ArticleJournal of neurophysiology2009
PKA has a critical role in synaptic delivery of GluR1- and GluR4-containing AMPARs during initial stages of acquisition of in vitro classical conditioning.
Article in Journal of neurophysiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Posttranslational modifications of AMPA receptors in synaptic function and memory.Cellular and molecular life sciences : CMLS · 2026Review
- Differing Patterns of Ionotropic Glutamate Receptor Subunit Gene Expression in Paraventricular Hypothalamic Nucleus Subregions following Angiotensin II Hypertension in Male Mice and Female Mice with Advanced Ovarian Failure.Neuroendocrinology · 2026Article
- AMPA Receptors in Synaptic Plasticity, Memory Function, and Brain Diseases.Cellular and molecular neurobiology · 2025Review
- Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model.Molecular neurobiology · 2023Review
- Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits.Frontiers in neuroanatomy · 2020Article
- Input from the medial geniculate nucleus modulates amygdala encoding of fear memory discrimination.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Article
- Acoustic trauma slows AMPA receptor-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function.The Journal of physiology · 2016Article
- Coincidence detection in a neural correlate of classical conditioning is initiated by bidirectional 3-phosphoinositide-dependent kinase-1 signalling and modulated by adenosine receptors.The Journal of physiology · 2015Article
- Regulation of BDNF chromatin status and promoter accessibility in a neural correlate of associative learning.Epigenetics · 2015Article
- Cyclophilin D deficiency rescues Aβ-impaired PKA/CREB signaling and alleviates synaptic degeneration.Biochimica et biophysica acta · 2014Article
- Sequential delivery of synaptic GluA1- and GluA4-containing AMPA receptors (AMPARs) by SAP97 anchored protein complexes in classical conditioning.The Journal of biological chemistry · 2014Article
- Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary neurons and human SH-SY5Y neuroblastoma cells.International journal of molecular sciences · 2013Article
- Identification of a functionally distinct truncated BDNF mRNA splice variant and protein in Trachemys scripta elegans.PloS one · 2013Article
- Two-stage AMPA receptor trafficking in classical conditioning and selective role for glutamate receptor subunit 4 (tGluA4) flop splice variant.Journal of neurophysiology · 2012Article
- Rapid enrichment of presynaptic protein in boutons undergoing classical conditioning is mediated by brain-derived neurotrophic factor.Neuroscience · 2012Article
- Cloning and characterization of glutamate receptor subunit 4 (GLUA4) and its alternatively spliced isoforms in turtle brain.Journal of molecular neuroscience : MN · 2011Article
- Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Screening target specificity of siRNAs by rapid amplification of cDNA ends (RACE) for non-sequenced species.Journal of molecular neuroscience : MN · 2011Article
- Modeling signal transduction in classical conditioning with network motifs.Frontiers in molecular neuroscience · 2011Article
- Oligomeric amyloid-{beta} inhibits the proteolytic conversion of brain-derived neurotrophic factor (BDNF), AMPA receptor trafficking, and classical conditioning.The Journal of biological chemistry · 2010Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The cyclic AMP-dependent protein kinase (PKA) signaling pathway has been shown to be important in mechanisms of synaptic plasticity, although its direct and downstream signaling effects are not well understood. Using an in vitro model of eyeblink classical conditioning, we report that PKA has a critical role in initiating a signaling cascade that results in synaptic delivery of glutamate receptor 1 (GluR1)- and GluR4-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in abducens motor neurons during conditioning. PKA and the Ca(2+)-calmodulin-dependent protein kinases (CaMKs) II and IV are activated early in conditioning and are required for acquisition and expression of conditioned responses (CRs). cAMP-response-element-binding protein (CREB) is also activated early in conditioning but is blocked by coapplication of inhibitors to PKA and the CaMKs, suggesting that CREB is downstream of those signaling cascades. Moreover, evidence suggests that PKA activates extracellular signal-regulated kinase, which is also required for conditioning. Imaging studies after conditioning further indicate that colocalization of GluR1 AMPAR subunits with the synaptic marker synaptophysin requires PKA, but is insensitive to the N-methyl-d-aspartate receptor (NMDAR) inhibitor d,l-AP5. PKA activation also leads to synaptic localization of GluR4 subunits that, unlike GluR1, is dependent on NMDARs and is mediated by CaMKII. Together with previous studies, our findings support a two-stage model of AMPAR synaptic delivery during acquisition of classical conditioning. The first stage involves synaptic incorporation of GluR1-containing AMPARs that serves to activate silent synapses. This allows a second stage of NMDAR- and protein kinase C-dependent delivery of GluR4 AMPAR subunits that supports the acquisition of CRs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.