All organisms use environmental stimuli to guide their behavior in adaptive ways. One important class of adaptive behaviors involves responding to threats, stimuli that cause or predict harm. The overall goal of this project is to address some fundamental issues about the neural circuitry through which learned stimuli trigger responses to dangerous or threatening stimuli. To study this these investigators will use behavioral, physiological and anatomical approaches to understand how neutral stimulus that has acquired threat-arousing properties is processed in the amygdala, which is known to be crucially involved in responding to threats. A major controversy has been whether a fearful (threat-arousing) stimulus must enter the amygdala via the lateral nucleus, as much research has suggested, or whether it may also enter the amygdala via the central nucleus. These are called the serial and parallel models of the amygdala, respectively. The studies proposed will test which model is most viable. This project predicts that the serial model is correct. This work will expand our understanding of how organisms adapt to dangerous environmental conditions and the results will also further our understanding of the circuits underlying the learning and memory storage of emotional information. The project will offer the opportunity for training postdoctoral, doctoral, and undergraduate students in basic approaches to the neuroscience of emotion, learning, and memory.
In recent years, there has been a significant rise in research on the amygdala and a commensurate, if not greater, increase in public awareness of this brain region and its role in emotion, memory, and psychiatric disease. With so much interest in this part of the brain, and with the implications of the work being potentially very important to our well-being, it is important that the scientific conclusions be as accurate as possible and that the conclusions be disseminated to the public in a way that is informative. Too often the public version is simplified to the point of being inaccurate. For example, it is common for the public to think that the amygdala is the brain’s fear center. But this is wrong. The amygdala detects and responds to threats but is not the well-spring of the conscious feeling of fear. Another common simplification, one that occurs not only communication with the public but also in scientific discussions, is to generalize findings from one context to another. For example, research on how neural basis of amygdala processing of stimuli that predict appetitive rewards (food, addictive drugs) have been assumed by some to also apply to the processing of stimuli that predict aversive stimuli (shocks). The work done on this grant was aimed at examining whether the appetitive circuitry does in fact apply to aversive processing. The appetitive literature has suggested that the amygdala can be divided into two independent or parallel processing streams: one involving the basolateral group (lateral and basal nuclei) and the other involving the central nucleus. But the aversive literature has suggested that the amygdala is wired in a serial fashion where inputs come into the lateral nucleus and are then sent to the basal and central nucleus. One difference between the appetitive and aversive literature is the behavioral task used. The aversive studies have used Pavlovian conditioning where a tone that predicts a shock comes to elicit freezing behavior in rats. Many of the appetitive studies used a task called Pavlovian to instrumental transfer (PIT). In this task, a stimulus is paired with food through Pavlovian conditioning, and then the Pavlovian stimulus is presented while rats perform a separately trained instrumental task such as bar pressing for food. We therefore developed two PIT tasks. In one, a tone paired with shock was presented while rats shuttled back and forth in a runway to avoid shock. The tone increased shuttling. In the other, the tone was presented while the rats licked to obtain sucrose. The tone suppressed licking. In both of these aversive PIT tasks, we found that the lateral and central nuclei were both important, consistent with the serial rather than parallel interpretation. While this work has so far focused on the neural circuits involved, the next phase of the research begins to explore the cellular and molecular mechanisms that make possible the learning and performance of these responses. We hope that this work will increase awareness amongst scientists that appetitive and aversive processing are different processes in the brain with different circuitry. This work also provides a teaching moment for lay understanding of the amygdala. The results are readily interpreted in terms of cellular mechanisms within specific circuits and do not require mental state terms like fear or emotion to understand how these circuits function. This does not mean that fear or other emotions are epiphenomena. Instead it means that we should not confuse ancient circuits that control conserved behavioral functions with circuits that can allow us to be consciously aware of our inner and outer worlds.
