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

Electrophysiological and behavioural experiments were performed in transgen ic mice expressing a dominant-negative form of cAMP response element-bindin g protein (CREBA133) in the limbic system. In control littermate in vitro s lice preparation, tetanizing the lateral amygdala-basolateral amygdala (BLA ) pathway with a single train (100 Hz for 1 s) produced short-term potentia tion (STP) in the BLA. Five trains (10-s interstimulus interval) induced lo ng-term potentiation (LTP), which was completely blocked by the N-methyl-d- aspartate (NMDA) receptor antagonist d(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 mu m). When GABAergic (gamma-aminobutyric acid) inhibition was bl ocked by picrotoxin (10 mu m), LTP became more pronounced. Low-frequency st imulation (1 Hz for 15 min) induced either long-term depression (LTD) or de potentiation. LTD remained unaffected by AP5 (50 mu m) or by the L- and T-t ype Ca2+-channel blockers nifedipine (20 mu m) and Ni2+ (50 mu m), but was prevented by picrotoxin (10 mu m), indicating a GABAergic link in the expre ssion of LTD in the BLA. When conditioned fear was tested, a mild impairmen t was seen in one of three transgenic lines only. Although high levels of m RNA encoding CREBA133 lead to downregulation of endogenous CREB, expression of LTP and depotentiation were unaltered in BLA of these transgenic animal s. These results could suggest that residual CREB activity was still presen t or that CREB per se is dispensable. Alternatively, other CREB-like protei ns were able to compensate for impaired CREB function.