Importance of AMPA Receptors for Hippocampal Synaptic Plasticity But Not for Spatial Learning

Zamanillo, Daniel; Sprengel, Rolf; Hvalby, Øivind; Jensen, Vidar R.; Burnashev, Nail; Rozov, Andrej; Kaiser, Katharina; Köster, Helmut Joachim; Borchardt, Thilo; Worley, Paul F.; Lübke, Joachim H. R.; Frotscher, Michael; Kelly, Peter H.; Sommer, Bernd; Andersen, P.; Seeburg, Peter H.; Sakmann, Bert

doi:10.1126/science.284.5421.1805

Cited by 730 publications

(810 citation statements)

References 48 publications

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“…In the hippocampus, LTP is dependent on increased insertion of the AMPA receptor subunit, GluR1 (Shi et al, 1999;Zamanillo et al, 1999). Previous studies found no detectable changes in the VTA in total cellular protein levels of GluR1 between cocaine-and saline-treated mice (Ungless et al, 2001).…”

Section: Resultsmentioning

confidence: 96%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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Section: Resultsmentioning

confidence: 96%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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“…For instance, Mayford et al (1996) showed in a learning task that the blockage of LTP in the hippocampus leads to a worse task performance compared to control. However, in a quite similar experimental setup the blockage of LTP leads to no significant differences (Zamanillo 1999). Regarding the neural correlate of memory, potential memory items were found, for example, in songbirds during song and recapitulation as stereotypical sequences of spike burst (Hahnloser et al 2002) or during a spatial task, as spatiotemporal patterns (Harris et al 2003) in the hippocampus.…”

Section: Links Between Time Scales Of Memory and Physiologymentioning

confidence: 90%

Time scales of memory, learning, and plasticity

et al. 2012

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If we stored every bit of input, the storage capacity of our nervous system would be reached after only about 10 days. The nervous system relies on at least two mechanisms that counteract this capacity limit: compression and forgetting. But the latter mechanism needs to know how long an entity should be stored: some memories are relevant only for the next few minutes, some are important even after the passage of several years. Psychology and physiology have found and described many different memory mechanisms, and these mechanisms indeed use different time scales. In this prospect we review these mechanisms with respect to their time scale and propose relations between mechanisms in learning and memory and their underlying physiological basis.

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“…GluA1 is dominant in activity-dependent recruitment of AMPARs to synapses. This is mediated by CaMKII phosphorylation of GluA1 and interaction with synaptic PDZ domaincontaining proteins that recruit and retain GluA1/GluA2 AMPARs at synapses during induction of long-term potentiation (LTP) 15,16 . Once the GluA1-mediated increase in AMPAR number is established, interactions with GluA2 take over to control constitutive and activity-dependent AMPAR endocytosis, and long-term depression (LTD) 10,17 .…”

Section: Subunit-specific Traffickingmentioning

confidence: 99%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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Importance of AMPA Receptors for Hippocampal Synaptic Plasticity But Not for Spatial Learning

Cited by 730 publications

References 48 publications

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Time scales of memory, learning, and plasticity

Synaptic AMPA receptor composition in development, plasticity and disease

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