of different features of neural activity. Then we will test this model for natural odor stimuli, and explore how these features are processed and encoded by the next level of processing. Successful execution of the project will produce the first (to our knowledge) causally validated model for behavioral relevance of a distributed neural code. It will shine light on long standing questions in olfactory processing, approaching the olfactory code from the perspective of its behavioral relevance. The proposed approach can be further applied to different neural systems using multi-neuronal recording and stimulation techniques.