Activation of NMDA receptors in hippocampal area CA1 by low and high frequency orthodromic stimulation and their contribution to induction of long-term potentiation

Shankar, Subbakrishna, Timothy J. Teyler, and Norman Robbins. Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1. J. Neurophysiol. 79: 334–341, 1998. Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 in the hippocampus was shown to consist of N-methyl-d-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 μM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 μM d,l-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40–60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.

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Interaction between paired-pulse facilitation and long-term potentiation in the projection from hippocampal area CA1 to the subiculum

Neuroreport ◽

10.1097/00001756-199812210-00019 ◽

1998 ◽

Vol 9 (18) ◽

pp. 4109-4113 ◽

Cited By ~ 36

Author(s):

Sean Commins ◽

John Gigg ◽

Michael Anderson ◽

Shane M. OʼMara

Keyword(s):

Long Term Potentiation ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Area Ca1 ◽

Term Potentiation ◽

Hippocampal Area

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Cell-Permeable Scavengers of Superoxide Prevent Long-Term Potentiation in Hippocampal Area CA1

Journal of Neurophysiology ◽

10.1152/jn.1998.80.1.452 ◽

1998 ◽

Vol 80 (1) ◽

pp. 452-457 ◽

Cited By ~ 109

Author(s):

Eric Klann

Keyword(s):

Nmda Receptor ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Receptor Activation ◽

Manganese Porphyrin ◽

Area Ca1 ◽

Term Potentiation ◽

Hippocampal Area ◽

Nmda Receptor Activation

Klann, Eric. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J. Neurophysiol. 80: 452–457, 1998. Long-term potentiation (LTP) in hippocampal area CA1 is generally dependent on N-methyl-d-aspartate (NMDA) receptor activation. Reactive oxygen species (ROS), including superoxide, are produced in response to NMDA receptor activation in a number of brain regions, including the hipppocampus. In this study, two cell-permeable manganese porphyrin compounds that mimic superoxide dismutase (SOD) were used to determine whether production of superoxide is required for the induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal slices with either Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the induction of LTP. Incubation of slices with either light-inactivated MnTBAP or light-inactivated MnTMPyP had no effect on induction of LTP. Neither MnTBAP nor MnTMPyP was able to reverse preestablished LTP. These observations suggest that production of superoxide occurs in response to LTP-inducing stimulation and that superoxide is necessary for the induction of LTP.

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Lead inhibited N-methyl-d-aspartate receptor-independent long-term potentiation involved ryanodine-sensitive calcium stores in rat hippocampal area CA1

Neuroscience ◽

10.1016/j.neuroscience.2005.12.033 ◽

2006 ◽

Vol 139 (2) ◽

pp. 463-473 ◽

Cited By ~ 14

Author(s):

X.M. Li ◽

Y. Gu ◽

J.Q. She ◽

D.M. Zhu ◽

Z.D. Niu ◽

...

Keyword(s):

Long Term Potentiation ◽

Calcium Stores ◽

Aspartate Receptor ◽

Area Ca1 ◽

Term Potentiation ◽

Hippocampal Area

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Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat

Journal of Neurophysiology ◽

10.1152/jn.00780.2011 ◽

2012 ◽

Vol 107 (3) ◽

pp. 902-912 ◽

Cited By ~ 24

Author(s):

Guan Cao ◽

Kristen M. Harris

Keyword(s):

Synaptic Plasticity ◽

Developmental Regulation ◽

Late Phase ◽

Long Term Potentiation ◽

Excitatory Synapses ◽

Developmentally Regulated ◽

Area Ca1 ◽

Term Potentiation ◽

Hippocampal Area

Long-term potentiation (LTP) is a form of synaptic plasticity thought to underlie memory; thus knowing its developmental profile is fundamental to understanding function. Like memory, LTP has multiple phases with distinct timing and mechanisms. The late phase of LTP (L-LTP), lasting longer than 3 h, is protein synthesis dependent and involves changes in the structure and content of dendritic spines, the major sites of excitatory synapses. In previous work, tetanic stimulation first produced L-LTP at postnatal day 15 (P15) in area CA1 of rat hippocampus. Here we used a more robust induction paradigm involving theta-burst stimulation (TBS) in acute slices and found the developmental onset of L-LTP to be 3 days earlier at P12. In contrast, at P8–11, TBS only reversed the synaptic depression that occurs from test-pulse stimulation in developing (P8–15) hippocampus. A second bout of TBS delivered 30–180 min later produced L-LTP at P10–11 but not at P8–9 and enhanced L-LTP at P12–15. Both the developmental onset and the enhanced L-LTP produced by repeated bouts of TBS were blocked by the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonovaleric acid. Thus the developmental onset age is P12 for L-LTP induced by the more robust and perhaps more naturalistic TBS induction paradigm. Metaplasticity produced by repeated bouts of TBS is developmentally regulated, advancing the capacity for L-LTP from P12 to P10, but not to younger ages. Together these findings provide a new basis from which to investigate mechanisms that regulate the developmental onset of this important form of synaptic plasticity.

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