Sensory perception is fundamentally limited by the coding accuracy of sensory neural ensembles. Although a substantial body of work suggests that populations of sensory neurons exhibit correlated fluctuations that may bound the precision of neural coding, the extent to which these fluctuations extend across multiple cortical areas and interact with sensory coding during active animal behavior remain poorly understood. To examine the impact of correlated fluctuations on information coding and communication across sensory cortical areas, we imaged the Ca2+ activity of > 21,000 individual neurons across 11 neocortical areas in mice performing a Go/No-Go visual decision-making task. Multiple neocortical areas accurately encoded the visual stimulus, as well as the animal's decision to respond. Our analysis also revealed positively correlated noise fluctuations across neural populations in multiple neocortical areas. The mean strength of these noise correlations varied as a function of time across the visual stimulus presentation, delay, and response periods of our decision-making assay. Notably, sensory cortical neurons generally exhibited noise fluctuations that were more positively correlated at the start of visual stimulation, but then less so as a decision-making trial proceeded. Our results reveal that 60% of the total power of cortical variability stems from correlated fluctuations of neural populations spanning multiple distinct cortical areas. The strongest cortical fluctuation was a decision-coding activity mode that encompassed all brain areas under observation. We also found several fluctuation modes that encoded visual stimulus information but were shared across fewer brain areas. Overall, our analyses suggest that information regarding sensory stimuli and perceptual decisions are processed and shared between cortical areas through mutually non-interfering orthogonal channels. The timing of informative activity in these channels suggests that sensory information is first processed through intercommunications between multiple sensory areas, followed by a propagation of the final decision to all cortical areas involved.

In neurophysiology, the emphasis has been on single-unit studies for a quarter century, since the sensory work by Lettwin and coworkers and by Hubel and Wiesel, the cen tral work by Mountcastle, the motor work by the late Evarts, and so on. In recent years, however, field potentials - and a more global approach general ly - have been receiving renewed and increasing attention. This is a result of new findings made possible by technical and conceptual advances and by the confirma tion and augmentation of earlier findings that were widely ignored for being contro versial or inexplicable. To survey the state of this active field, a conference was held in West Berlin in August 1985 that attempted to cover all of the new approaches to the study of brain function. The approaches and emphases were very varied: basic and applied, electric and magnetic, EEG and EP/ERP, connectionistic and field, global and local fields, surface and multielectrode, low frequencies and high frequencies, linear and non linear. The conference comprised sessions of invited lectures, a panel session of seven speakers on "How brains may work," and a concluding survey of relevant methodologies. The conference showed that the combination of concepts, methods, and results could open up new important vistas in brain research. Included here are the proceedings of the conference, updated and revised by the authors. Several attendees who did not present papers at the conference later ac cepted my invitation to write chapters for the book.

Perceptual decision-making is an important and experimentally tractable paradigm for uncovering general principles of neural information processing and cognitive function. While the process of mapping sensory stimuli onto motor actions may appear to be simple, its neural underpinnings are poorly understood. The goal of this thesis is to better understand the neural mechanisms underlying perceptual decision-making by exploring three major questions: How is decision-relevant information encoded across the cortex? What cortical areas are necessary for perceptual decision-making? And finally, what neural mechanisms underlie the mapping of sensory percepts to appropriate motor outputs? We investigated the roles of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices of mice during a memory-guided visual decision task. Large-scale calcium imaging revealed that neurons in each area were heterogeneous and spanned all task epochs (stimulus, delay, response). However, information encoding was distinct across regions, with V1 encoding stimulus, fMC encoding choice, and PPC multiplexing the two variables. Optogenetic inhibition during behavior showed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus information was therefore rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution. We further investigated whether the role of PPC was specific to visual processing or to sensorimotor transformation. Using calcium imaging during both engaged behavior and passive viewing, we found that unlike V1 neurons, most PPC neurons responded exclusively during task performance, although a minority exhibited contrast-dependent visual responses. By re-training mice on a reversed task contingency, we discovered that neurons in PPC but not V1 reflected the new sensorimotor contingency. Population analyses additionally revealed that task-specific information was represented in a dynamic code in PPC but not in V1. The strong task dependence, heterogeneity, and dynamic coding of PPC activity point to a central role in sensorimotor transformation. By measuring and manipulating activity across multiple cortical regions, we have gained insight into how the cortex processes information during sensorimotor decisions, paving the way for future mechanistic studies using the mouse system.

