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.
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.
Apergis-Schoute
Annemieke M
AM
W. M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA.
Debiec
Jacek
J
Doyère
Valérie
V
LeDoux
Joseph E
JE
Schafe
Glenn E
GE
D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009473:Neuronal Plasticity; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology; D013788:Thalamus / Q000502:physiology*
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126