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. 2005 Jun 15;25(24):5730-9.
doi: 10.1523/JNEUROSCI.0096-05.2005.

Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic plasticity in the fear system

Affiliations

Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic plasticity in the fear system

Annemieke M Apergis-Schoute et al. J Neurosci. .

Erratum in

  • J Neurosci. 2005 Jun 29;25(26):2 p following 6262

Abstract

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. In the first experiment, rats were given intrathalamic infusions of the MEK (mitogen-activated protein kinase-kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) before fear conditioning. Findings revealed that long-term memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1-3 h) of fear conditioning was intact. In the second experiment, rats received immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), or infusion of the protein synthesis inhibitor anisomycin. Posttraining infusion of either U0126 or DRB significantly impaired long-term retention of fear conditioning, whereas infusion of anisomycin had no effect. In the final experiment, rats received intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA). Findings revealed that thalamic infusion of U0126 impaired LTP in the LA. Together, these results suggest the possibility that MGm/PIN cells that project to the LA contribute to memory formation via ERK (extracellular signal-regulated kinase)-mediated transcription, but that they do so by promoting protein synthesis-dependent plasticity locally in the LA.

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Figures

Figure 1.
Figure 1.
Effects of pretraining intrathalamic infusion of U0126 on multiple-trial fear conditioning. a, Schematic of the behavioral protocol. Rats were given an intrathalamic infusion of 50% DMSO vehicle (n = 9) or one of two doses of U0126 (1.0 or 0.1 μg/side; n = 11 and 7, respectively) 30 min before five tone-shock pairings. They were then tested for retention of auditory fear conditioning at 1, 3, 6, and 24 h. b, Cannula placements in rats given intrathalamic infusion of 50% DMSO (vehicle; black squares), 1.0 μg of U0126 (white triangles), or 0.1 μg of U0126 (white circles). c, Mean ± SE postshock freezing between conditioning trials in rats given intrathalamic infusion of 50% DMSO (black squares), 1.0 μg of U0126 (white triangles), or 0.1 μg of U0126 (white circles). d, Mean ± SE auditory fear memory assessed at 1 h after conditioning in the rats from c. e, Mean ± SE auditory fear memory assessed at 3 h after conditioning in the rats from c. f, Mean ± SE auditory fear memory assessed at 6 h after conditioning in the rats from c. g, Mean ± SE auditory fear memory assessed at 24 h after conditioning in the rats from c. *p < 0.05 relative to vehicle (Veh).
Figure 2.
Figure 2.
Effects of pretraining intrathalamic infusion of U0126 on single-trial fear conditioning. a, Schematic of the behavioral protocol. Rats were given an intrathalamic infusion of 50% DMSO vehicle (n = 8) or the highest dose of U0126 (1.0 μg/side; n = 10) 30 min before one tone-shock pairing. They were then tested for retention of auditory fear conditioning 1 and 24 h after conditioning. b, Cannula placements in rats given an intrathalamic infusion of 50% DMSO vehicle (black squares) or U0126 (white triangles). c, Mean ± SE postshock freezing after the conditioning trial in rats given an intrathalamic infusion of 50% DMSO (black squares) or U0126 (white triangles). d, Mean ± SE auditory fear memory assessed at 1 h after conditioning in the rats from c. e, Mean ± SE auditory fear memory assessed at 24 h after conditioning in the rats from c. f, Mean ± SE auditory fear memory after reconditioning ∼1 week later. *p < 0.05 relative to vehicle.
Figure 3.
Figure 3.
Effects of immediate posttraining intrathalamic infusion of U0126, anisomycin, or DRB. a, Schematic of the behavioral protocol. Rats were given a single tone-shock pairing and then given an immediate intrathalamic infusion of 50% DMSO vehicle (n = 10), the highest dose of U0126 (1.0 μg/side; n = 9), the protein synthesis inhibitor anisomycin (62.5 μg/side; n = 10), or the mRNA synthesis inhibitor DRB (16 ng/side; n = 7). They were then tested for retention of auditory fear conditioning 24 h after conditioning. b, Cannula placements in rats given an intrathalamic infusion of 50% DMSO (vehicle; black squares), U0126 (white triangles), anisomycin (black circles), or DRB (gray triangles). c, Mean ± SE postshock freezing after the conditioning trial in rats given an intrathalamic infusion of 50% DMSO (black squares), U0126 (white triangles), anisomycin (black circles), or DRB (gray triangles). d, Mean ± SE auditory fear memory assessed at 24 h after conditioning in the rats from c. Aniso, Anisomycin. *p < 0.05 relative to vehicle.
Figure 4.
Figure 4.
Effects of intrathalamic infusion of U0126 on retrieval and reconsolidation of auditory fear conditioning. a, Schematic of reconsolidation behavioral protocol. Rats were trained with one tone-shock pairing. Twenty-four hours later, they received an intrathalamic infusion of 50% DMSO vehicle (n = 9) or the highest dose of U0126 (1 μg; n = 9) 30 min before a single tone retention (reactivation) test. They were then tested for retention of auditory fear conditioning at 3 and 24 h after the reactivation test. b, Cannula placements in rats given an intrathalamic infusion of 50% DMSO (vehicle; black squares) or U0126 (white triangles). c, Mean ± SE postshock freezing after the conditioning trial in vehicle controls (black squares) and U0126-treated rats (white triangles). d, Mean ± SE auditory fear memory assessed during the reactivation trial ∼24 h after training. e, Mean ± SE auditory fear memory assessed at 1 h after the reactivation trial (PR-STM). f, Mean ± SE auditory fear memory assessed at 24 h after the reactivation trial (PR-LTM).
Figure 5.
Figure 5.
Effects of intrathalamic infusion of U0126 on long-term potentiation in the LA. a, Illustration of cannula and electrode implantation. Rats were implanted with a glass recording pipette into the LA and a stimulation electrode into the MGm/PIN that was adhered to a stainless-steel infusion cannula. b, Schematic of experimental protocol. Rats received an infusion of 50% DMSO vehicle (n = 5) or U0126 (1.0 μg; n = 6) 30 min before LTP-inducing stimulation of the auditory thalamus. Baseline recordings were taken before and after the infusion, as well as after LTP induction (see Materials and Methods). c, Electrode placements in the LA and MGm/PIN in vehicle controls (black squares) and U0126-treated rats (white triangles). d, Effects of intrathalamic infusion of 50% DMSO vehicle and U0126 on baseline synaptic transmission in the LA. e, Effects of intrathalamic infusion of 50% DMSO vehicle (black circles) and U0126 (white triangles) on LTP in the LA. Data are expressed as percentage change (relative to baseline) in the amplitude of the field-evoked response in the LA over the 3 h recording period. Representative traces for vehicle and U0126-treated rats before and after LTP are presented in the inset.
Figure 6.
Figure 6.
Effects of intrathalamic infusion of U0126 on auditory-evoked potentials in the MGm/PIN. a, An auditory-evoked field potential in the MGm/PIN (top), averaged over many presentations of a 5 kHz, 50 ms tone pip. Note the initial positive-going (P1) and negative-going (N1) components of the field potential that correspond to the emergence of spiking in the multiunit recording (bottom). b, Effect of intrathalamic infusion of U0126 (1 μg) or 50% DMSO vehicle on P1 and N1 components of the auditory-evoked field potential in the MGm/PIN. c, Representative auditory-evoked field potentials in the MGm/PIN before and after infusion in both vehicle and U0126-treated animals. d, Electrode placements in the MGm/PIN in both vehicle controls (black squares) and animals infused with U0126 (white triangles).

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