Distinct Regions of the Periaqueductal Gray Are Involved in the Acquisition and Expression of Defensive Responses

Abstract

In fear conditioning, a rat is placed in a distinct environment and delivered footshock. The response to the footshock itself is called an activity burst and includes running, jumping, and vocalization. The fear conditioned to the distinct environment by the footshock elicits complete immobility termed freezing. Lesions of the ventral periaqueductal gray (vPAG) strongly attenuate freezing. However, lesions of the dorsolateral periaqueductal gray (dlPAG) increase the amount of freezing seen to conditional fear cues acquired under conditions in which intact rats do not demonstrate much fear conditioning. To examine the necessity of these regions in the acquisition and expression of fear, we performed five experiments that examined the effects of electrolytic lesions of the dlPAG and the vPAG in learned and unlearned fear. In experiment 1, lesions of the vPAG strongly attenuated, whereas lesions of the dlPAG enhanced, unconditional freezing to a cat. In experiment 2, lesions of the dlPAG made before but not after training enhanced the amount of freezing shown to conditional fear cues acquired via immediate footshock delivery. In experiment 3, vPAG lesions made either before or after training with footshock decreased the level of freezing to conditional fear cues. Neither dlPAG lesions nor vPAG lesions affected footshock sensitivity (experiment 4) or consumption on a conditioned taste aversion test that does not elicit antipredator responses (experiment 5). On the basis of these results, it is proposed that activation of the dlPAG produces inhibition of the vPAG and forebrain structures involved with defense. In contrast, the vPAG seems to be necessary for postencounter freezing defensive behavior.

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

“…A role for the PAG in mediating fear and anxiety has also been well documented (Bandler and Shipley, 1994;Blanchard et al, 1981;DeOca et al, 1998) and SP neurotransmission has been implicated here as well (De Araujo et al, 1999;Gregg and Siegel, 2003;Mongeau et al, 1998). The findings of our study support a critical role of SP neurotransmission within the PAG in fear-potentiated startle and indicate more specifically that these effects may be mediated primarily by SP receptors in the rostral dlPAG.…”

Deficits in memory and motor performance in synaptotagmin IV mutant mice

“…Additionally, these mutants perform normally in the immediate STFP task, a hippocampal-independent task. Because the mechanisms for production of the freezing response for contextual and cued fear conditioning are similar (43,47,48), it is unlikely that Syt IV mutants exhibited deficits in freezing per se. For example, after context overtraining, Syt IV mutants exhibited freezing comparable to that of wild-type animals (Fig.…”

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

“…It has all the anatomical connectivities one would expect of a major emotion system integrator [7,15,27,61] and it exhibits functional changes as a result of emotional arousal [1,4,6,36]. Electrical and chemical stimulation of the PAG produces defensive and freezing behaviors in the rat [3,30] and many studies have shown that distinct regions of the PAG are involved in the acquisition and expression of various defensive behaviors [19,34]. Dramatic increases in transcriptional activity in the PAG during dominant/submissive encounters have been observed.…”