Dynamics on the manifold: Identifying computational dynamical activity from neural population recordings

The question of how the collective activity of neural populations gives rise to complex behaviour is fundamental to neuroscience. At the core of this question lie considerations about how neural circuits can perform computations that enable sensory perception, decision making, and motor control. It is thought that such computations are implemented through the dynamical evolution of distributed activity in recurrent circuits. Thus, identifying dynamical structure in neural population activity is a key challenge towards a better understanding of neural computation. At the same time, interpreting this structure in light of the computation of interest is essential for linking the time-varying activity patterns of the neural population to ongoing computational processes. Here, we review methods that aim to quantify structure in neural population recordings through a dynamical system defined in a low-dimensional latent variable space. We discuss advantages and limitations of different modelling approaches and address future challenges for the field

Optimal Adaptation Principles In Neural Systems

Animal brains are remarkably efficient in handling complex computational tasks, which are intractable even for state-of-the-art computers. For instance, our ability to detect visual objects in the presence of substantial variability and clutter sur- passes any algorithm. This ability seems even more surprising given the noisiness and biophysical constraints of neural circuits. This thesis focuses on understanding the theoretical principles governing how neural systems, at various scales, are adapted to the structure of their environment in order to interact with it and perform informa- tion processing tasks efficiently. Here, we study this question in three very different and challenging scenarios: i) how a sensory neural circuit the olfactory pathway is organised to efficiently process odour stimuli in a very high-dimensional space with complex structure; ii) how individual neurons in the sensory periphery exploit the structure in a fast-changing environment to utilise their dynamic range efficiently; iii) how the auditory system of whole organisms is able to efficiently exploit temporal structure in a noisy, fast-changing environment to optimise perception of ambiguous sounds. We also study the theoretical issues in developing principled measures of model complexity and extending classical complexity notions to explicitly account for the scale/resolution at which we observe a system

Analysis of coding principles in the olfactory system and their application in cheminformatics

Unser Geruchssinn vermittelt uns die Wahrnehmung der chemischen Welt. Im Laufe der Evolution haben sich in unserem olfaktorischen System Mechanismen entwickelt, die wahrscheinlich optimal auf die Erfüllung dieser Aufgabe angepasst sind. Die Analyse dieser Verarbeitungsstrategien verspricht Einblicke in effiziente Algorithmen für die Kodierung und Verarbeitung chemischer Information, deren Entwicklung und Anwendung dem Kern der Chemieinformatik entspricht. In dieser Arbeit nähern wir uns der Entschlüsselung dieser Mechanismen durch die rechnerische Modellierung von funktionellen Einheiten des olfaktorischen Systems. Hierbei verfolgten wir einen interdisziplinären Ansatz, der die Gebiete der Chemie, der Neurobiologie und des maschinellen Lernens mit einbezieht

Uncertainty in olfactory decision-making

Relationships between accuracy and speed of decision-making, or speed-accuracy tradeoffs (SAT), have been extensively studied. However, the range of SAT observed varies widely across studies for reasons that are unclear. Several explanations have been proposed, including motivation or incentive for speed vs. accuracy, species and modality but none of these hypotheses has been directly tested. An alternative explanation is that the different degrees of SAT are related to the nature of the task being performed. Here, we addressed this problem by comparing SAT in two odor-guided decision tasks that were identical except for the nature of the task uncertainty: an odor mixture categorization task, where the distinguishing information is reduced by making the stimuli more similar to each other; and an odor identification task in which the information is reduced by lowering the intensity over a range of three log steps. (...

Dynamical structure in neural population activity

The question of how the collective activity of neural populations in the brain gives rise to complex behaviour is fundamental to neuroscience. At the core of this question lie considerations about how neural circuits can perform computations that enable sensory perception, motor control, and decision making. It is thought that such computations are implemented by the dynamical evolution of distributed activity in recurrent circuits. Thus, identifying and interpreting dynamical structure in neural population activity is a key challenge towards a better understanding of neural computation. In this thesis, I make several contributions in addressing this challenge. First, I develop two novel methods for neural data analysis. Both methods aim to extract trajectories of low-dimensional computational state variables directly from the unbinned spike-times of simultaneously recorded neurons on single trials. The first method separates inter-trial variability in the low-dimensional trajectory from variability in the timing of progression along its path, and thus offers a quantification of inter-trial variability in the underlying computational process. The second method simultaneously learns a low-dimensional portrait of the underlying nonlinear dynamics of the circuit, as well as the system's fixed points and locally linearised dynamics around them. This approach facilitates extracting interpretable low-dimensional hypotheses about computation directly from data. Second, I turn to the question of how low-dimensional dynamical structure may be embedded within a high-dimensional neurobiological circuit with excitatory and inhibitory cell-types. I analyse how such circuit-level features shape population activity, with particular focus on responses to targeted optogenetic perturbations of the circuit. Third, I consider the problem of implementing multiple computations in a single dynamical system. I address this in the framework of multi-task learning in recurrently connected networks and demonstrate that a careful organisation of low-dimensional, activity-defined subspaces within the network can help to avoid interference across tasks

