29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

Locomotor patterns and persistent activity in self-organizing neural models

The thesis investigates principles of self-organization that may account for the observed structure and behaviour of neural networks that generate locomotor behaviour and complex spatiotemporal patterns such as spiral waves, metastable states and persistent activity. This relates to the general neuroscience problem of finding the correspondence between the structure of neural networks and their function. This question is both extremely important and difficult to answer because the structure of a neural network defines a specific type of neural dynamics which underpins some function of the neural system and also influences the structure and parameters of the network including connection strengths. This loop of influences results in a stable and reliable neural dynamics that realises a neural function. In order to study the relationship between neural network structure and spatiotemporal dynamics, several computational models of plastic neural networks with different architectures are developed. Plasticity includes both modification of synaptic connection strengths and adaptation of neuronal thresholds. This approach is based on a consideration of general modelling concepts and focuses on a relatively simple neural network which is still complex enough to generate a broad spectrum of spatio-temporal patterns of neural activity such as spiral waves, persistent activity, metastability and phase transitions. Having considered the dynamics of networks with fixed architectures, we go on to consider the question of how a neural circuit which realizes some particular function establishes its architecture of connections. The approach adopted here is to model the developmental process which results in a particular neural network structure which is relevant to some particular functionality; specifically we develop a biologically realistic model of the tadpole spinal cord. This model describes the self-organized process through which the anatomical structure of the full spinal cord of the tadpole develops. Electrophysiological modelling shows that this architecture can generate electrical activity corresponding to the experimentally observed swimming behaviour

Oscillatory architecture of memory circuits

The coordinated activity between remote brain regions underlies cognition and memory function. Although neuronal oscillations have been proposed as a mechanistic substrate for the coordination of information transfer and memory consolidation during sleep, little is known about the mechanisms that support the widespread synchronization of brain regions and the relationship of neuronal dynamics with other bodily rhythms, such as breathing. During exploratory behavior, the hippocampus and the prefrontal cortex are organized by theta oscillations, known to support memory encoding and retrieval, while during sleep the same structures are dominated by slow oscillations that are believed to underlie the consolidation of recent experiences. The expression of conditioned fear and extinction memories relies on the coordinated activity between the mPFC and the basolateral amygdala (BLA), a neuronal structure encoding associative fear memories. However, to date, the mechanisms allowing this long-range network synchronization of neuronal activity between the mPFC and BLA during fear behavior remain virtually unknown. Using a combination of extracellular recordings and open- and closed-loop optogenetic manipulations, we investigated the oscillatory and coding mechanisms mediating the organization and coupling of the limbic circuit in the awake and asleep brain, as well as during memory encoding and retrieval. We found that freezing, a behavioral expression of fear, is tightly associated with an internally generated brain state that manifests in sustained 4Hz oscillatory dynamics in prefrontal-amygdala circuits. 4Hz oscillations accurately predict the onset and termination of the freezing state. These oscillations synchronize prefrontal-amygdala circuits and entrain neuronal activity to dynamically regulate the development of neuronal ensembles. This enables the precise timing of information transfer between the two structures and the expression of fear responses. Optogenetic induction of prefrontal 4Hz oscillations promotes freezing behavior and the formation of long-lasting fear memory, while closed-loop phase specific manipulations bidirectionally modulate fear expression. Our results unravel a physiological signature of fear memory and identify a novel internally generated brain state, characterized by 4Hz oscillations. This oscillation enables the temporal coordination and information transfer in the prefrontal-amygdala circuit via a phase-specific coding mechanism, facilitating the encoding and expression of fear memory. In the search for the origin of this oscillation, we focused our attention on breathing, the most fundamental and ubiquitous rhythmic activity in life. Using large-scale extracellular recordings from a number of structures, including the medial prefrontal cortex, hippocampus, thalamus, amygdala and nucleus accumbens in mice we identified and characterized the entrainment by breathing of a host of network dynamics across the limbic circuit. We established that fear-related 4Hz oscillations are a state-specific manifestation of this cortical entrainment by the respiratory rhythm. We characterized the translaminar and transregional profile of this entrainment and demonstrated a causal role of breathing in synchronizing neuronal activity and network dynamics between these structures in a variety of behavioral scenarios in the awake and sleep state. We further revealed a dual mechanism of respiratory entrainment, in the form of an intracerebral corollary discharge that acts jointly with an olfactory reafference to coordinate limbic network dynamics, such as hippocampal ripples and cortical UP and DOWN states, involved in memory consolidation. Respiration provides a perennial stream of rhythmic input to the brain. In addition to its role as the condicio sine qua non for life, here we provide evidence that breathing rhythm acts as a global pacemaker for the brain, providing a reference signal that enables the integration of exteroceptive and interoceptive inputs with the internally generated dynamics of the hippocampus and the neocortex. Our results highlight breathing, a perennial rhythmic input to the brain, as an oscillatory scaffold for the functional coordination of the limbic circuit, enabling the segregation and integration of information flow across neuronal networks

Learning and Decision Making in Social Contexts: Neural and Computational Models

Social interaction is one of humanity's defining features. Through it, we develop ideas, express emotions, and form relationships. In this thesis, we explore the topic of social cognition by building biologically-plausible computational models of learning and decision making. Our goal is to develop mechanistic explanations for how the brain performs a variety of social tasks, to test those theories by simulating neural networks, and to validate our models by comparing to human and animal data. We begin by introducing social cognition from functional and anatomical perspectives, then present the Neural Engineering Framework, which we use throughout the thesis to specify functional brain models. Over the course of four chapters, we investigate many aspects of social cognition using these models. We begin by studying fear conditioning using an anatomically accurate model of the amygdala. We validate this model by comparing the response properties of our simulated neurons with real amygdala neurons, showing that simulated behavior is consistent with animal data, and exploring how simulated fear generalization relates to normal and anxious humans. Next, we show that biologically-detailed networks may realize cognitive operations that are essential for social cognition. We validate this approach by constructing a working memory network from multi-compartment cells and conductance-based synapses, then show that its mnemonic performance is comparable to animals performing a delayed match-to-sample task. In the next chapter, we study decision making and the tradeoffs between speed and accuracy: our network gathers information from the environment and tracks the value of choice alternatives, making a decision once certain criteria are met. We apply this model to a two-choice decision task, fit model parameters to recreate the behavior of individual humans, and reproduce the speed-accuracy tradeoff evident in the human population. Finally, we combine our networks for learning, working memory, and decision making into a cognitive agent that uses reinforcement learning to play a simple social game. We compare this model with two other cognitive architectures and with human data from an experiment we ran, and show that our three cognitive agents recreate important patterns in the human data, especially those related to social value orientation and cooperative behavior. Our concluding chapter summarizes our contributions to the field of social cognition and proposes directions for further research. The main contribution of this thesis is the demonstration that a diverse set of social cognitive abilities may be explained, simulated, and validated using a functionally-descriptive, biologically-plausible theoretical framework. Our models lay a foundation for studying increasingly-sophisticated forms of social cognition in future work