What the Amygdala Does and Doesn't Do in Aversive Learning

Whether you are a rat or a rabbit or a mouse or a monkey, your brain is constantly learning. Indeed, one could argue that this is one of the primary purposes of the nervous system: to adapt behavior to changing environments by storing a record of experience. When experiences are aversive, the type of learning that encodes memories of such events is generally called ‘aversive learning.’ And although aversive learning is normally adaptive, it occasionally goes awry and contributes to the pathology associated with clinical disorders of fear and anxiety, such as posttraumatic stress disorder. As such, there is an urgent need to understand the behavioral principles and brain mechanisms of aversive learning. In recent years, an impressive body of literature has implicated the amygdala, a collection of nuclei buried deep within the temporal lobe, in aversive learning (McGaugh 1989; Davis 1992; LeDoux 2000; Calder et al. 2001; Davis and Whalen 2001; Maren 2001). Notably, the amygdala is critical for Pavlovian fear conditioning, a form of classical conditioning in which animals learn relationships between aversive events and the stimuli that predict them. In particular, numerous studies indicate that either neurotoxic lesions or pharmacological inactivation of the basolateral amygdaloid complex (BLA; comprised of the lateral, basolateral, and basomedial amygdaloid nuclei) disrupts the acquisition and expression of Pavlovian fear memories (Helmstetter and Bellgowan 1994; Campeau and Davis 1995; Maren et al. 1996; Muller et al. 1997; Cousens and Otto 1998). There is only one instance in which rats with BLA lesions exhibit conditional fear responses, and that occurs following extensive overtraining (Maren 1998, 1999). However, a recent report challenges the view that the amygdala is required for learning Pavlovian associations during aversive conditioning. In a recent issue of Learning & Memory, Lehmann et al. (2003) report experiments suggesting that the amygdala is not essential for the learning that occurs when rats are exposed to an electrified shock probe, a procedure they call “shock-probe fear conditioning.” In two experiments those authors infused tetrodotoxin (TTX), which reversibly inhibits neuronal activity, into the BLA prior to shock-probe fear conditioning. They found that TTX infusions into the BLA affected probe avoidance during training, with BLA-treated rats contacting the probe more than five times as often as controls. However, Lehmann and colleagues found that retention of the shock-probe training, which was indexed by measuring the number of contacts the rats made with the probe four days after training, was minimally affected by BLA inactivation. The authors concluded that “... the amygdala is not necessary for the acquisition of the association between the shock and the cue, but is involved in some other process that influences performance” (Lehmann et al. 2003). On the face of it, this conclusion challenges a widely held view that the BLA is importantly involved, if not essential under most circumstances, for the acquisition of stimulus–stimulus associations that underlie long-term memories for Pavlovian fear conditioning. But is the essence of learning and memory in the shockprobe task a Pavlovian association? Lehmann et al. imply that avoidance performance in the shock-probe task is guided by “the association between the shock and the cue” and have labeled this learning “shock-probe fear conditioning.” Because our ability to assign function to brain systems in learning tasks is only as good as our understanding of the psychological processes underlying those tasks, it is essential that we understand the learning mechanisms that govern “shock-probe fear conditioning” before concluding that the amygdala is or isn’t involved. To understand aversive learning, experimental psychologists and behavioral neuroscientists have developed laboratory paradigms that attempt to distill fundamental psychological processes under experimentally controlled conditions. For example, repeated presentation of an aversive stimulus, such as a loud noise, is used to study nonassociative learning processes including habituation and sensitization. Contingent and response-independent presentations of two different stimuli, such as an innocuous tone and an aversive footshock, is used to study Pavlovian (classical) conditioning. Contingent but response-dependent presentation of a stimulus, such as delivering footshock to an animal when it crosses into a dark compartment, is used to study instrumental (operant) conditioning. One primary goal of neuroscience is to understand the neural mechanisms of these types of learning. And although they may appear simple, at least in a procedural sense, there is more complexity than meets the eye. Aversive learning is not monolithic in either a psychological or neurobiological sense. Many sensory, motivational, and motor processes serve it, and it requires the coordinated operation of many neural systems. The involvement of multiple psychological processes and neural systems in aversive learning is a testament to its complexity and importance. When rats are submitted to “shock-probe fear conditioning,” they are placed in an enclosure containing a wire-wrapped and electrified probe extending from one wall (Fig. 1). During exploration of the enclosure, rats invariably approach the probe and receive a brief electric shock, typically to the nose. After receiving one or more shocks, rats come to avoid the probe and will make many fewer contacts with the electrified probe during later retention tests. In addition, rats will spray bedding or other substrates (if available) at the probe to bury it. Probe burying is thought to be a species-specific defense response emitted to focal aversive stimuli (Pinel and Treit 1978; but see Fanselow et al. 1987). Importantly, both probe avoidance and burying reduce the number of shocks an animal receives, and thereby would be expected to be under the control of instrumental contingencies. Therefore, “shock-probe fear conditioning” involves not only a Pavlovian contingency, but also an instrumental contingency. Pavlovian conditioning of probe-shock and context-shock associations yields conditioned fear responses (such as freezing) to the probe or enclosure, whereas instrumental conditioning of E-MAIL maren@umich.edu; FAX (734) 763-7480. Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/ lm.68403.