Modeling Maintenance of Long-Term Potentiation in Clustered Synapses, Long-Term Memory Without Bistability

Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Bistability of single synapses has also never been empirically demonstrated. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (in excess of 1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the clustered plasticity hypothesis, which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions, and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.Comment: 17 pages, 5 figure

Linear stability in networks of pulse-coupled neurons

In a first step towards the comprehension of neural activity, one should focus on the stability of the various dynamical states. Even the characterization of idealized regimes, such as a perfectly periodic spiking activity, reveals unexpected difficulties. In this paper we discuss a general approach to linear stability of pulse-coupled neural networks for generic phase-response curves and post-synaptic response functions. In particular, we present: (i) a mean-field approach developed under the hypothesis of an infinite network and small synaptic conductances; (ii) a "microscopic" approach which applies to finite but large networks. As a result, we find that no matter how large is a neural network, its response to most of the perturbations depends on the system size. There exists, however, also a second class of perturbations, whose evolution typically covers an increasingly wide range of time scales. The analysis of perfectly regular, asynchronous, states reveals that their stability depends crucially on the smoothness of both the phase-response curve and the transmitted post-synaptic pulse. The general validity of this scenarion is confirmed by numerical simulations of systems that are not amenable to a perturbative approach.Comment: 13 pages, 7 figures, submitted to Frontiers in Computational Neuroscienc

Adaptation controls synchrony and cluster states of coupled threshold-model neurons

We analyze zero-lag and cluster synchrony of delay-coupled non-smooth dynamical systems by extending the master stability approach, and apply this to networks of adaptive threshold-model neurons. For a homogeneous population of excitatory and inhibitory neurons we find (i) that subthreshold adaptation stabilizes or destabilizes synchrony depending on whether the recurrent synaptic excitatory or inhibitory couplings dominate, and (ii) that synchrony is always unstable for networks with balanced recurrent synaptic inputs. If couplings are not too strong, synchronization properties are similar for very different coupling topologies, i.e., random connections or spatial networks with localized connectivity. We generalize our approach for two subpopulations of neurons with non-identical local dynamics, including bursting, for which activity-based adaptation controls the stability of cluster states, independent of a specific coupling topology.Comment: 11 pages, 5 figure

Instability of frozen-in states in synchronous Hebbian neural networks

The full dynamics of a synchronous recurrent neural network model with Ising binary units and a Hebbian learning rule with a finite self-interaction is studied in order to determine the stability to synaptic and stochastic noise of frozen-in states that appear in the absence of both kinds of noise. Both, the numerical simulation procedure of Eissfeller and Opper and a new alternative procedure that allows to follow the dynamics over larger time scales have been used in this work. It is shown that synaptic noise destabilizes the frozen-in states and yields either retrieval or paramagnetic states for not too large stochastic noise. The indications are that the same results may follow in the absence of synaptic noise, for low stochastic noise.Comment: 14 pages and 4 figures; accepted for publication in J. Phys. A: Math. Ge

Mean Field Analysis of Stochastic Neural Network Models with Synaptic Depression

We investigated the effects of synaptic depression on the macroscopic behavior of stochastic neural networks. Dynamical mean field equations were derived for such networks by taking the average of two stochastic variables: a firing state variable and a synaptic variable. In these equations, their average product is decoupled as the product of averaged them because the two stochastic variables are independent. We proved the independence of these two stochastic variables assuming that the synaptic weight is of the order of 1/N with respect to the number of neurons N. Using these equations, we derived macroscopic steady state equations for a network with uniform connections and a ring attractor network with Mexican hat type connectivity and investigated the stability of the steady state solutions. An oscillatory uniform state was observed in the network with uniform connections due to a Hopf instability. With the ring network, high-frequency perturbations were shown not to affect system stability. Two mechanisms destabilize the inhomogeneous steady state, leading two oscillatory states. A Turing instability leads to a rotating bump state, while a Hopf instability leads to an oscillatory bump state, which was previous unreported. Various oscillatory states take place in a network with synaptic depression depending on the strength of the interneuron connections.Comment: 26 pages, 13 figures. Preliminary results for the present work have been published elsewhere (Y Igarashi et al., 2009. http://www.iop.org/EJ/abstract/1742-6596/197/1/012018

Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer's disease.

The abundance of mRNA is mainly determined by the rates of RNA transcription and decay. Here, we present a method for unbiased estimation of differential mRNA decay rate from RNA-sequencing data by modeling the kinetics of mRNA metabolism. We show that in all primary human tissues tested, and particularly in the central nervous system, many pathways are regulated at the mRNA stability level. We present a parsimonious regulatory model consisting of two RNA-binding proteins and four microRNAs that modulate the mRNA stability landscape of the brain, which suggests a new link between RBFOX proteins and Alzheimer's disease. We show that downregulation of RBFOX1 leads to destabilization of mRNAs encoding for synaptic transmission proteins, which may contribute to the loss of synaptic function in Alzheimer's disease. RBFOX1 downregulation is more likely to occur in older and female individuals, consistent with the association of Alzheimer's disease with age and gender."mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer's disease.