Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userComparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation
71
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
How can memories be maintained from days to a lifetime, given turnover of proteins that underlie expression of long-term synaptic potentiation (LTP)? One likely solution relies on synaptic positive feedback loops, prominently including persistent activation of CaM kinase II (CaMKII) and self-activated synthesis of protein kinase M zeta (PKM). Recent studies also suggest positive feedback based on recurrent synaptic reactivation within neuron assemblies, or engrams, is necessary to maintain memories. The relative importance of these feedback mechanisms is controversial. To explore the likelihood that each mechanism is necessary or sufficient, we simulated LTP maintenance with a simplified model incorporating persistent kinase activation, synaptic tagging, and preferential reactivation of strong synapses, and analyzed implications of recent data. We simulated three model variants, each maintaining LTP with one feedback loop: self-activated PKM synthesis (variant I); self-activated CamKII (variant II); and recurrent reactivation of strengthened synapses (variant III). Variant I requires and predicts that PKM must contribute to synaptic tagging. Variant II maintains LTP and suggests persistent CaMKII activation could maintain PKM activity, a feedforward interaction not previously considered. However we note data challenging this feedback loop. In variant III synaptic reactivation drives, and thus predicts, recurrent or persistent activity elevations of CamKII and other necessary kinases, plausibly contributing to empirically persistent elevation of PKM levels. Reactivation is thus predicted to sustain recurrent rounds of synaptic tagging and incorporation of plasticity-related proteins. We also suggest (model variant IV) that synaptic reactivation and autonomous kinase activation could synergistically maintain LTP. We propose experiments that could discriminate these maintenance mechanisms.
rate research
Read More
Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of the enzyme protein kinase M (PKM) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been tagged by an stimulus sufficient for LTP and learning can capture PKM. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKM, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKM. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKM enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKM. Second, cross capture requires the induction of LTD to induce dendritic PKM synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKM inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.
We first review traditional approaches to memory storage and formation, drawing on the literature of quantitative neuroscience as well as statistical physics. These have generally focused on the fast dynamics of neurons; however, there is now an increasing emphasis on the slow dynamics of synapses, whose weight changes are held to be responsible for memory storage. An important first step in this direction was taken in the context of Fusis cascade model, where complex synaptic architectures were invoked, in particular, to store long-term memories. No explicit synaptic dynamics were, however, invoked in that work. These were recently incorporated theoretically using the techniques used in agent-based modelling, and subsequently, models of competing and cooperating synapses were formulated. It was found that the key to the storage of long-term memories lay in the competitive dynamics of synapses. In this review, we focus on models of synaptic competition and cooperation, and look at the outstanding challenges that remain.
In continuous attractor neural networks (CANNs), spatially continuous information such as orientation, head direction, and spatial location is represented by Gaussian-like tuning curves that can be displaced continuously in the space of the preferred stimuli of the neurons. We investigate how short-term synaptic depression (STD) can reshape the intrinsic dynamics of the CANN model and its responses to a single static input. In particular, CANNs with STD can support various complex firing patterns and chaotic behaviors. These chaotic behaviors have the potential to encode various stimuli in the neuronal system.
Astrocytes affect neural transmission by a tight control via glutamate transporters on glutamate concentrations in direct vicinity to the synaptic cleft and by extracellular glutamate. Their relevance for information representation has been supported by in-vivo studies in ferret and mouse primary visual cortex. In ferret blocking glutamate transport pharmacologically broadened tuning curves and enhanced the response at preferred orientation. In knock-out mice with reduced expression of glutamate transporters sharpened tuning was observed. It is however unclear how focal and ambient changes in glutamate concentration affect stimulus representation. Here we develop a computational framework, which allows the investigation of synaptic and extrasynaptic effects of glutamate uptake on orientation tuning in recurrently connected network models with pinwheel-domain (ferret) or salt-and-pepper (mouse) organization. This model proposed that glutamate uptake shapes information representation when it affects the contribution of excitatory and inhibitory neurons to the network activity. Namely, strengthening the contribution of excitatory neurons generally broadens tuning and elevates the response. In contrast, strengthening the contribution of inhibitory neurons can have a sharpening effect on tuning. In addition local representational topology also plays a role: In the pinwheel-domain model effects were strongest within domains - regions where neighboring neurons share preferred orientations. Around pinwheels but also within salt-and-pepper networks the effects were less strong. Our model proposes that the pharmacological intervention in ferret increases the contribution of excitatory cells, while the reduced expression in mouse increases the contribution of inhibitory cells to network activity.
The distribution of recurrence times or return intervals between extreme events is important to characterize and understand the behavior of physical systems and phenomena in many disciplines. It is well known that many physical processes in nature and society display long range correlations. Hence, in the last few years, considerable research effort has been directed towards studying the distribution of return intervals for long range correlated time series. Based on numerical simulations, it was shown that the return interval distributions are of stretched exponential type. In this paper, we obtain an analytical expression for the distribution of return intervals in long range correlated time series which holds good when the average return intervals are large. We show that the distribution is actually a product of power law and a stretched exponential form. We also discuss the regimes of validity and perform detailed studies on how the return interval distribution depends on the threshold used to define extreme events.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
