Fear-potentiated startle, but not prepulse inhibition of startle, is impaired in CREBαΔ-/- mutant mice

Fear-potentiated startle was assessed in mice with a targeted disruption of the alpha and delta isoforms of the transcription factor cAMP response element binding protein (CREB) 24 hr after 5 tone + shock training trials. Whereas wild-type mice showed fear-potentiated startle that persisted up to 45 days after training, CREB" mice failed to show fear-potentiated startle. However, CREB° and wild-type mice had similar startle amplitudes and similar magnitudes of prepulse inhibition of startle, suggesting that CREB 04 "'" mice have no obvious sensory or motor deficits. These results add to the literature indicating that CREB-activated transcription plays a critical role in the formation of long-term memory and illustrate the utility of the fear-potentiated startle paradigm for assessing cognition in genetically altered mice. A considerable number of studies have implicated the transcription factor cAMP response element binding protein (CREB) in the formation of long-term memory (Abel & Kandel, 1998; Silva, Kogan, Frankland, & Kida, 1998; Yin & Tully, 1996). For example, procedures that interfere with CREB activation in cultured Aplysia sensory neurons block long-term synaptic facilitation (Alberini, Ghirardi, Metz, & Kandel, 1994; Dash, Hochner, & Kandel, 1990), and pretraining induction of a dominant negative CREB transgene interferes with long-term olfactory memory in Drosophila (Yin et al., 1994). CREB has also been implicated in mammalian long-term memory processes. Local infusion of oligodeoxynucleotide antisense to CREB into the hippocampus (Guzowski & McGaugh, 1997) or amygdala (Lamprecht, Hazvi, & Dudai, 1997) interferes with long-term memory in rats. Mice with a targeted disruption of the alpha and delta isoforms of CREB show long-term memory deficits in several learning and memory tasks, including Morris water maze (Bourtchuladze et al., 1994; Kogan et al., 1997), social transmission of food preferences (Kogan et al., 1997), social recognition (Kogan, Frankland, &