Search results for "Synaptic scaling"
showing 8 items of 8 documents
GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse
2017
Summary Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1) binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9) is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption…
The stressed cytoskeleton: How actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior
2015
Stress alters synaptic plasticity but the molecular and cellular mechanisms through which environmental stimuli modulate synaptic function remain to be elucidated. Actin filaments are the major structural component of synapses and their rearrangements by actin-binding proteins (ABPs) are critical for fine-tuning synaptic plasticity. Accumulating evidence suggests that some ABPs are specifically regulated by stress and stress-related effectors such as glucocorticoids and corticotropin releasing hormone. ABPs may thus be central in stress-induced perturbations at the level of synaptic plasticity, leading to impairments in behavioral domains including cognitive performance and social behavior.…
Synaptic scaling generically stabilizes circuit connectivity
2011
Neural systems regulate synaptic plasticity avoiding overly strong growth or shrinkage of the connections, thereby keeping the circuit architecture operational. Accordingly, several experimental studies have shown that synaptic weights increase only in direct relation to their current value, resulting in reduced growth for stronger synapses [1]. It is, however, difficult to extract from these studies unequivocal evidence about the underlying biophysical mechanisms that control weight growth. The theoretical neurosciences have addressed this problem by exploring mechanisms for synaptic weight change that contain limiting factors to regulate growth [2]. The effectiveness of these mechanisms i…
Targeted rescue of synaptic plasticity improves cognitive decline after severe systemic inflammation
2021
AbstractSepsis-associated encephalopathy (SAE) is a frequent complication in patients with severe systemic infection resulting in acute brain dysfunction and incapacitating long-term sequelae. SAE includes delirium, premature death, post-traumatic stress disorder, and major long-term cognitive impairment. The underlying pathophysiology of SAE is largely unresolved and specific treatment options are missing. We induced the peritoneal contamination and infection (PCI) sepsis model in 769 mice and compared these with 259 control mice. We found that experimental sepsis causes synaptic pathology in the brain characterized by severely disordered synaptic plasticity with reduced long-term potentia…
Synaptic Scaling Enables Dynamically Distinct Short- and Long-Term Memory Formation
2013
Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling – a slow process usually associated with the maintenance of activity homeostasis – combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The inter…
Self-organization of Computation in Neural Systems
2015
When learning a complex task our nervous system self-organizes large groups of neurons into coherent dynamic activity patterns. During this, a cell assembly network with multiple, simultaneously active, and computationally powerful assemblies is formed; a process which is so far not understood. Here we show that the combination of synaptic plasticity with the slower process of synaptic scaling achieves formation of such assembly networks. This type of self-organization allows executing a difficult, six degrees of freedom, manipulation task with a robot where assemblies need to learn computing complex non-linear transforms and - for execution - must cooperate with each other without interfer…
Synaptopodin regulates denervation-induced homeostatic synaptic plasticity
2013
Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-de…
Presynaptic CB1 Receptors Regulate Synaptic Plasticity at Cerebellar Parallel Fiber Synapses
2011
Endocannabinoids are potent regulators of synaptic strength. They are generally thought to modify neurotransmitter release through retrograde activation of presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs regulate several forms of synaptic plasticity at synapses onto Purkinje cells, including presynaptically expressed short-term plasticity and, somewhat paradoxically, a postsynaptic form of long-term depression (LTD). Here we have generated mice in which CB1Rs were selectively eliminated from cerebellar granule cells, whose axons form parallel fibers. We find that in these mice, endocannabinoid-dependent short-term plasticity is eliminated at parallel fiber…