Pharmacological and anatomical analysis of fear conditioning.

The potentiated startle paradigm 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 shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety, since it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Lesion and electrical stimulation studies on fear-potentiated startle and startle increased by electrical stimulation of the amygdala are being used to define the neural pathways necessary for a visual conditioned stimulus to alter the acoustic startle reflex. The current working hypothesis is that the conditioned stimulus activates the central nucleus of the amygdala through a pathway involving the lateral geniculate nucleus and insular cortex. The central nucleus of the amygdala may then project directly to the acoustic startle pathway, modulating the startle response. More work has to be done to define conclusively the relevant neural pathways involved in fear-potentiated startle. Nonetheless, by combining behavioral, anatomical, physiological, and pharmacological approaches, it will be possible to determine each step along the pathway that mediates the ability of a stimulus signaling fear to alter behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways to affect behavior. Eventually, this approach should help to determine where plastic changes take place along these pathways to mediate the conditioned effects that are being measured and the biochemical processes that are involved.