This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A single traumatic experience can result in the development of over generalized fear, as observed in Posttraumatic Stress Disorder (PTSD). To understand these disorders, basic research has focused on identifying the neural systems that are responsible for the acquisition of Pavlovian conditioned fear. Clinically, a major problem seen in these disorders is an inability to inhibit the traumatic memories and the associated fear. Hence, an important area of inquiry concerns the way unwanted memories can be reduced or inhibited. Recent advances in molecular and genetic techniques have provided an unprecedented opportunity to examine the molecular basis of fear reduction. Experiments are examining the molecular and genetic basis of extinction and the modulation of extinction of conditioned fear. The modulation of extinction is being examined with renewal and reinstatement procedures in which extinguished fear to a tone is recovered when the tone is presented outside of the extinction context (renewal) or when the tone is subsequently presented in an aversive context (reinstatement).
In Specific Aim 1 we have examined extinction, renewal and reinstatement in C57BL/6 and DBA/2 mice. We have found that following successful extinction, extinction memory is retained for up to 6 weeks. We have found that renewal and reinstatement are absent in DBA2/J mice. We have also found that reinstatement in C57 mice is context specific as it is in rats. Work on Specific Aim 2 has been halted.
In Specific Aim 3 we have examined the contribution of CREB to reinstatement in mice transgenic for an inducible repressor of CREB. We have preliminary evidence that decreasing CREB function by activating the CREB repressor transgene interferes with reinstatement.
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