Biomedical subjects

Harel Z Shouval

Publications and source records attributed to Harel Z Shouval.

10 recordsLinked to original sources

PubMed2006

Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in visual cortex and hippocampus.

Various forms of synaptic plasticity, including spike timing-dependent plasticity, can be accounted for by calcium-dependent models of synaptic plasticity. However, recent results in which synaptic plasticity is induced by multi-spike protocols cannot simply be accounted for by linear superposition of plasticity due to spike pairs or by existing calcium-dependent models. In this paper, we show that multi-spike protocols can be accounted for if, in addition to the dynamics of back-propagating action potentials, stochastic synaptic dynamics are taken into account. We show that a stochastic implementation can account for the data better than a deterministic implementation and is also more robust. Our results demonstrate that differences between experimental results obtained in hippocampus and visual cortex can be accounted for by the different synaptic and dendritic dynamics in these two systems.

Action Potentials↗

PubMed2006

A biophysical basis for the inter-spike interaction of spike-timing-dependent plasticity.

Although spike-timing-dependent plasticity (STDP) is well characterized when pre- and postsynaptic spikes are paired with a given time lag, how this generalizes for more complex spike-trains is unclear. Recent experiments demonstrate that contributions to synaptic plasticity from different spike pairs within a spike train do not add linearly. In the visual cortex conditioning with spike triplets shows that the effect of the first spike pair dominates over the second. Using a previously proposed calcium-dependent plasticity model, we show that short-term synaptic dynamics and interaction between successive back-propagating action potentials (BPAP) may jointly account for the nonlinearities observed. Paired-pulse depression and attenuation of BPAPs are incorporated into the model through the use-dependent depletion of pre- and postsynaptic resources, respectively. Simulations suggest that these processes may play critical roles in determining how STDP operates in the context of natural spike-trains.

Action Potentials↗

PubMed2006

Stimulus for rapid ocular dominance plasticity in visual cortex.

Although it has been known for decades that monocular deprivation shifts ocular dominance in kitten striate cortex, uncertainty persists about the adequate stimulus for deprivation-induced losses of cortical responsiveness. In the current study we compared the effects of 2 days of lid closure and 2 days of monocular blur using an overcorrecting contact lens. Our finding of comparable ocular dominance shifts in visual cortex indicates that deprived-eye response depression is not a result of reduced retinal illumination. The quality rather than the quantity of retinal illumination is the key factor for ocular dominance plasticity. These data have implications for both the mechanism and treatment of amblyopia.

Action Potentials↗

PubMed2005

Clusters of interacting receptors can stabilize synaptic efficacies.

Synaptic weights store memories that can last a lifetime. Yet, memory depends on synaptic protein receptors that are recycled in and out of the membrane at a fast rate, possibly several times an hour. Several proposals to bridge this vast gap in time scales between memory and its molecular substrate have relied on bistable molecular switches. Here, we propose an alternative to this approach based on clusters of interacting receptors in the synaptic membrane. We show that such clusters can be metastable and that the lifetime of such clusters can be many orders of magnitude larger than the lifetime of the receptors of which they are composed. We also demonstrate how bidirectional synaptic plasticity can be implemented in this framework.

Computer Simulation↗

PubMed2005

A model of bidirectional synaptic plasticity: from signaling network to channel conductance.

In many regions of the brain, including the mammalian cortex, the strength of synaptic transmission can be bidirectionally regulated by cortical activity (synaptic plasticity). One line of evidence indicates that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD), correlate with the phosphorylation/dephosphorylation of sites on the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit protein GluR1. Bidirectional synaptic plasticity can be induced by different frequencies of presynaptic stimulation, but there is considerable evidence indicating that the key variable is calcium influx through postsynaptic N-methyl-d-aspartate (NMDA) receptors. Here, we present a biophysical model of bidirectional synaptic plasticity based on [Ca2+]-dependent phospho/dephosphorylation of the GluR1 subunit of the AMPA receptor. The primary assumption of the model, for which there is wide experimental support, is that the postsynaptic calcium concentration, and consequent activation of calcium-dependent protein kinases and phosphatases, is the trigger for phosphorylation/dephosphorylation at GluR1 and consequent induction of LTP/LTD. We explore several different mathematical approaches, all of them based on mass-action assumptions. First, we use a first order approach, in which transition rates are functions of an activator, in this case calcium. Second, we adopt the Michaelis-Menten approach with different assumptions about the signal transduction cascades, ranging from abstract to more detailed and biologically plausible models. Despite the different assumptions made in each model, in each case, LTD is induced by a moderate increase in postsynaptic calcium and LTP is induced by high Ca2+ concentration.

