Neuronal circuits of fear memory and fear extinction

Abstract

The paradigm“eat or be eaten” has proven to be a critical guiding element during the evolution of both humans and animals. This helps to explain the fact that the ability to de­tect danger or a threat has been highly con­served throughout evolution and thus exhib­its a high degree of homology between spe­cies. Studies in laboratory animals thereby enable the identification of key neurochem­ical, cellular and molecular mechanisms un­derlying fear and anxiety, and important­ly, permit conclusions to be drawn regard­ing the situation in humans. This, in turn, pro­vides a highly valuable basis for further im­provements in prognosis, diagnosis, preven­tion and therapy of anxiety disorders. The present article focuses on one aspect cen­tral to translational anxiety research: the neu­ronal substrates and circuits of fear memo­ry and fear extinction. Following a brief intro­duction into the principles of fear condition­ing, the synaptic circuits that underlie the ac­quisition and extinction of fear memories in the mammalian brain will be described. His­torically established principles will be system­atically compared with novel findings on the detailed synaptic circuitry of the fear matrix. Knowledge of the neuronal substrates and circuitry will significantly improve our under­standing of pathologically transformed states of fear and anxiety and thereby help to derive novel intervention strategies for the treat­ment of anxiety disorders.