Synaptic consolidation: from synapses to behavioral modeling

Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for consolidation and memory retention. We developed a three-layered model of synaptic consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats

The Casimir Force in Randall Sundrum Models

We discuss and compare the effects of one extra dimension in the Randall Sundrum models on the evaluation of the Casimir force between two parallel plates. We impose the condition that the result reproduce the experimental measurements within the known uncertainties in the force and the plate separation, and get an upper bound kR < 20 if the curvature parameter k of AdS_5 is equal to the Planck scale. Although the upper bound decreases as k decreases, kR ~ 12, which is the required value for solving the hierarchy problem, is consistent with the Casimir force measurements. For the case where the 5th dimension is infinite, the correction to the Casimir force is very small and negligible.Comment: 16 pages, 2 figures, references added, text improved, accepted for publication in PR

Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression

Changes in synaptic efficacies need to be long-lasting in order to serve as a substrate for memory. Experimentally, synaptic plasticity exhibits phases covering the induction of long-term potentiation and depression (LTP/LTD) during the early phase of synaptic plasticity, the setting of synaptic tags, a trigger process for protein synthesis, and a slow transition leading to synaptic consolidation during the late phase of synaptic plasticity. We present a mathematical model that describes these different phases of synaptic plasticity. The model explains a large body of experimental data on synaptic tagging and capture, cross-tagging, and the late phases of LTP and LTD. Moreover, the model accounts for the dependence of LTP and LTD induction on voltage and presynaptic stimulation frequency. The stabilization of potentiated synapses during the transition from early to late LTP occurs by protein synthesis dynamics that are shared by groups of synapses. The functional consequence of this shared process is that previously stabilized patterns of strong or weak synapses onto the same postsynaptic neuron are well protected against later changes induced by LTP/LTD protocols at individual synapses

Synaptic consolidation across multiple timescales

The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP), unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC) provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP), require the capture of plasticity-related proteins (PRP). We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the transition from e-LTP to l-LTP. Interestingly, experimental work has linked the production of PRP and the maintenance of memory to the presence of neuromodulators such as dopamine, that can be caused by behavioral and environmental cues such as novelty, reward prediction error, aversive events or attention. We also show that our model of synaptic plasticity and consolidation when simulated and implemented in a network of thousands of model neurons can account for in vivo behavioral data that links memory maintenance to novelty. This supports the hypothesis that behavioral tagging and synaptic tagging could be based on the same mechanistic process