What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

What ethologically based models have taught us about the neural systems underlying fear and anxiety.

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

The role of the superior colliculus in predatory hunting.

Combining the results of behavioral, neuronal immediate early gene activation, lesion and neuroanatomical experiments, we have presently investigated the role of the superior colliculus (SC) in predatory hunting. First, we have shown that insect hunting is associated with a characteristic large increase in Fos expression in the lateral part of the intermediate gray layer of the SC (SCig). Next, we have shown that animals with bilateral NMDA lesions of the lateral parts of the SC presented a significant delay in starting to chase the prey and longer periods engaged in other activities than predatory hunting. They also showed a clear deficit to orient themselves toward the moving prey and lost the stereotyped sequence of actions seen for capturing, holding and killing the prey. Our Phaseolus vulgaris-leucoagglutinin analysis revealed that the lateral SCig, besides providing the well-documented descending crossed pathway to premotor sites in brainstem and spinal cord, projects to a number of midbrain and diencephalic sites likely to influence key functions in the context of the predatory behavior, such as general levels of arousal, motivational level to hunt or forage, behavioral planning, appropriate selection of the basal ganglia motor plan to hunt, and motor output of the primary motor cortex. In contrast to the lateral SC lesions, medial SC lesions produced a small deficit in predatory hunting, and compared to what we have seen for the lateral SCig, the medial SCig has a very limited set of projections to thalamic sites related to the control of motor planning or motor output, and provides conspicuous inputs to brainstem sites involved in organizing a wide range of anti-predatory defensive responses. Overall, the present results served to clarify how the different functional domains in the SC may mediate the decision to pursue and hunt a prey or escape from a predator.

A role for the periaqueductal gray in switching adaptive behavioral responses.

Previous studies suggested a role for the rostral lateral periaqueductal gray (PAG) in the inhibition of maternal behavior induced by low doses of morphine in dams with previous morphine experience. In the present study, we first showed that unilateral NMDA lesions placed in this particular PAG region prevented the morphine-induced inhibition of maternal behavior in previously morphine-sensitized dams. As suggested by previous Fos data on the PAG, predatory hunting appears as a likely candidate to replace maternal behavior in the morphine-treated dams. By testing saline- and morphine-treated dams with live cockroaches only, we have presently shown that morphine challenge increased insect hunting. Moreover, morphine- and saline-treated dams were also observed in an environment containing pups and roaches. Although most of the saline-treated animals displayed active nursing and only occasionally presented insect hunting, all of the morphine-treated animals ignored the pups and avidly pursued and caught the roaches. We next questioned whether the rostral lateral PAG would be involved in this behavioral switch. Our results showed that unilateral lesions of the rostral lateral PAG, but not other parts of the PAG, partially impaired predatory hunting and restored part of the maternal response. Moreover, bilateral lesions of the rostral lateral PAG produced even more dramatic effects in inhibiting insect hunting and restoring maternal behavior. The present findings indisputably show that the rostral lateral PAG influences switching from maternal to hunting behavior in morphine-treated dams, thus supporting a previously unsuspected role for the PAG in selecting adaptive behavioral responses.