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ARTICLE, Behavioral/Systems

NMDA Receptors and L-Type Voltage-Gated Calcium Channels Contribute to Long-Term Potentiation and Different Components of Fear Memory Formation in the Lateral Amygdala

Elizabeth P. Bauer, Glenn E. Schafe and Joseph E. LeDoux
Journal of Neuroscience 15 June 2002, 22 (12) 5239-5249; https://doi.org/10.1523/JNEUROSCI.22-12-05239.2002
Elizabeth P. Bauer
1W. M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003
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Glenn E. Schafe
1W. M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003
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Joseph E. LeDoux
1W. M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003
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    Fig. 1.

    Pairing-induced LTP at thalamic input synapses in the LA is L-type VGCC dependent and NMDAR independent.A, Left, Schematic of the amygdala slice preparation, showing placement of stimulating and recording electrodes. Afferent fibers from the auditory thalamus enter the LA medially, coursing through the ventral most part of the striatum just above the central nucleus. Recordings were made just below the site of termination of auditory thalamic fibers terminating in the LA.CE, Central nucleus of amygdala; B, basal nucleus of amygdala; IC, internal capsule;OT, optic tract; EC, external capsule.Right, Example of the response of one cell to 10 stimuli delivered at 30 Hz paired with 1 nA, 5 msec depolarizations. This pairing was given 15 times at 10 sec intervals to induce LTP.B, Mean ± SE percentage of EPSP slope (relative to baseline) in cells treated with ACSF vehicle (n = 6; squares) or 50 μm verapamil (n = 5; triangles) before and after LTP induction by pairing at time 0. Traces (averages of 10 responses) from individual experiments before and 30 min after LTP induction are shown below. C, Mean ± SE percentage of EPSP slope (n = 5; squares) and amplitude (n = 4; triangles) relative to baseline before and after treatment with 50 μm verapamil at time 0. Traces (averages of 10 responses) are taken from an individual experiment before and 20 min after verapamil application. Inset, Mean ± SE integral under evoked EPSP (AUC) relative to baseline before and 20 min after verapamil application (n = 5).D, Mean ± SE percentage of EPSP slope (relative to baseline) in cells treated with ACSF vehicle (n = 8; squares) or 50 μm APV (n = 8; triangles) before and after LTP induction by pairing at time 0. Traces (averages of 10 responses) from individual experiments before and 30 min after LTP induction are shown below.

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    Fig. 2.

    Both tetanus-induced LTP and synaptic transmission at thalamic input synapses to LA are impaired by APV. A, Example of the response of one cell to 30 stimuli at 30 Hz. A tetanus of 100 stimuli at 30 Hz given twice was used to induce LTP.B, Mean ± SE percentage of EPSP slope (relative to baseline) in cells treated with ACSF vehicle (n = 7; squares) or 50 μm APV (n = 6; triangles) before and after LTP induction by a 30 Hz tetanus at time 0. Traces(averages of 10 responses) from individual experiments before and 30 min after LTP induction are shown below. C, Mean ± SE percentage of EPSP slope (n = 6;squares) and amplitude (n = 6;triangles) relative to baseline before and after treatment with 50 μm APV at time 0. Traces(averages of 10 responses) are taken from an individual experiment before and 30 min after APV application. Inset, Mean ± SE AUC (relative to baseline) before and 30 min after APV application (n = 6). *p < 0.05 relative to predrug AUC.

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    Fig. 3.

    Tetanus-induced LTP at thalamic input synapses is impaired by selective NR2B blockade but not by an L-type VGCC antagonist. A, Mean ± SE percentage of EPSP slope (relative to baseline) in cells treated with ACSF vehicle (n = 7; squares) or 10 μm of the selective NR2B antagonist ifenprodil (n = 6;triangles) before and after LTP induction by a tetanus at time 0. Traces (averages of 10 responses) from individual experiments before and 30 min after LTP induction are shown below. B, Mean ± SE percentage of EPSP slope (n = 6; squares) or amplitude (n = 6; triangles) relative to baseline before and after treatment with 10 μm ifenprodil at time 0. Traces (averages of 10 responses) are taken from an individual experiment before and 25 min after ifenprodil application. Inset, Mean ± SE AUC relative to baseline before and 25 min after ifenprodil application (n = 6). C, Mean ± SE percentage of EPSP slope (relative to baseline) in cells treated with ACSF vehicle (n = 7; squares) or 50 μm verapamil (n = 7;triangles) before and after LTP induction by a tetanus at time 0. Traces (averages of 10 responses) from individual experiments before and 30 min after LTP induction are shown below.

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    Fig. 4.

    Intra-LA infusion of an L-type VGCC antagonist dose-dependently impairs auditory fear conditioning. A, Schematic of behavioral protocol. B, Cannula tip placements from rats infused with dH2O (black squares), 0.04 μg of verapamil (white squares), 0.4 μg of verapamil (white circles), or 4 μg of verapamil (white triangles). Adapted fromPaxinos and Watson (1997). B, Basal nucleus of amygdala;CE, central nucleus of amygdala. C, Mean ± SE postshock freezing after the two conditioning trials in rats given intra-LA infusions of dH2O (vehicle;n = 10): 0.04 μg (n = 6), 0.4 μg (n = 8), or 4 μg (n = 9). D, Mean ± SE auditory fear memory 24 after conditioning in the same rats. *p < 0.05 relative to vehicle controls.

  • Fig. 5.
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    Fig. 5.

    Blockade of L-type VGCCs or NMDARs in the LA impairs memory formation of auditory fear conditioning in different ways. A, Schematic of behavioral protocol.B, Cannula tip placements from rats infused with dH2O (black squares), 4 μg of verapamil (white triangles), or 5 μg of APV (white circles). Adapted from Paxinos and Watson (1997).C, Mean ± SE postshock freezing between conditioning trials in rats given intra-LA infusions of dH2O (vehicle; n = 11), 4 μg of verapamil (n = 11), or 5 μg of APV (n = 8). D, Mean ± SE auditory fear memory assessed at 1 hr after conditioning in the rats fromC. E, Mean ± SE auditory fear memory assessed at 3 hr after conditioning in the rats fromC. F, Mean ± SE auditory fear memory assessed at 6 hr after conditioning in the rats fromC. G, Mean ± SE auditory fear memory assessed at 24 hr after conditioning in the rats fromC. Freezing during the 24 hr test is also expressed as a percentage of that during the 1 hr test (% of STM) for each rat (inset). *p < 0.05 relative to vehicle controls.

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The Journal of Neuroscience: 22 (12)
Journal of Neuroscience
Vol. 22, Issue 12
15 Jun 2002
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NMDA Receptors and L-Type Voltage-Gated Calcium Channels Contribute to Long-Term Potentiation and Different Components of Fear Memory Formation in the Lateral Amygdala
Elizabeth P. Bauer, Glenn E. Schafe, Joseph E. LeDoux
Journal of Neuroscience 15 June 2002, 22 (12) 5239-5249; DOI: 10.1523/JNEUROSCI.22-12-05239.2002

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NMDA Receptors and L-Type Voltage-Gated Calcium Channels Contribute to Long-Term Potentiation and Different Components of Fear Memory Formation in the Lateral Amygdala
Elizabeth P. Bauer, Glenn E. Schafe, Joseph E. LeDoux
Journal of Neuroscience 15 June 2002, 22 (12) 5239-5249; DOI: 10.1523/JNEUROSCI.22-12-05239.2002
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Keywords

  • fear conditioning
  • APV
  • ifenprodil
  • verapamil
  • LTP
  • amygdala

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