Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

The striatum, the principal input structure of the basal ganglia, is crucial to both motor control and learning. It receives convergent input from all over the neocortex, hippocampal formation, amygdala and thalamus, and is the primary recipient of dopamine in the brain. Within the striatum is a GABAergic microcircuit that acts upon these inputs, formed by the dominant medium-spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs). There has been little progress in understanding the computations it performs, hampered by the non-laminar structure that prevents identification of a repeating canonical microcircuit. We here begin the identification of potential dynamically-defined computational elements within the striatum. We construct a new three-dimensional model of the striatal microcircuit's connectivity, and instantiate this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs is introduced and tuned to experimental data. We introduce a novel multiple spike-train analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time-scales. We find that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appear, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation is strongly dependent on the simulated concentration of dopamine. We also show that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs. Such small cell assemblies forming spontaneously only in the absence of dopamine may contribute to motor control problems seen in humans and animals following a loss of dopamine cells. (C) 2009 Elsevier Ltd. All rights reserved

Fundamental activity constraints lead to specific interpretations of the connectome

The continuous integration of experimental data into coherent models of the brain is an increasing challenge of modern neuroscience. Such models provide a bridge between structure and activity, and identify the mechanisms giving rise to experimental observations. Nevertheless, structurally realistic network models of spiking neurons are necessarily underconstrained even if experimental data on brain connectivity are incorporated to the best of our knowledge. Guided by physiological observations, any model must therefore explore the parameter ranges within the uncertainty of the data. Based on simulation results alone, however, the mechanisms underlying stable and physiologically realistic activity often remain obscure. We here employ a mean-field reduction of the dynamics, which allows us to include activity constraints into the process of model construction. We shape the phase space of a multi-scale network model of the vision-related areas of macaque cortex by systematically refining its connectivity. Fundamental constraints on the activity, i.e., prohibiting quiescence and requiring global stability, prove sufficient to obtain realistic layer- and area-specific activity. Only small adaptations of the structure are required, showing that the network operates close to an instability. The procedure identifies components of the network critical to its collective dynamics and creates hypotheses for structural data and future experiments. The method can be applied to networks involving any neuron model with a known gain function.Comment: J. Schuecker and M. Schmidt contributed equally to this wor

Neuronal assembly dynamics in supervised and unsupervised learning scenarios

The dynamic formation of groups of neurons—neuronal assemblies—is believed to mediate cognitive phenomena at many levels, but their detailed operation and mechanisms of interaction are still to be uncovered. One hypothesis suggests that synchronized oscillations underpin their formation and functioning, with a focus on the temporal structure of neuronal signals. In this context, we investigate neuronal assembly dynamics in two complementary scenarios: the first, a supervised spike pattern classification task, in which noisy variations of a collection of spikes have to be correctly labeled; the second, an unsupervised, minimally cognitive evolutionary robotics tasks, in which an evolved agent has to cope with multiple, possibly conflicting, objectives. In both cases, the more traditional dynamical analysis of the system’s variables is paired with information-theoretic techniques in order to get a broader picture of the ongoing interactions with and within the network. The neural network model is inspired by the Kuramoto model of coupled phase oscillators and allows one to fine-tune the network synchronization dynamics and assembly configuration. The experiments explore the computational power, redundancy, and generalization capability of neuronal circuits, demonstrating that performance depends nonlinearly on the number of assemblies and neurons in the network and showing that the framework can be exploited to generate minimally cognitive behaviors, with dynamic assembly formation accounting for varying degrees of stimuli modulation of the sensorimotor interactions

Integration of continuous-time dynamics in a spiking neural network simulator

Contemporary modeling approaches to the dynamics of neural networks consider two main classes of models: biologically grounded spiking neurons and functionally inspired rate-based units. The unified simulation framework presented here supports the combination of the two for multi-scale modeling approaches, the quantitative validation of mean-field approaches by spiking network simulations, and an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most efficient spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. We further demonstrate the broad applicability of the framework by considering various examples from the literature ranging from random networks to neural field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Network Plasticity as Bayesian Inference

General results from statistical learning theory suggest to understand not only brain computations, but also brain plasticity as probabilistic inference. But a model for that has been missing. We propose that inherently stochastic features of synaptic plasticity and spine motility enable cortical networks of neurons to carry out probabilistic inference by sampling from a posterior distribution of network configurations. This model provides a viable alternative to existing models that propose convergence of parameters to maximum likelihood values. It explains how priors on weight distributions and connection probabilities can be merged optimally with learned experience, how cortical networks can generalize learned information so well to novel experiences, and how they can compensate continuously for unforeseen disturbances of the network. The resulting new theory of network plasticity explains from a functional perspective a number of experimental data on stochastic aspects of synaptic plasticity that previously appeared to be quite puzzling.Comment: 33 pages, 5 figures, the supplement is available on the author's web page http://www.igi.tugraz.at/kappe

Construction of a multi-scale spiking model of macaque visual cortex

Understanding the relationship between structure and dynamics of the mammalian cortex is a key challenge of neuroscience. So far, it has been tackled in two ways: by modeling neurons or small circuits in great detail, and through large-scale models representing each area with a small number of differential equations. To bridge the gap between these two approaches, we construct a spiking network model extending earlier work on the cortical microcircuit by Potjans & Diesmann (2014) to all 32 areas of the macaque visual cortex in the parcellation of Felleman & Van Essen (1991). The model takes into account spe- cific neuronal densities and laminar thicknesses of the individual areas. The connectivity of the model combines recently updated binary tracing data from the CoCoMac database (Stephan et al., 2001) with quantitative tracing data providing connection densities (Markov et al., 2014a) and laminar connection patterns (Stephan et al., 2001; Markov et al., 2014b). We estimate missing data using structural regular- ities such as the exponential decay of connection densities with distance between areas (Ercsey-Ravasz et al., 2013) and a fit of laminar patterns versus logarithmic ratios of neuron densities. The model integrates a large body of knowledge on the structure of macaque visual cortex into a consistent framework that allows for progressive refinement