Animals↗

PubMed2004

Synaptic homeostasis and input selectivity follow from a calcium-dependent plasticity model.

Modifications in the strengths of synapses are thought to underlie memory, learning, and development of cortical circuits. Many cellular mechanisms of synaptic plasticity have been investigated in which differential elevations of postsynaptic calcium concentrations play a key role in determining the direction and magnitude of synaptic changes. We have previously described a model of plasticity that uses calcium currents mediated by N-methyl-D-aspartate receptors as the associative signal for Hebbian learning. However, this model is not completely stable. Here, we propose a mechanism of stabilization through homeostatic regulation of intracellular calcium levels. With this model, synapses are stable and exhibit properties such as those observed in metaplasticity and synaptic scaling. In addition, the model displays synaptic competition, allowing structures to emerge in the synaptic space that reflect the statistical properties of the inputs. Therefore, the combination of a fast calcium-dependent learning and a slow stabilization mechanism can account for both the formation of selective receptive fields and the maintenance of neural circuits in a state of equilibrium.

Animals↗

PubMed2004

Stochastic properties of synaptic transmission affect the shape of spike time-dependent plasticity curves.

Theoretical studies have shown that calcium influx through N-methyl-D-aspartate (NMDA) receptors is a sufficient signal to account for various induction protocols of bidirectional synaptic plasticity, including spike time-dependent plasticity (STDP). The STDP curves obtained by these different models exhibits a form of spike time-dependent long-term depression that occurs when a presynaptic spike precedes the postsynaptic spike (pre-post LTD). We have previously proposed that this novel form of LTD can serve as an experimental test for the validity of these models. These calcium based theoretical models assumed deterministic calcium dynamics that reflect average properties of synaptic calcium currents. In this paper, we show that taking into account the stochastic properties of synaptic transmission significantly alters the form of STDP curves and may significantly reduce the magnitude of pre-post LTD.

Action Potentials↗

PubMed2004

Analysis of the intraspinal calcium dynamics and its implications for the plasticity of spiking neurons.

The influx of calcium ions into the dendritic spines through the N-methyl-D-aspartate (NMDA) channels is believed to be the primary trigger for various forms of synaptic plasticity. In this paper, the authors calculate analytically the mean values of the calcium transients elicited by a spiking neuron undergoing a simple model of ionic currents and back-propagating action potentials. The relative variability of these transients, due to the stochastic nature of synaptic transmission, is further considered using a simple Markov model of NMDA receptors. One finds that both the mean value and the variability depend on the timing between presynaptic and postsynaptic action potentials. These results could have implications for the expected form of the synaptic-plasticity curve and can form a basis for a unified theory of spike-time-dependent, and rate-based plasticity.

Action Potentials↗

PubMed2002

A unified model of NMDA receptor-dependent bidirectional synaptic plasticity.

Synapses in the brain are bidirectionally modifiable, but the routes of induction are diverse. In various experimental paradigms, N-methyl-d-aspartate receptor-dependent long-term depression and long-term potentiation have been induced selectively by varying the membrane potential of the postsynaptic neurons during presynaptic stimulation of a constant frequency, the rate of presynaptic stimulation, and the timing of pre- and postsynaptic action potentials. In this paper, we present a mathematical embodiment of bidirectional synaptic plasticity that is able to explain diverse induction protocols with a fixed set of parameters. The key assumptions and consequences of the model can be tested experimentally; further, the model provides the foundation for a unified theory of N-methyl-d-aspartate receptor-dependent synaptic plasticity.

Action Potentials↗

PubMed2002

Converging evidence for a simplified biophysical model of synaptic plasticity.

Different mechanisms that could form the molecular basis for bi-directional synaptic plasticity have been identified experimentally and corresponding biophysical models can be constructed. However, such models are complex and therefore it is hard to deduce their consequences to compare them to existing abstract models of synaptic plasticity. In this paper we examine two such models: a phenomenological one inspired by the phenomena of AMPA receptor insertion, and a more complex biophysical model based on the phenomena of AMPA receptor phosphorylation. We show that under certain approximations both these models can be mapped on to an equivalent, calcium-dependent, differential equation. Intracellular calcium concentration varies locally in each postsynaptic compartment, thus the plasticity rule we extract is a single-synapse rule. We convert this single synapse plasticity equation to a multi-synapse rule by incorporating a model of the NMDA receptor. Finally we suggest a mathematical embodiment of metaplasticity, which is consistent with observations on NMDA receptor properties and dependence on cellular activity. These results, in combination with some of our previous results, produce converging evidence for the calcium control hypothesis including a dependence of synaptic plasticity on the level of intercellular calcium as well as on the temporal pattern of calcium transients.

Animals↗