N-Methyl-D-aspartate receptors are clustered and immobilized on dendrites of living cortical neurons.

Benke, Timothy A.; Jones, Owen; Collingridge, Graham L.; Angelides, Kimon J.

doi:10.1073/pnas.90.16.7819

Cited by 80 publications

(43 citation statements)

References 27 publications

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“…The significant block of the stereocilia TNP-ATP binding (57%) by suramin is highly suggestive of specific binding of the TNP-ATP to P, purinoceptors localized to this region. The level of block obtained with suramin is comparable .to that achieved in a recent imaging study localizing NMDA receptors to isolated neurons (Benke et al, 1993) utilizing a fluorescent derivative of conotoxin-G (CntxG), with specific block achieved with a thousand-fold excess of native CnTxG. In the present study, a caveat to the evidence for P, purinoceptor localization to the stereocilia of hair cells is the possibility of undetermined (nonspecific) interactions of TNP-ATP with the glycocalyx of the hair cells, given previous evidence for attraction of charged molecules by this region (see Santi and Anderson, 1987, for a review).…”

Section: Discussionsupporting

confidence: 59%

Fluorescence imaging of extracellular purinergic receptor sites and putative ecto-ATPase sites on isolated cochlear hair cells

1994

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Fluorescence imaging of extracellular adenosine-5′-triphosphate (ATP) binding sites on inner and outer hair cells isolated from the guinea pig organ of Corti was achieved using the fluorescent analog of ATP, 2′- (or-3′)-O-(trinitrophenyl)adenosine-5′- triphosphate (TNP-ATP; 30–75 microM). This analog, which fluoresces on binding to these sites, was pressure applied by micropipette while hair cells were viewed by fluorescence microscopy. Fluorescence imaging revealed a widespread distribution of extracellular binding sites, including the stereocilia, cuticular plate, and the basolateral margins of the cells, but particularly in infracuticular and infranuclear regions. In support of extracellular binding, simultaneous electrophysiological recordings demonstrated that rapid washout of TNP-ATP-induced fluorescence was dependent upon cell integrity. Suramin, a nonselective P2 purinoceptor antagonist, coapplied with TNP-ATP, reduced the fluorescence observed on the stereocilia and apical surface of the cuticular plate only. This implies that binding sites on the apical surface of hair cells are P2 receptors, consistent with previous electrophysiological evidence for localization of P2 receptors to the apical surface of cochlear hair cells (Housley et al., 1992). Binding of TNP-ATP to P2 purinoceptors was confirmed by its antagonism of the inward current elicited by ATP (10 microM) in voltage-clamped hair cells. Fluorescence from the basolateral margin was significantly quenched when TNP-ATP was applied in divalent cation-free solution. Because divalent cations are required for ATPase activity, this finding provides evidence for the presence of ecto-ATPases on the basolateral membrane of hair cells. The divalent cation-free condition had no significant effect on the ATP-gated P2 purinoceptor conductance. We propose that there are two classes of ATP binding sites on cochlear hair cells: apically located P2 purinoceptors gating nonselective cation channels and basolaterally located ecto- ATPases that may be involved in purine turnover.

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Section: Discussionsupporting

confidence: 59%

Fluorescence imaging of extracellular purinergic receptor sites and putative ecto-ATPase sites on isolated cochlear hair cells

1994

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“…The demonstration of NMDA receptor channels in the dendrites of CA3 pyramidal neurons was surprising in view of the fact that binding studies had indicated that these dendrites are devoid of NMDA receptors in the region of MF termination (Monaghan, Holets, Toy & Cotman, 1983;Benke, Jones, Collingridge & Angelides, 1993 (Jahr, 1992;Rosenmund, Clements & Westbrook, 1993;Hessler, Shirke & Malinow, 1993), and a mean quantal conductance change of 350 pS for the AMPA receptor-mediated EPSC (Jonas et al 1993). Assuming that the glutamate pulse in the synaptic cleft is roughly equivalent to the 1 ms pulse of 1 mim glutamate used in the present experiments (Clements et al 1992;see Jonas & Spruston, 1994 (Silver, Traynelis & Cull-Candy, 1992;Stern et al 1992b).…”

Section: Discussionmentioning

confidence: 99%

Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons.

