A single traumatic experience can result in the development of overgeneralized fear, as observed in Posttraumatic Stress Disorder (PTSD). To understand PTSD and related disorders, basic research using animal models has focused on identifying the neural circuits that are responsible for the acquisition and expression of Pavlovian conditioned fear. Clinically, however, a major problem seen in these disorders is an inability to reduce or inhibit the traumatic memories and the associated anxiety. Hence, an important area of inquiry concerns the way unwanted memories can be reduced or inhibited and why this is so difficult following traumatic fear conditioning. There has been very little basic research examining neural circuits responsible for reducing fear. The long term goals of the P.I.'s research are to (1) identify and examine the neural circuits involved in the reduction of fear and (2) assess whether exaggerated fear, as observed in PTSD, can be understood in terms of a disruption in the processes that normally reduce fear. The proposed research will use rats in a conditioned inhibition of fear procedure to identify the neural circuit responsible for the reduction of fear. In this procedure, one stimulus (e.g., a light) acquires the ability to produce fear while another stimulus (e.g., a noise) acquires the ability to reduce fear. Because the neural circuit for conditioned inhibition must be responsive to afferent sensory input provided by the fear reducing stimulus, experiments will identify the auditory structures that process the auditory fear reducing stimulus. Identification of this """"""""sensory limb"""""""" of the conditioned inhibition circuit will provide a starting point for future proposals that will identify other components of the circuit responsible for conditioned inhibition of fear. This project will be the first to systematically evaluate the neural circuits involved in the reduction of fear and will provide the foundation for further examining the brain mechanisms and neurotransmitters involved in the reduction of fear. The results of this work will provide important new information that will further our understanding of PTSD and related disorders and may lead to new and more effective treatments for these disorders.
| Heldt, Scott A; Coover, Gary D; Falls, William A (2002) Posttraining but not pretraining lesions of the hippocampus interfere with feature-negative discrimination of fear-potentiated startle. Hippocampus 12:774-86 |
