Synaptic plasticity in the basolateral amygdala in transgenic mice expressing dominant-negative cAMP response element-binding protein (CREB) in forebrain

G. Rammes, T. Steckler, A. Kresse, G. Schütz, W. Zieglgänsberger, B. Lutz

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93 Scopus citations

Abstract

Electrophysiological and behavioural experiments were performed in transgenic mice expressing a dominant-negative form of cAMP response element-binding protein (CREB(A133)) in the limbic system. In control littermate in vitro slice preparation, tetanizing the lateral amygdala-basolateral amygdala (BLA) pathway with a single train (100 Hz for 1 s) produced short-term potentiation (STP) in the BLA. Five trains (10-8 interstimulus interval) induced long-term potentiation (LTP), which was completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 μM). When GABAergic (γ-aminobutyric acid) inhibition was blocked by picrotoxin (10 μM), LTP became more pronounced. Low-frequency stimulation (1 Hz for 15 min) induced either long-term depression (LTD) or depotentiation. LTD remained unaffected by AP5 (50 μM) or by the L- and T-type Ca2+-channel blockers nifedipine (20 μM) and Ni2+ (50 μM), but was prevented by picrotoxin (10 μM), indicating a GABAergic link in the expression of LTD in the BLA. When conditioned fear was tested, a mild impairment was seen in one of three transgenic lines only. Although high levels of mRNA encoding CREB(A133) lead to downregulation of endogenous CREB, expression of LTP and depotentiation were unaltered in BLA of these transgenic animals. These results could suggest that residual CREB activity was still present or that CREB per se is dispensable. Alternatively, other CRES-like proteins were able to compensate for impaired CREB function.

Original languageEnglish
Pages (from-to)2534-2546
Number of pages13
JournalEuropean Journal of Neuroscience
Volume12
Issue number7
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Amygdala
  • Long-term depression
  • Long-term potentiation
  • Transgenic mice

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