The neocortex of awake animals displays an activated state in whichcortical activity manifests highly complex, seemingly noisybehavior. At the level of single neurons the activity is characterizedby strong subthreshold fluctuations and irregular firing at lowrate. At the network level, the activity is weakly synchronized andexhibits a chaotic dynamics. Yet, it is within this regime thatinformation is processed reliably through neural networks. This regimeis thus crucial to neural computation. In this thesis, we contributeto its understanding by investigating how the biophysical propertiesat the cellular level combined with the properties of the networkarchitecture shapes this asynchronous dynamics.This thesis builds up on the so-called mean-field models of networkdynamics, a theoretical formalism that describes population dynamicsvia a self-consistency approach. At the core of this formalism lie theneuronal transfer function: the input-output description of individualneurons. The first part of this thesis focuses on derivingbiologically-realistic neuronal transfer functions. We firstformulate a two step procedure to incorporate biological details (suchas an extended dendritic structure and the effect of various ionicchannels) into this transfer function based on experimentalcharacterizations.First, we investigated in vitro how layer V pyramidal neocorticalneurons respond to membrane potential fluctuations on a cell-by-cellbasis. We found that, not only individual neurons strongly differ interms of their excitability, but also, and unexpectedly, in theirsensitivities to fluctuations. In addition, using theoreticalmodeling, we attempted to reproduce these results. The model predictsthat heterogeneous levels of biophysical properties such as sodiuminactivation, sharpness of sodium activation and spike frequencyadaptation account for the observed diversity of firing rateresponses.Then, we studied theoretically how dendritic integration in branchedstructures shape the membrane potential fluctuations at the soma. Wefound that, depending on the type of presynaptic activity, variouscomodulations of the membrane potential fluctuations could beachieved. We showed that, when combining this observation with theheterogeneous firing responses found experimentally, individual neuronsdifferentially responded to the different types of presynapticactivities. We thus propose that, because this mechanism offers a wayto produce specific activation as a function of the input properties,biophysical heterogeneity might contribute to the encoding of the stimulusproperties during sensory processing in neural networks.The second part of this thesis investigates how circuit properties,such as recurrent connectivity and lateral connectivity, combine withbiophysical properties to impact sensory responses through effectsmediated by population dynamics.We first investigated what was the effect of a high level of ongoingdynamics (the Up-state compared to the Down-state) on the scaling ofpost-synaptic responses. We found that the competition between therecruitment within the active recurrent network (in favor of highresponses in the Up-state) and the increased conductance level due tobackground activity (in favor of reduced responses in the Up-state)predicted a non trivial stimulus-response relationship as a functionof the intensity of the stimulation. This prediction was shown toaccurately capture measurements of post-synaptic membrane potentialresponses in response to cortical, thalamic or auditory stimulation inrat auditory cortex in vivo.Finally, by taking advantage of the mean-field approach, weconstructed a tractable large-scale model of the layer II-III networkincluding the horizontal fiber network. We investigate thespatio-temporal properties of this large-scale model and we compareits predictions with voltage sensitive dye imaging in awake fixatingmonkey...

The brain produces complex patterns of activity that occur at different spatio-temporal scales. One of the fundamental questions in neuroscience is to understand how exactly these dynamics are related to brain function, for example our ability to extract and process information from the sensory periphery. This dissertation presents two distinct lines of inquiry related to different aspects of this high-level question. In the first part of the dissertation, we study the dynamics of burst suppression, a phenomenon in which brain electrical activity exhibits bistable dynamics. Burst suppression is frequently encountered in individuals who are rendered unconscious through general anesthesia and is thus a brain state associated with profound reductions in awareness and, presumably, information processing. Our primary contribution in this part of the dissertation is a new type of dynamical systems model whose analysis provides insights into the mechanistic underpinnings of burst suppression. In particular, the model yields explanations for the emergence of the characteristic two time-scales within burst suppression, and its synchronization across wide regions of the brain.The second part of the dissertation takes a different, more abstract approach to the question of multiple time-scale brain dynamics. Here, we consider how such dynamics might contribute to the process of learning in brain and brain-like networks, so as to enable neural information processing and subsequent computation. In particular, we consider the problem of optimizing information-theoretic quantities in recurrent neural networks via synaptic plasticity. In a recurrent network, such a problem is challenging since the modification of any one synapse (connection) has nontrivial dependency on the entire state of the network. This form of global learning is computationally challenging and moreover, is not plausible from a biological standpoint. In our results, we overcome these issues by deriving a local learning rule, one that modifies synapses based only on the activity of neighboring neurons. To do this, we augment from first principles the dynamics of each neuron with several auxiliary variables, each evolving at a different time-scale. The purpose of these variables is to support the estimation of global information-based quantities from local neuronal activity. It turns out that the synthesized dynamics, while providing only an approximation of the true solution, nonetheless are highly efficacious in enabling learning of representations of afferent input. Later, we generalize this framework in two ways, first to allow for goal-directed reinforcement learning and then to allow for information-based neurogenesis, the creation of neurons within a network based on task needs. Finally, the proposed learning dynamics are demonstrated on a range of canonical tasks, as well as a new application domain: the exogenous control of neural activity.

Theoretical neuroscience provides a quantitative basis for describing what nervous systems do, determining how they function, and uncovering the general principles by which they operate. This text introduces the basic mathematical and computational methods of theoretical neuroscience and presents applications in a variety of areas including vision, sensory-motor integration, development, learning, and memory. The book is divided into three parts. Part I discusses the relationship between sensory stimuli and neural responses, focusing on the representation of information by the spiking activity of neurons. Part II discusses the modeling of neurons and neural circuits on the basis of cellular and synaptic biophysics. Part III analyzes the role of plasticity in development and learning. An appendix covers the mathematical methods used, and exercises are available on the book's Web site.

This book originated at a small and informal workshop held in December of 1992 in Idyllwild, a relatively secluded resort village situated amid forests in the San Jacinto Mountains above Palm Springs in Southern California. Eighteen colleagues from a broad range of disciplines, including biophysics, electrophysiology, neuroanatomy, psychophysics, clinical studies, mathematics and computer vision, discussed 'Large Scale Models of the Brain, ' that is, theories and models that cover a broad range of phenomena, including early and late vision, various memory systems, selective attention, and the neuronal code underlying figure-ground segregation and awareness (for a brief summary of this meeting, see Stevens 1993). The bias in the selection of the speakers toward researchers in the area of visual perception reflects both the academic background of one of the organizers as well as the (relative) more mature status of vision compared with other modalities. This should not be surprising given the emphasis we humans place on'seeing' for orienting ourselves, as well as the intense scrutiny visual processes have received due to their obvious usefullness in military, industrial, and robotic applications. JMD.

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