Long-term potentiation and functional synapse induction in developing hippocampus

Durand, Guylaine M.; Kovalchuk, Yury; Konnerth, Arthur

doi:10.1038/381071a0

Cited by 715 publications

(614 citation statements)

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“…One can therefore surmise that spine structures are a key determinant of synaptic efficacy via control of the distribution of the AMPA receptors 9,10,43 . In addition, our study suggests that thin spines and filopodia may be postsynaptic components of silent synapses 28,32,34,44 . This might result from less effective transport of AMPA receptors into thinner spines with smaller volume-to-surface ratios.…”

Section: Discussionmentioning

confidence: 60%

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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/ spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.Most excitatory synaptic transmission in the mammalian central nervous system relies on glutamate as a neurotransmitter, and postsynaptic glutamate receptors are central in both the acquisition and maintenance of memory 1, 2 . Substantial biochemical evidence indicates that glutamate receptors in postsynaptic densities (PSDs) are regulated by various protein machineries that link the receptors to the cytoskeleton 3,4,5 and that control the insertion [6][7][8][9][10] and phosphorylation of the receptors 11,12 . Individual dendritic spines have been thought to act as functional compartments of glutamate receptor expression, given that they are physically and thus metabolically separated from the body of the dendrite by the narrow spine neck [13][14][15][16] . Indeed, the Hebbian principle of learning as well as most theories of neuronal networks assume that the strength of synaptic connections is subject to independent control 17 . Moreover, spine geometry has been proposed to be a key determinant of synaptic function and memory in the brain 13, 14, 18-22 . Correspondence to: Haruo Kasai. These various hypotheses have not been tested experimentally, however, because it is not possible to systematically investigate postsynaptic glutamate sensitivities at the level of the individual spine by classical electrophysiological approaches 16,23 . Also, the number of functional AMPA-sensitive glutamate receptors in individual spines has not been estimated directly. Two-photon excitation of caged-glutamate compounds may overcome these difficulties 24 as a result of the inherent three-dimensional resolution of neurotransmitter application associated with this technique. However, caged-glutamate compounds with a cross-section for two-photon absorption, a rate of photolysis, and a stability in aqueous solution sufficient for such studies have not previously been described [25][26][27] . NIH Public AccessWe developed a caged-glutamate compound and microscopic system for two-photon excitation that allowed systematic investigation of functional glutamate receptors at the level of the individual synapse. Our experiment...

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Section: Discussionmentioning

confidence: 60%

“…4kn = 7). In young animals (7 to 9 days old), dendrites were decorated only sparsely with spines 34 , and most of the dendritic shaft was devoid of glutamate sensitivity (Fig. 4l), although marked expression of functional AMPA receptors was already apparent in mushroom spines present (Fig.…”

Section: Distribution Of Functional Ampa Receptors In Vivomentioning

confidence: 98%

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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“…The earliest stages in synapse structural development may vary (Vaughn, 1989); in hippocampal neurons in vitro, the earliest synaptic contacts lack a distinct PSD and have vesicles of variable forms (Ahmari et al, 2000;Ziv and Garner, 2004). Furthermore, spine synapses, typical of adult glutamatergic synapses in the CA1stratum radiatum, are rare at P2, with most synapses formed directly on dendrite shafts (Fiala et al, 1998;Petralia et al, 2003); physiological studies confirm that functional glutamatergic synapses form directly on dendrite shafts of CA1 pyramidal neurons at P2 (Durand et al, 1996). Thus, the major characteristics of adult glutamatergic synapses of the CA1 stratum radiatum, including distinct PSDs, clusters of round vesicles, and synaptic spines, would not be expected features of nascent excitatory synapses.…”

Section: Mature Versus Immature Synaptic Contacts At Postnatal Daymentioning

confidence: 98%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

208

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In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

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“…During the first two weeks of development, the relative contribution of AMPARs to postsynaptic currents increases (Crair and Malenka, 1995;Durand et al, 1996;Hsia et al, 1998;Lu et al, 2001;Ye et al, 2005). To study the role of GluA4 in the AMPAfication of the glutamatergic synapses, we analyzed the amplitude ratio of the AMPAR-vs. NMDAR-mediated EPSCs in WT and GluA4-/-mice at different developmental stages ( Fig.…”

Section: Maturation Of Ampar-mediated Transmission Is Perturbed In Thmentioning

confidence: 99%

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

et al. 2017

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Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism driving functional development and maturation of glutamatergic synapses. At immature hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for synaptic reinforcement. However, the physiological significance and molecular determinants of this developmentally restricted form of plasticity are not known. Here we show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission. This effect depends on a novel mechanism involving the extreme C-terminal end of GluA4, which interacts with the membrane proximal region of the C-terminal domain to control GluA4 trafficking. In the absence of GluA4, strengthening of AMPAR-mediated transmission during postnatal development was significantly delayed. These data suggest that the GluA4-mediated activation of silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic circuitry during the critical period of experience-dependent fine-tuning.

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Long-term potentiation and functional synapse induction in developing hippocampus

Cited by 715 publications

References 23 publications

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

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