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

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

94 Zitate (Scopus)

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.

OriginalspracheEnglisch
Seiten (von - bis)2534-2546
Seitenumfang13
FachzeitschriftEuropean Journal of Neuroscience
Jahrgang12
Ausgabenummer7
DOIs
PublikationsstatusVeröffentlicht - 2000
Extern publiziertJa

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