Synaptic AMPA Receptor Plasticity and Behavior
TL;DR: It is argued that monitoring and manipulating synaptic AMPAR trafficking represents an attractive means to study cognitive function and dysfunction in animal models.
About: This article is published in Neuron.The article was published on 2009-02-12 and is currently open access. It has received 945 citations till now. The article focuses on the topics: Metaplasticity & Synaptic augmentation.
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TL;DR: This review discusses International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
3,044 citations
Cites background from "Synaptic AMPA Receptor Plasticity a..."
...This plasticity has been the most widely studied form of LTP and has been posited as a cellular correlate underlying learning and memory (Kessels and Malinow, 2009)....
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TL;DR: This Perspective considers the rationale and evidence for the synaptic homeostasis hypothesis (SHY), and points to open issues related to sleep and plasticity.
1,565 citations
Cites background from "Synaptic AMPA Receptor Plasticity a..."
...GluA2-containing AMPARs are strongly involved in constitutive receptor cycling and synaptic depression, while GluA1-containing AMPARs are linked to synaptic potentiation (Kessels and Malinow, 2009)....
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...16 Neuron 81, January 8, 2014 ª2014 Elsevier Inc. for example, the insertion of GluA1-containing AMPAR during wake (Qin et al., 2005) and their removal during sleep (Lanté et al., 2011), as well as increases and decreases in a molecular hallmark of synaptic depression, dephosphorylation of GluA1containing AMPARs at Ser845 (Kessels and Malinow, 2009), with time spent in sleep and wake respectively (Hinard et al., 2012)....
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...The trafficking of GluA1-containing AMPA receptors (AMPARs) in and out of the synaptic membrane is considered a primary mechanism for the occurrence of synaptic potentiation and depression, respectively (Kessels and Malinow, 2009)....
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...…2005) and their removal during sleep (Lanté et al., 2011), as well as increases and decreases in a molecular hallmark of synaptic depression, dephosphorylation of GluA1containing AMPARs at Ser845 (Kessels and Malinow, 2009), with time spent in sleep and wake respectively (Hinard et al., 2012)....
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TL;DR: The mechanistic and functional principles that underlie the relationship between signalling and endocytosis in cell biology are becoming increasingly evident across many systems.
Abstract: Cell signalling and endocytic membrane trafficking have traditionally been viewed as distinct processes Although our present understanding is incomplete and there are still great controversies, it is now recognized that these processes are intimately and bidirectionally linked in animal cells Indeed, many recent examples illustrate how endocytosis regulates receptor signalling (including signalling from receptor tyrosine kinases and G protein-coupled receptors) and, conversely, how signalling regulates the endocytic pathway The mechanistic and functional principles that underlie the relationship between signalling and endocytosis in cell biology are becoming increasingly evident across many systems
1,093 citations
TL;DR: Treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants, and these new agents have also been shown to reverse the synaptic deficits caused by stress.
Abstract: Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function. Although current antidepressants, such as serotonin-reuptake inhibitors, produce subtle changes that take effect in weeks or months, it has recently been shown that treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants. Within a similar time scale, these new agents have also been shown to reverse the synaptic deficits caused by stress.
999 citations
TL;DR: Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses are focused on.
Abstract: The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled with the fact that the underlying circuitry is evolutionarily well conserved, make it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses.
949 citations
References
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TL;DR: The application of molecular cloning technology to the study of the glutamate receptor system has led to an explosion of knowledge about the structure, expression, and function of this most important fast excitatory transmitter system in the mammalian brain.
Abstract: The application of molecular cloning technology to the study of the glutamate receptor system has led to an explosion of knowledge about the structure, expression, and function of this most important fast excitatory transmitter system in the mammalian brain. The first functional ionotropic glutamate receptor was cloned in 1989 (Hollmann et al 1989) , and the results of this molecular-based approach over the past three years are the focus of this review. We discuss the implications of and the new questions raised by this work-which is probably only a glance at this fascinating and complex signaling system found in brains from the snails to man. Glutamate receptors are found throughout the mammalian brain, where they constitute the major excitatory transmitter system. The longest-known and best-studied glutamate receptors are ligand-gated ion channels, also called ionotropic glutamate receptors , which are permeable to cations. They have traditionally been classified into three broad subtypes based upon pharmaco logical and electrophysiological data: a-amino-3-hydroxy-5-methyl-4isoxazole propionate (AMPA) receptors, kainate (KA) receptors , and N-methyl-D-aspartate (NMDA) receptors. Recently, however, a family of G protein-coupled glutamate receptors , which are also called metabotropic glutamate or transl -aminocyclopentanel ,3-dicarboxylate (tACPD) recep tors, was identified (Sugiyama et al 1987) . (For reviews of the classification and the pharmacological and electrophysiological properties of glutamate receptors see Mayer & Westbrook 1987, Collingridge & Lester 1989, Honore 1989, Monaghan et al 1989, Wroblewski & Danysz 1 989, Hansen &
4,079 citations
"Synaptic AMPA Receptor Plasticity a..." refers background in this paper
...Four different genes (GluR1, GluR2, GluR3, and GluR4) encode AMPAR subunits (Hollmann and Heinemann, 1994; Wisden and Seeburg, 1993)....
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TL;DR: Reading is a need and a hobby at once and this condition is the on that will make you feel that you must read.
Abstract: Some people may be laughing when looking at you reading in your spare time. Some may be admired of you. And some may want be like you who have reading hobby. What about your own feel? Have you felt right? Reading is a need and a hobby at once. This condition is the on that will make you feel that you must read. If you know are looking for the book enPDFd the organization of behavior as the choice of reading, you can find here.
3,986 citations
"Synaptic AMPA Receptor Plasticity a..." refers background in this paper
...It is thought that experiences can modify synapses, favoring some neuronal pathways within a circuit and weakening others (Hebb, 1949)....
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TL;DR: This review examines the progress made over the century in understanding the time-dependent processes that create the authors' lasting memories.
Abstract: The memory consolidation hypothesis proposed 100 years ago by Muller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time-dependent processes that create our lasting memories.
3,902 citations
"Synaptic AMPA Receptor Plasticity a..." refers background in this paper
...The emotional charge of an experience has long been appreciated as a mechanism to facilitate learning and memory in order to shape our behavior and optimize the chances of survival (Christianson, 1992; McGaugh, 2000; Richter-Levin and Akirav, 2003)....
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TL;DR: This article showed that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning.
Abstract: Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA) and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation. We now report that chronic intraventricular infusion of D,L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage, without affecting visual discrimination learning, which is not. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis that LTP is involved in some, but not all, forms of learning.
3,488 citations