FEAR-POTENTIATED STARTLE - A NEURAL AND PHARMACOLOGICAL ANALYSIS

The fear-potentiated startle paradigm has proven to be a useful system with which to analyze neural systems involved in fear and anxiety. Th is test measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with a shock. Fear-potentiated startle is sensitive to a variety of drugs such as diazepam, morphine, and buspirone that r educe anxiety in people and can be measured reliably in humans when th e eyeblink component of startle is elicited at a time when they are an ticipating a shock. Electrical stimulation techniques suggest that a v isual conditioned stimulus ultimately alters acoustic startle at a spe cific point along the acoustic startle pathway. The lateral, basolater al and central amygdaloid nuclei and the caudal branch of the ventral amygdalofugal pathway projecting to the brainstem are necessary for po tentiated startle to occur. The central nucleus of the amygdala projec ts directly to one of the brainstem nuclei critical for startle and el ectrical stimulation of this nucleus increases startle amplitude. Chem ical or electrolytic lesions of either the central nucleus or the late ral and basolateral nuclei of the amygdala block the expression of fea r-potentiated startle. The perirhinal cortex, which projects directly to the lateral and basolateral amygdaloid nuclei, plays a critical rol e in the expression of fear-potentiated startle using either visual or auditory conditioned stimuli. These latter amygdaloid nuclei may actu ally be the site of plasticity for fear conditioning, because local in fusion of the NMDA antagonist AP5 into these nuclei blocks the acquisi tion of fear-potentiated startle. On the other hand, the expression of fear-potentiated startle is blocked by local infusion of the non-NMDA ionotropic antagonist CNQX or the G-protein inactivating toxin, pertu ssis toxin, but not by AP5. Finally, we have begun to investigate brai n systems that might be involved in the inhibition of fear. Local infu sion of AP5 into the amygdala was found to block the acquisition of ex perimental extinction, a prototypical method for reducing fear. We hav e also established a reliable procedure for producing both external an d conditioned inhibition of fear-potentiated startle and hope to event ually understand the neural systems involved in these phenomena.