Spruston

Jónás

Sakmann

1995

The Journal of Physiology

426

371

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1. Properties of dendritic glutamate receptor (GluR) channels were investigated using fast application of glutamate to outside-out membrane patches isolated from the apical dendrites of CA3 and CAl pyramidal neurons in rat hippocampal slices. CA3 patches were formed (15-76 ,um from the soma) in the region of mossy fibre (MF) synapses, and , suggesting that the fast and slow components were mediated by the GluR channels of the L-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and NMDA type, respectively. The peak amplitude ratio of the NMDA to AMPA receptormediated components varied between 0 03 and 0-62 in patches from both CA3 and CAl dendrites. Patches lacking either component were rarely observed. 3. The peak current-voltage (I-V) relationship of the fast component was almost linear, whereas the I-V relationship of the slow component showed a region of negative slope in the presence of 1 mm external Mg2+. The reversal potential for both components was close to 0 mV. 4. Kainate-preferring GluR channels did not contribute appreciably to the response to glutamate. The responses to 100 ms pulses of 1 mm glutamate were mimicked by application of 1 mm AMPA, whereas 1 mm kainate produced much smaller, weakly desensitizing currents. This suggests that the fast component is primarily mediated by the action of glutamate on AMPA-preferring receptors. 5. The mean elementary conductance of AMPA receptor channels was about 10 pS, as estimated by non-stationary fluctuation analysis. The permeability of these channels to Ca2+ was low (-5 % of the permeability to Cs+).6. The elementary conductance of NMDA receptor channels was larger, with a main conductance state of about 45 pS. These channels were 3-6 times more permeable to Ca2+ than to Cs+. 7. AMPA receptor-mediated currents activated rapidly in response to 1 ms pulses of 1 mM glutamate and deactivated with a predominant, fast time constant and a smaller, slower component (T1 I 2 ms, T2 t 8 ms, contributing -80 and -20 % to the total decay amplitude, respectively). Desensitization of the current during a 100 ms pulse was best fitted by two time constants (T, t 10 ms, -60%; T2 t 34 ms, -%-40%).8. NMDA receptor-mediated currents in response to 1 ms pulses of 1 mm glutamate activated and deactivated much more slowly than AMPA receptor-mediated currents.The time course could be described by a single exponential rising phase (T -7 ms) followed by a double exponential decay ( t 200 ms, -80%; T2 % 1-3 s, -20%).

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“…MCPG is a broadly acting blocker for different types of metabotropic glutamate receptors. AMPA as well as NMDA receptors are located on the postsynaptic site of synapses (Benke et al, 1993;Craig et al, 1993), and they mediate postsynaptic transmission in the hippocampus (Bekkers and Stevens, 1989). Metabotropic glutamate receptors are present on the postsynaptic membrane, and their activation or blockade can alter calcium levels within hippocampal neurons (Baude et al, 1993;Frenguelli et al, 1993).…”

Section: Spinesmentioning

confidence: 99%

Afferent Innervation Influences the Development of Dendritic Branches and Spines via Both Activity-Dependent and Non-Activity-Dependent Mechanisms

Kossel

Williams

Schweizer³

et al. 1997

J. Neurosci.

129

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The present investigation uses an in vitro co-culture system to study the role of afferent innervation in early development and differentiation of hippocampal neurons. Our experiments indicate that the formation of two key morphological features, dendritic branches and dendritic spines, is induced by afferent innervation. Hippocampal neurons develop multiple dendritic branches and spines only when extensively innervated by living axonal afferents. No morphological changes occurred when hippocampal neurons were plated on other cell surfaces such as fixed axons or astrocytes. Furthermore, afferents exerted their effect locally on individual dendrites that they contacted. When one portion of the dendritic arbor of a neuron was contacted by afferents and the other portion was not, morphological effects were restricted to the innervated dendrites. Innervation of some of the dendrites on a neuron did not produce global effects throughout the neuron. Afferent-induced dendritic branching is independent of activity, since branch induction was unaffected by chronic application of TTX or glutamate receptor blockers. In contrast, the formation of dendritic spines is influenced by activity. The number of developing spines was reduced when TTX or a cocktail of three glutamate receptor blockers was applied. Blockade of individual AMPA, NMDA, or metabotropic glutamate receptors did not affect the number of spines. These results, taken together, demonstrate that afferents can have a prominent influence on the development of postsynaptic target cells via both activity-dependent and non-activity-dependent mechanisms, indicating the presence of multiple signals. Accordingly, this suggests an important interplay between pre-and postsynaptic elements early in development.

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N-Methyl-D-aspartate receptors are clustered and immobilized on dendrites of living cortical neurons.

Cited by 80 publications

References 27 publications

Fluorescence imaging of extracellular purinergic receptor sites and putative ecto-ATPase sites on isolated cochlear hair cells

Fluorescence imaging of extracellular purinergic receptor sites and putative ecto-ATPase sites on isolated cochlear hair cells

Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons.

Afferent Innervation Influences the Development of Dendritic Branches and Spines via Both Activity-Dependent and Non-Activity-Dependent Mechanisms

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