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Luboeinski, J.

Publications and source records attributed to Luboeinski, J..

3 recordsLinked to original sources

A biophysical model of synaptic tagging-and-capture based on actin dynamics

According to the synaptic tagging-and-capture hypothesis, long-term synaptic plasticity requires postsynaptic sites to establish a synaptic tag, enabling them to capture plasticity-related products synthesized elsewhere in the neuron. Although electrophysiological studies have provided evidence for the existence of synaptic tags, it remains largely unresolved which biophysical processes or synaptic molecules or properties implement them. In this study, we examine the hypothesis that a mismatch between dendritic spine volume and the size of the postsynaptic density (PSD) inheres the essential characteristics of a synaptic tag. To test this hypothesis, we developed a computational model that integrates established principles of calcium-dependent synaptic plasticity with the complex biochemical dynamics of actin, which is a key structural protein determining dendritic spine geometry. Using this model, we demonstrate the plausibility of our hypothesis by showing that the model can reproduce and explain a broad range of experimental findings across diverse synaptic plasticity protocols at the level of individual synapses as well as heterosynaptic plasticity protocols involving two synapses. Furthermore, the model predicts that the repeated induction of plasticity within a one-hour time window results in a nonlinear accumulation of synaptic changes, reminiscent of the spacing effect observed in psychological studies of learning and memory. These results offer a concise mechanistic framework for understanding critical synaptic processes and suggest how temporal disparities in structural and biochemical dynamics can form a memory trace that could act as a synaptic tag.

neuroscience↗

Organization and priming of long-term memory representations with two-phase plasticity

Synaptic tagging and capture (STC) is a molecular mechanism that accounts for the consolidation of synaptic changes induced by plasticity. To link this mechanism to long-term memory and thereby to the level of behavior, its dynamics on the level of recurrent networks have to be understood. To this end, we employ a biologically detailed neural network model of spiking neurons featuring STC, which models the learning and consolidation of long-term memory representations. Using this model, we investigate the effects of different organizational paradigms of multiple memory representations, and demonstrate a proof of principle for priming on long timescales. We examine these effects considering the spontaneous activation of memory representations as the network is driven by background noise. Our first finding is that the order in which the memory representations are learned significantly biases the likelihood of spontaneous activation towards more recently learned memory representations. Secondly, we find that hub-like structures counter this learning order effect for representations with less overlaps. We show that long-term depression is the mechanism underlying these findings, and that intermediate consolidation in between learning the individual representations strongly alters the described effects. Finally, we employ STC to demonstrate the priming of a long-term memory representation on a timescale of minutes to hours. As shown by these findings, our model provides a mechanistic synaptic and neuronal basis for known behavioral effects.

neuroscience↗

Memory consolidation and improvement by synaptic tagging and capture in recurrent neural networks

The synaptic-tagging-and-capture (STC) hypothesis formulates that at each synapse the concurrence of a tag with protein synthesis yields the maintenance of changes induced by synaptic plasticity. This hypothesis provides a biological principle underlying the synaptic consolidation of memories that is not verified for recurrent neural circuits. We developed a theoretical model integrating the mechanisms underlying the STC hypothesis with calcium-based synaptic plasticity in a recurrent spiking neural network. In the model, calcium-based synaptic plasticity yields the formation of strongly interconnected cell assemblies encoding memories, followed by consolidation through the STC mechanisms. Furthermore, we find that the STC mechanisms have an up to now undiscovered effect on memories - with the passage of time they modify the storage of memories, such that after several hours memory recall is significantly improved. This kind of memory enhancement can provide a new principle for storing information in biological and artificial neural circuits.

neuroscience↗