Tuning synaptic strength by regulation of AMPA glutamate receptor localization.

Bioessays

Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.

Published: July 2024

Long-term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A combination of AMPAR structural data, super-resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever-clearer picture of how AMPARs are recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616278PMC
http://dx.doi.org/10.1002/bies.202400006DOI Listing

Publication Analysis

Top Keywords

excitatory synapses
8
tuning synaptic
4
synaptic strength
4
strength regulation
4
regulation ampa
4
ampa glutamate
4
glutamate receptor
4
receptor localization
4
localization long-term
4
long-term potentiation
4

Similar Publications

Neurocan regulates axon initial segment organization and neuronal activity.

Matrix Biol

January 2025

German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:

The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability.

View Article and Find Full Text PDF

Developing Topics.

Alzheimers Dement

December 2024

Acumen Pharmaceuticals, Charlottesville, VA, USA.

Background: Sabirnetug (ACU193) is a humanized IgG2 antibody targeting soluble, synaptotoxic amyloid β oligomers (AβOs). AβOs accumulate in Alzheimer's disease (AD) and induce pre- and post-synaptic changes, resulting in dendritic spine loss, neuronal degeneration, and release of synaptic proteins into the CSF. Recently, we reported that three administrations of sabirnetug in an early AD population (INTERCEPT-AD Phase 1 study, NCT04931459) significantly lowered CSF levels of the post-synaptic protein neurogranin as well as pTau181.

View Article and Find Full Text PDF

Background: Arc is a synaptic immediate early gene that mediates two distinct pathways at excitatory synapses. Canonically, Arc accelerates endocytosis of AMPA receptors by direct binding to TARPgs and endocytic machinery and thereby contributes to mGluR-LTD. Arc also acts at recently potentiated synapses, where it is phosphorylated by CaMKII and binds NMDAR subunits NR2A and NR2B and recruits the PI3K adaptor p55PIK to assemble a signaling complex that activates AKT and inhibits GSK3β.

View Article and Find Full Text PDF

Background: Deficits in interneuron and cholinergic circuits are noted in AD pathology, yet the precise mechanisms of their contribution to cognitive decline in the disease remain elusive. Neuronal Pentraxin 2 (NPTX2), a sensitive marker for synaptic activity and AD progression, is an immediate early gene expressed by pyramidal neurons that functions at excitatory synapses on Parvalbumin interneurons (PV-IN) to cluster AMPA receptors and strengthen circuit inhibition. NPTX2 is later shed from some synapses into the cerebrospinal fluid (CSF), where reduced NPTX2 levels inversely correlate with hippocampal volume and cognitive performance in individuals with AD/MCI.

View Article and Find Full Text PDF

Background: Chronic air pollution exposure increases accelerates cognitive aging and AD risk. Synapse loss in AD correlates with decreased cognitive ability. In rodents, inhaled air pollutants decreased glutamatergic synapses, decreasing excitatory postsynaptic currents (EPSCs), while increasing total levels of AMPA and NMDA receptor protein.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!