Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD

1992 ◽  
Vol 67 (4) ◽  
pp. 1009-1013 ◽  
Author(s):  
X. Xie ◽  
T. W. Berger ◽  
G. Barrionuevo
Keyword(s):  
Membrane Potential ◽  
Nmda Receptor ◽  
Cell Membrane ◽  
Synaptic Transmission ◽  
Granule Cell ◽  
Long Term Potentiation ◽  
Cell Membrane Potential ◽  
Synaptic Potentials ◽  
Synaptic Responses

1. The possibility of use-dependent, long-lasting modifications of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission was examined by intracellular recordings from granule cells of the hippocampal dentate gyrus in vitro. In the presence of the non-NMDA receptor antagonist 6-cyano-7-nitroquinaxaline-2,3-dione (CNQX, 10 microM) robust, long-term potentiation (LTP) of NMDA receptor-mediated synaptic potentials was induced by brief, high (50 Hz) and lower (10 Hz) frequency tetanic stimuli of glutamatergic afferents (60 +/- 6%, n = 8, P less than 0.001 and 43 +/- 12%, n = 3, P less than 0.05, respectively). 2. Hyperpolarization of granule cell membrane potential to -100 mV during 50-Hz tetanic stimuli reversibly blocked the induction of LTP (-6 +/- 2%, n = 6, P greater than 0.05) indicating that simultaneous activation of pre- and postsynaptic elements is a prerequisite for potentiation of NMDA receptor-mediated synaptic transmission. In contrast, hyperpolarization of the granule cell membrane potential to -100 mV during 10-Hz tetanic stimuli resulted in long-term depression (LTD) of NMDA receptor-mediated synaptic potentials (-34 +/- 8%, n = 8, P less than 0.01). 3. We also studied the role of [Ca2+]i in the induction of LTP and LTD of NMDA receptor-mediated synaptic responses. Before tetanization, [Ca2+]i was buffered by iontophoretic injections of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). BAPTA completely blocked the induction of LTP (3 +/- 5%, n = 13) and partially blocked LTD (-14.8 +/- 6%, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses

1993 ◽  
Vol 69 (5) ◽  
pp. 1774-1778 ◽  
Author(s):  
V. Crepel ◽  
C. Hammond ◽  
K. Krnjevic ◽  
P. Chinestra ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Input Resistance ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Bath Application ◽  
Synaptic Responses

1. The effects of an anoxic-aglycemic episode (1-3 min) on the pharmacologically isolated N-methyl-D-aspartate (NMDA)-mediated responses were examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anoxic-aglycemic episode induced a long term potentiation (LTP) of the NMDA receptor-mediated field excitatory post-synoptic potentials (EPSPs). This LTP, referred to as anoxic LTP, was observed in the presence of 1) a normal Mg2+ concentration [+40.1 +/- 5% (mean +/- SE)], 2) a low Mg2+ concentration (+52.2 +/- 10%), or 3) a Mg2+ free (+49 +/- 11%), 1 h after anoxia. 3. Bath application of D-2-amino-5-phosphonovaleric acid (D-APV, 20 microM, 15-21 min) before, during, and after the anoxic-aglycemic episode, which transiently blocked the synaptic NMDA receptor mediated response, prevented the induction of anoxic LTP. 4. The intracellularly recorded NMDA receptor-mediated EPSP was also persistently potentiated by anoxia-aglycemia (+47 +/- 4%). This potentiation was not associated with changes in membrane potential or input resistance. 5. These findings provide the first evidence that an anoxic-aglycemic episode induces an LTP of NMDA receptor-mediated responses. This potentiation may participate in the cascade of events that lead to delayed neuronal death.

Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus

Nature ◽  
1991 ◽  
Vol 349 (6305) ◽  
pp. 156-158 ◽  
Author(s):  
Zafar I. Bashir ◽  
Simon Alford ◽  
Stephen N. Davies ◽  
Andrew D. Randall ◽  
Graham L. Collingridge
Keyword(s):  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Term Potentiation

Evidence for NMDA and mGlu Receptor-Dependent Long-Term Potentiation of Mossy Fiber–Granule Cell Transmission in Rat Cerebellum

1999 ◽  
Vol 81 (1) ◽  
pp. 277-287 ◽  
Author(s):  
Egidio D'Angelo ◽  
Paola Rossi ◽  
Simona Armano ◽  
Vanni Taglietti
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Granule Cell ◽  
High Frequency ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Mglu Receptor ◽  
Rat Cerebellum ◽  
Term Potentiation

