Synaptic strength

One of the most fundamental tenets in neuroscience is that information is stored in the strength of synapses, and that learning relies on changes in synaptic strength. Here we aim to extend this tenet into the temporal domain by proposing that synapses not only learn to strengthen or weaken, but can learn when to be weak or strong on the subsecond scale. It has been known for more than half a century that synapses exhibit short-term synaptic plasticity (STP): a form of presynaptic, use-dependent, plasticity in which consecutive spikes can elicit progressively depressing (short-term depression/

Memory and learning are significantly influenced by long-term changes in synaptic strength, though the exact molecular mechanisms remain unclear. The postsynaptic density (PSD) is a critical component for storing and organizing synaptic long-term changes. The PSD itself is organized into complex nano-clusters, which are modulated during synaptic plasticity. However, the underlying organizational principles yielding such changes and maintaining stability otherwise are still to a large degree unknown. Recent research assumes that liquid-liquid phase separation (LLPS) might be crucial for PSD for

…fluctuations in membrane potential and synaptic strength $^{4

…Synaptic strength is proportional to the number of AMPARs in the postsynaptic membrane. Previous models of AMPA receptor trafficking can explain their fast, brief incorporation in dendritic spines after LTP induction but offer limited insights into long-lasting changes in AMPAR content at potentiated spines[1,2]. Hence, a unified modeling framework is necessary to understand persistent synaptic changes in AMPAR numbers. Molecular trafficking, such as diffusion, active transport, endo/exocytos

Astrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites.D-serine is a co-agonist for the NMDA receptor regulating the strength and direction of synaptic plasti

Establishing, maintaining and dynamically modifying synaptic connections is a key principle of neuronal computations. The underlying molecular resource of these processes is synaptic proteins. Tight control of protein levels across neurons is crucial to ensure synaptic function. Changes in the synaptic proteome have been associated with compromised synaptic function and in severe cases various diseases. Among the major factors in regulating protein levels are thought to be protein synthesis, trafficking and degradation. While there is substantial literature on protein synthesis, both trafficki

Long-term depression (LTD) is an activity-dependent decrease of synaptic strength. This depressed state is transient, initiating either a re-potentiation or suppression, referred to as pruning, of the synapse within hours to days following the LTD induction. Nevertheless, the precise relationship between LTD and synaptic pruning remains incompletely elucidated. Through the integration of various imaging techniques and electrophysiology, we have identified essential factors that link NMDAR-dependent LTD to synaptic pruning. The molecular alterations pivotal for the induction of LTD must persist

The actin-cytoskeleton is an essential structural component of all mammalian cells, and involves the constant dynamic cycling between actin monomers and filaments, a process mediated by numerous actin-associated proteins[1]. Tropomyosins are actin-associated proteins that form co-polymers with actin filaments. Here, we aim to determine tropomyosin isoform-specific properties in the brain[2]. We report the expression, localisation and physiological function of various tropomyosin isoforms (and by proxy, their actin filaments) in mouse primary neurons, astrocytes and microglia – with a focus on

Which nodes in a brain network causally influence one another, and how do such interactions utilize the underlying structural connectivity? One of the fundamental goals of neuroscience is to pinpoint such causal relations. Conventionally, these relationships are established by manipulating a node while tracking changes in another node. A causal role is then assigned to the first node if this intervention led to a significant change in the state of the tracked node. In this presentation, I use a series of intuitive thought experiments to demonstrate the methodological shortcomings of the curren

…during development through the strengthening of synapses between neurons with similar functional preferences. This raises the hypothesis that the strength of synapses should correlate with the difference in functional preference between pre- and postsynaptic activity. A recent study, however, found that the functional preference of cortical neurons was correlated with the number of spines a

…sensory learning can selectively alter synaptic strength. I will discuss recent findings that differentiate reinforcement learning from sensory experience, showing rapid and selective plasticity of thalamic and inhibitory synapses within primary sensory cortex.

Spike Timing Dependent Plasticity (STDP) is argued to modulate synaptic strength depending on the timing of pre- and postsynaptic spikes. Physiological experiments identified a variety of temporal kernels: Hebbian, anti-Hebbian and symmetrical LTP/LTD. In this work we present a novel plasticity model, the Voltage-Dependent Pathway Model (VDP), which is able to replicate those distinct kernel types and intermediate versions with varying LTP/LTD ratios and symmetry features. In addition, unlike previous models it retains these characteristics for different neuron models, which allows for compari

…The increase and decrease in synaptic strength, mediated through the structural plasticity of the spine, are important for learning, memory, and cognitive function. Dendritic spines are small structures that contain the synapse. They come in a variety of shapes (stubby, thin, or mushroom-shaped) and a wide range of sizes that protrude from the dendrite. These spines are the regions where the postsynaptic biochemical machinery responds to the neurotransmitters. Spines are dynamic s