scholarly journals Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ning Zheng ◽  
Okunola Jeyifous ◽  
Charlotte Munro ◽  
Johanna M Montgomery ◽  
William N Green
Keyword(s):  
Long Term Potentiation ◽  
Receptor Trafficking ◽  
Synaptic Activity ◽  
Transferrin Receptors ◽  
Long Term Depression ◽  
Recycling Endosomes ◽  
Surface Receptors ◽  
Term Potentiation ◽  
Dependent Pathway

Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites.

scholarly journals Syndapin I Loss-of-Function in Mice Leads to Schizophrenia-Like Symptoms

2020 ◽  
Vol 30 (8) ◽  
pp. 4306-4324 ◽  
Author(s):  
Nicole Koch ◽  
Dennis Koch ◽  
Sarah Krueger ◽  
Jessica Tröger ◽  
Victor Sabanov ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Actin Dynamics ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
Long Term Depression ◽  
Membrane Recruitment ◽  
Term Potentiation

Abstract Schizophrenia is associated with cognitive and behavioral dysfunctions thought to reflect imbalances in neurotransmission systems. Recent screenings suggested that lack of (functional) syndapin I (PACSIN1) may be linked to schizophrenia. We therefore studied syndapin I KO mice to address the suggested causal relationship to schizophrenia and to analyze associated molecular, cellular, and neurophysiological defects. Syndapin I knockout (KO) mice developed schizophrenia-related behaviors, such as hyperactivity, reduced anxiety, reduced response to social novelty, and an exaggerated novel object response and exhibited defects in dendritic arborization in the cortex. Neuromorphogenic deficits were also observed for a schizophrenia-associated syndapin I mutant in cultured neurons and coincided with a lack of syndapin I–mediated membrane recruitment of cytoskeletal effectors. Syndapin I KO furthermore caused glutamatergic hypofunctions. Syndapin I regulated both AMPAR and NMDAR availabilities at synapses during basal synaptic activity and during synaptic plasticity—particularly striking were a complete lack of long-term potentiation and defects in long-term depression in syndapin I KO mice. These synaptic plasticity defects coincided with alterations of postsynaptic actin dynamics, synaptic GluA1 clustering, and GluA1 mobility. Both GluA1 and GluA2 were not appropriately internalized. Summarized, syndapin I KO led to schizophrenia-like behavior, and our analyses uncovered associated molecular and cellular mechanisms.

scholarly journals GluA1 trafficking and metabotropic NMDA: addressing results from other laboratories inconsistent with ours

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130145 ◽  
Author(s):  
Sadegh Nabavi ◽  
Rocky Fox ◽  
Stephanie Alfonso ◽  
Jonathan Aow ◽  
Roberto Malinow
Keyword(s):  
Fluorescent Protein ◽  
Long Term Potentiation ◽  
Long Term Depression ◽  
Mk 801 ◽  
Over Expression ◽  
Term Potentiation ◽  
The Difference ◽  
Green Fluorescent ◽  
Gfp Tag

We have previously shown that when over-expressed in neurons, green fluorescent protein (GFP) tagged GluA1 (GluA1-GFP) delivery into synapses is dependent on plasticity. A recent study suggests that GluA1 over-expression leads to its incorporation into the synapse, in the absence of additional long-term potentiation-like manipulations. It is possible that a GFP tag was responsible for the difference. Using rectification index as a measure of synaptic delivery of GluA1, we found no difference in the synaptic delivery of GluA1-GFP versus untagged GluA1. We recently published a study showing that while D-APV blocks NMDAr-dependent long-term depression (LTD), MK-801 and 7-chloro kynurenate (7CK) fail to block LTD. We propose a metabotropic function for the NMDA receptor in LTD induction. In contrast to our observations, recent unpublished data suggest that the above antagonists are equally effective in blocking LTD. We noticed different methodology in their study. Here, we show that their methodology has complex effects on synaptic transmission. Therefore, it is not possible to conclude that 7CK is effective in blocking LTD from their type of experiment.

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