D'Angelo, Egidio, Paola Rossi, Simona Armano, and Vanni Taglietti. Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fiber–granule cell transmission in rat cerebellum. J. Neurophysiol. 81: 277–287, 1999. Long-term potentiation (LTP) is a form of synaptic plasticity that can be revealed at numerous hippocampal and neocortical synapses following high-frequency activation of N-methyl-d-aspartate (NMDA) receptors. However, it was not known whether LTP could be induced at the mossy fiber–granule cell relay of cerebellum. This is a particularly interesting issue because theories of the cerebellum do not consider or even explicitly negate the existence of mossy fiber–granule cell synaptic plasticity. Here we show that high-frequency mossy fiber stimulation paired with granule cell membrane depolarization (−40 mV) leads to LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a relatively hyperpolarized potential (−60 mV) or in the presence of NMDA receptor blockers [5-amino-d-phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl-Kyn)] prevented LTP, suggesting that the induction process involves a voltage-dependent NMDA receptor activation. Metabotropic glutamate receptors were also involved because blocking them with (+)-α-methyl-4-carboxyphenyl-glycine (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was expressed through an increase in both the NMDA and non-NMDA receptor-mediated current and by an NMDA current slowdown, suggesting that complex mechanisms control synaptic efficacy during LTP. LTP at the mossy fiber–granule cell synapse provides the cerebellar network with a large reservoir for memory storage, which may be needed to optimize pattern recognition and, ultimately, cerebellar learning and computation.

scholarly journals Astrocytic Neurexin-1 Orchestrates Functional Synapse Assembly

2020 ◽  
Author(s):  
Justin H. Trotter ◽  
Zahra Dargaei ◽  
Markus Wöhr ◽  
Kif Liakath-Ali ◽  
Karthik Raju ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Adhesion Molecule ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Synapse Ultrastructure ◽  
Alternatively Spliced ◽  
And Function ◽  
Dependent Mechanism ◽  
Synaptic Responses

ABSTRACTAt tripartite synapses, astrocytes surround synaptic contacts, but how astrocytes contribute to the assembly and function of synapses remains unclear. Here we show that neurexin-1α, a presynaptic adhesion molecule that controls synapse properties, is also abundantly expressed by astrocytes. Strikingly, astrocytic neurexin-1α, but not neuronal neurexin-1α, is highly modified by heparan sulfate. Moreover, astrocytic neurexin-1α is uniquely alternatively spliced and invariably contains an insert in splice-site #4, thereby restricting the range of ligands to which it binds. Deletion of neurexin-1 from astrocytes or neurons does not alter synapse numbers or synapse ultrastructure, but differentially impairs synapse function. At hippocampal Schaffer-collateral synapses, neuronal neurexin-1 is essential for normal NMDA-receptor-mediated synaptic responses, whereas astrocytic neurexin-1 is required for normal AMPA-receptor-mediated synaptic responses and for long-term potentiation of these responses. Thus, astrocytes directly shape synapse properties via a neurexin-1-dependent mechanism that involves a specific molecular program distinct from that of neuronal neurexin-1.

Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule

1990 ◽  
Vol 64 (3) ◽  
pp. 948-960 ◽  
Author(s):  
D. Jaffe ◽  
D. Johnston
Keyword(s):  
Nmda Receptor ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Postsynaptic Potentials ◽  
Voltage Gated ◽  
Term Potentiation ◽  
Ca2 Channels ◽  
Synaptic Responses

1. The induction of long-term potentiation (LTP) at hippocampal mossy-fiber synapses requires an increase in postsynaptic [Ca2+]i but is independent of N-methyl-D-aspartate (NMDA) receptor activation. Voltage-gated Ca2+ channels have been proposed as one alternative source for raising [Ca2+]i during the induction of LTP. We tested the hypothesis that voltage-gated Ca2+ channel activation could mediate the induction of LTP by examining whether 1) the induction of mossy-fiber LTP was dependent on postsynaptic depolarization and 2) depolarization alone, of a magnitude presumably capable of activating Ca2+ channels, was sufficient to induce LTP. 2. Intracellular recordings were made from rat CA3 pyramidal cells in the hippocampal slice preparation under both current- and voltage-clamp conditions. Mossy-fiber postsynaptic potentials and currents were recorded before and after high-frequency stimulation (HFS) in the presence of 20-50 microM D-2-amino-5-phosphonovaleric acid (D-APV), an NMDA-receptor antagonist. 3. Voltage clamping of CA3 neurons between -80 and -100 mV during HFS reversibly blocked the induction of mossy-fiber LTP. Conversely, HFS paired with depolarizing-current steps under current clamp increased the magnitude of LTP compared with controls. These results indicate that mossy-fiber LTP is dependent on postsynaptic depolarization, and presynaptic activation alone was not sufficient to induce mossy-fiber LTP. 4. Depolarizing-current injections, which presumably depolarized CA3 cells to potentials sufficient to activate voltage-gated Ca2+ channels, had no effect on mossy-fiber synaptic responses. These results suggest that synaptic activation, in addition to postsynaptic depolarization, is required for the induction of mossy-fiber LTP. 5. Single mossy-fiber afferent volleys were also paired with depolarizing-current pulses. In the presence of APV, pairing of single-mossy-fiber excitatory postsynaptic potentials (EPSPs) with postsynaptic depolarization did not potentiate synaptic responses, suggesting that some form of HFS is also required for mossy-fiber LTP. In the absence of APV, however, the contamination of mossy-fiber synaptic responses by CA3-recurrent inputs resulted in some potentiation. 6. These results suggest that the induction of mossy-fiber LTP is dependent on both pre- and postsynaptic activity and thus follows a Hebbian rule for synaptic modification. In contrast to that demonstrated at Schaffer-collateral-commissural synapses, however, the induction of mossy-fiber LTP may require HFS in addition to postsynaptic depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

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