PSD-95

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

Postsynaptic density protein 95 (PSD-95) is an important signalling scaffold of the PSD of excitatory synapses. We have previously shown that PSD-95 dependent silent synapse maturation closes the critical period (CP) for ocular dominance plasticity in mouse V1: PSD-95 KO mice display both functional & structural hallmarks of CP plasticity and synapses cannot properly stabilize. Since the development of binocularity happens during the CP, we hypothesized that PSD-95 KOs should display compromised binocular integration. To test this hypothesis, we performed both behavioural experiments and m

Cypin (cytosolic PSD-95 interactor) is the most highly expressed guanine deaminase in the brain. Cypin regulates neuronal development by increasing dendritogenesis, modifying dendritic spine morphology, and protecting neurons from injury. To identify binding partners to cypin that may act to mediate these functions, we performed a yeast two-hybrid screen of a rat brain cDNA library with cypin as bait. One of the interactors identified is the beta 7 subunit of the proteasome. Using ubiquitin-independent and ubiquitin-dependent sensors in cultured cells, we found that cypin acts via both pathway

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

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by impairments in social behavior and communication. Traditional research on the biology of ASDs has focused on the central nervous system (CNS), aiming to identify brain regions, molecular mechanisms, and genetic mutations associated with ASDs. However, an increasingly holistic approach to ASDs demonstrated that there is comorbidity with immune and gastrointestinal (GI) dysfunctions. It is now accepted that there is a bidirectional communication between the gut and the brain, with the microbiota play

There is strong evidence that alterations in the structural and functional properties of synaptic connections during learning are underlying the formation of long-term memories. However, what specific changes in the architecture of the neuronal network are mediated by learning-induced plasticity is still poorly understood. A major limiting factor of current in vivo imaging studies of synaptic dynamics is that typically only at a small number of synapses are assessed in a given animal, typically tens to hundreds. Here, we started to apply longitudinal in vivo two-photon imaging of more than a m

Severe bacterial infections affect more than 19 million people each year. With improved treatment strategies, more and more patients survive such severe bacterial infections. However, the majority of these survivors develop cognitive impairment and mental health problems. The pathogenesis of infection-induced cognitive impairment may include vascular injuries and neuro-inflammation, which eventually leads to neuron dysfunction. However, the mechanisms that promote cognitive impairment post infection remain largely unknown. We observed that mice exhibit hippocampus-dependent memory impairment p

Immunoglobulin superfamily member 9b (IgSF9b) is a cell adhesion protein that has been linked to the etiology of several psychiatric disorders, including bipolar disorder and schizophrenia. Based on previous studies in neuronal cultures, IgSF9b was proposed to specifically regulate the structure and function of GABAergic synapses in the brain through an indirect interaction with the synaptic adhesion protein Neuroligin-2. To date, however, very little is known about the expression pattern of IgSF9b in the intact brain, and the synaptic localization of IgSF9b in different brain regions has neve

…in our laboratory implies that PSD-95 (postsynaptic density protein 95)-dependent synaptic plasticity in dCA1 area is required for updating of contextual fear memory.To check how inactivation of dCA1 area affects contextual fear memory extinction, we stereotactically injected the adenoviral vectors (AAVs) encoding DREADD receptor hM4 [AAV2.1:hSyn_hM4_mCherry]. Next we trained mice in contextual fear conditioning (CFC). We found that chemogenetic inhibition

…forming a ternary complex with the PSD-95 and GluN2A subunit of the receptor. This complex is needed for long-term potentiation induction and NMDAR-dependent hippocampal behaviors, such as spatial learning. Rph3A overexpression increases dendritic spine density and GluN2A-containing NMDARs at synaptic membranes. Overall, these results suggest that

Apolipoprotein E (ApoE) is the major glycoprotein in the brain and plays a critical role in the transport of cholesterol and other lipids. Besides, ApoE has a crucial function in the maintenance of synaptodendritic connections, and repair of neurons. ApoE knockout (ApoE-KO) mice model whose apoE gene has been knocked out has great importance for understanding the effect of ApoE and loss of function of ApoE. Scientists have reported cognitive impairment in ApoE-KO mice, with cholinergic deficits, decreased synaptic excitability. In the present study, we investigated the difference between the b

Synapses are established and maintained by adhesion molecules, which include post-synaptic neuroligins (NLGNs). In the absence of highly specific antibodies, the sub-cellular distribution and synaptic function of NLGNs have been extensively manipulated using knock-out, over-expression or rescues approaches, leading to controversial results. In this context, we generated a new transgenic knock-in mouse strain in which endogenous NLGN1 has been N-terminally tagged with a biotin acceptor peptide (bAP) by gene editing using the CRISPR-Cas-9 strategy. Native NLGN1 can be enzymatically biotinylated