868 research outputs found
Reconstructing the three-dimensional GABAergic microcircuit of the striatum
A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study
Stochastic Continuous Time Neurite Branching Models with Tree and Segment Dependent Rates
In this paper we introduce a continuous time stochastic neurite branching
model closely related to the discrete time stochastic BES-model. The discrete
time BES-model is underlying current attempts to simulate cortical development,
but is difficult to analyze. The new continuous time formulation facilitates
analytical treatment thus allowing us to examine the structure of the model
more closely. We derive explicit expressions for the time dependent
probabilities p(\gamma, t) for finding a tree \gamma at time t, valid for
arbitrary continuous time branching models with tree and segment dependent
branching rates. We show, for the specific case of the continuous time
BES-model, that as expected from our model formulation, the sums needed to
evaluate expectation values of functions of the terminal segment number
\mu(f(n),t) do not depend on the distribution of the total branching
probability over the terminal segments. In addition, we derive a system of
differential equations for the probabilities p(n,t) of finding n terminal
segments at time t. For the continuous BES-model, this system of differential
equations gives direct numerical access to functions only depending on the
number of terminal segments, and we use this to evaluate the development of the
mean and standard deviation of the number of terminal segments at a time t. For
comparison we discuss two cases where mean and variance of the number of
terminal segments are exactly solvable. Then we discuss the numerical
evaluation of the S-dependence of the solutions for the continuous time
BES-model. The numerical results show clearly that higher S values, i.e. values
such that more proximal terminal segments have higher branching rates than more
distal terminal segments, lead to more symmetrical trees as measured by three
tree symmetry indicators.Comment: 41 pages, 2 figures, revised structure and text improvement
Recommended from our members
An Optimized Structure-Function Design Principle Underlies Efficient Signaling Dynamics in Neurons.
Dynamic signaling on branching axons is critical for rapid and efficient communication between neurons in the brain. Efficient signaling in axon arbors depends on a trade-off between the time it takes action potentials to reach synaptic terminals (temporal cost) and the amount of cellular material associated with the wiring path length of the neuron's morphology (material cost). However, where the balance between structural and dynamical considerations for achieving signaling efficiency is, and the design principle that neurons optimize to preserve this balance, is still elusive. In this work, we introduce a novel analysis that compares morphology and signaling dynamics in axonal networks to address this open problem. We show that in Basket cell neurons the design principle being optimized is the ratio between the refractory period of the membrane, and action potential latencies between the initial segment and the synaptic terminals. Our results suggest that the convoluted paths taken by axons reflect a design compensation by the neuron to slow down signaling latencies in order to optimize this ratio. Deviations in this ratio may result in a breakdown of signaling efficiency in the cell. These results pave the way to new approaches for investigating more complex neurophysiological phenomena that involve considerations of neuronal structure-function relationships
Simulation of networks of spiking neurons: A review of tools and strategies
We review different aspects of the simulation of spiking neural networks. We
start by reviewing the different types of simulation strategies and algorithms
that are currently implemented. We next review the precision of those
simulation strategies, in particular in cases where plasticity depends on the
exact timing of the spikes. We overview different simulators and simulation
environments presently available (restricted to those freely available, open
source and documented). For each simulation tool, its advantages and pitfalls
are reviewed, with an aim to allow the reader to identify which simulator is
appropriate for a given task. Finally, we provide a series of benchmark
simulations of different types of networks of spiking neurons, including
Hodgkin-Huxley type, integrate-and-fire models, interacting with current-based
or conductance-based synapses, using clock-driven or event-driven integration
strategies. The same set of models are implemented on the different simulators,
and the codes are made available. The ultimate goal of this review is to
provide a resource to facilitate identifying the appropriate integration
strategy and simulation tool to use for a given modeling problem related to
spiking neural networks.Comment: 49 pages, 24 figures, 1 table; review article, Journal of
Computational Neuroscience, in press (2007
Design for a Darwinian Brain: Part 1. Philosophy and Neuroscience
Physical symbol systems are needed for open-ended cognition. A good way to
understand physical symbol systems is by comparison of thought to chemistry.
Both have systematicity, productivity and compositionality. The state of the
art in cognitive architectures for open-ended cognition is critically assessed.
I conclude that a cognitive architecture that evolves symbol structures in the
brain is a promising candidate to explain open-ended cognition. Part 2 of the
paper presents such a cognitive architecture.Comment: Darwinian Neurodynamics. Submitted as a two part paper to Living
Machines 2013 Natural History Museum, Londo
An axon initial segment is required for temporal precision in action potential encoding by neuronal populations
Central neurons initiate action potentials (APs) in the axon initial segment
(AIS), a compartment characterized by a high concentration of voltage-dependent
ion channels and specialized cytoskeletal anchoring proteins arranged in a
regular nanoscale pattern. Although the AIS was a key evolutionary innovation
in neurons, the functional benefits it confers are not clear. Using a mutation
of the AIS cytoskeletal protein \beta IV-spectrin, we here establish an in
vitro model of neurons with a perturbed AIS architecture that retains nanoscale
order but loses the ability to maintain a high NaV density. Combining
experiments and simulations we show that a high NaV density in the AIS is not
required for axonal AP initiation; it is however crucial for a high bandwidth
of information encoding and AP timing precision. Our results provide the first
experimental demonstration of axonal AP initiation without high axonal channel
density and suggest that increasing the bandwidth of the neuronal code and
hence the computational efficiency of network function was a major benefit of
the evolution of the AIS.Comment: Title adjusted, no other change
Stochastic generation of biologically accurate brain networks
Basic circuits, which form the building blocks of the brain, have been identiffied
in recent literature. We propose to treat these basic circuits as "stochastic generators"
whose instances serve to wire a portion of the mouse brain. Very much in the same
manner as genes generate proteins by providing templates for their construction, we
view the catalog of basic circuits as providing templates for wiring up the neurons
of the brain. This thesis work involves a) deffining a framework for the stochastic
generation of brain networks, b) generation of sample networks from the basic circuits,
and c) visualization of the generated networks
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
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