Optimal anticipatory control as a theory of motor preparation

Supported by a decade of primate electrophysiological experiments, the prevailing theory of neural motor control holds that movement generation is accomplished by a preparatory process that progressively steers the state of the motor cortex into a movement-specific optimal subspace prior to movement onset. The state of the cortex then evolves from these optimal subspaces, producing patterns of neural activity that serve as control inputs to the musculature. This theory, however, does not address the following questions: what characterizes the optimal subspace and what are the neural mechanisms that underlie the preparatory process? We address these questions with a circuit model of movement preparation and control. Specifically, we propose that preparation can be achieved by optimal feedback control (OFC) of the cortical state via a thalamo-cortical loop. Under OFC, the state of the cortex is selectively controlled along state-space directions that have future motor consequences, and not in other inconsequential ones. We show that OFC enables fast movement preparation and explains the observed orthogonality between preparatory and movement-related monkey motor cortex activity. This illustrates the importance of constraining new theories of neural function with experimental data. However, as recording technologies continue to improve, a key challenge is to extract meaningful insights from increasingly large-scale neural recordings. Latent variable models (LVMs) are powerful tools for addressing this challenge due to their ability to identify the low-dimensional latent variables that best explain these large data sets. One shortcoming of most LVMs, however, is that they assume a Euclidean latent space, while many kinematic variables, such as head rotations and the configuration of an arm, are naturally described by variables that live on non-Euclidean latent spaces (e.g., SO(3) and tori). To address this shortcoming, we propose the Manifold Gaussian Process Latent Variable Model, a method for simultaneously inferring nonparametric tuning curves and latent variables on non-Euclidean latent spaces. We show that our method is able to correctly infer the latent ring topology of the fly and mouse head direction circuits.This work was supported by a Trinity-Henry Barlow scholarship and a scholarship from the Ministry of Education, ROC Taiwan

Modulatory Effects of Acetylcholine and Dopamine on Evoked Synaptic Responses in the Entorhinal Cortex.

The entorhinal cortex connects neocortical areas with the hippocampal formation and other parahippocamal brain areas, and also receives cholinergic projections from the medial septum and dopaminergic projections from the ventral tegmental area. Dopamine and acetylcholine both may contribute to the processing of sensory information in the entorhinal cortex and in other areas of the brain. In Chapter 1, the application of the cholinergic agonist carbachol to entorhinal cortex slices suppressed synaptic transmission in vitro, and experiments determined that the effect was due primarily to activation of M1 muscarinic receptors. Activation of cholinergic receptors also causes a relative facilitation of later responses during theta- and gamma-frequency trains, and because dopamine may modulate gamma and theta oscillations in the entorhinal cortex, Chapter 2 investigated the effect of amphetamine on the amplitudes of synaptic responses during trains of gamma- and theta-frequency stimulation in awake animals. A subset of animals that showed a facilitation of the response to the first pulse of theta-frequency trains due to amphetamine also expressed a synaptic suppression during mobility compared with immobility that was likely due to cholinergic receptor activation. These animals also showed a relative suppression of subsequent responses that was blocked by the D1 receptor antagonist SCH23390 and the D2 receptor antagonist eticlopride. Because previous work in our lab has shown bidirectional effects of differing concentrations of dopamine, Chapter 3 investigated the role of both 10 and 50 μM dopamine in the entorhinal cortex during gamma- and theta-frequency stimulation in vitro. Ten μM dopamine facilitated responses during trains of both frequencies. In contrast, 50 μM dopamine induced a D2 receptor-dependent suppression the first responses and induced a relative facilitation of later responses during the trains, an effect that was only significant for gamma-frequency trains. In general, then, low concentrations of dopamine may enhance repetitive synaptic transmission, while higher concentrations of dopamine may suppress repetitive synaptic transmission within the entorhinal cortex. Because dopamine may modulate learning- related synaptic strengthening, Chapter 4 investigated the effect of 10 μM dopamine on induction of long-term synaptic potentiation (LTP) in entorhinal cortex slices; although dopamine facilitated synaptic responses, it blocked the induction of LTP, suggesting that it may impede learning-related synaptic plasticity. Overall, results indicate that both dopamine and acetylcholine have strong modulatory influences on processes that may affect synaptic integration and plasticity within the entorhinal cortex