Dorsolateral and ventral regions of the periaqueductal gray matter are involved in distinct types of fear.

Stepwise increases in the electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) produces alertness, then freezing and finally escape. This paper examines whether this freezing is (i) caused by Pavlovian fear conditioning to the contextual cues present during stimulation and (ii) the result of the stimulation of neurons located inside the dlPAG or elsewhere. To this end, freezing behavior was assessed in rats exposed either to the same or a different environment (context shift test) following the application of either footshocks or stimulation of the dlPAG at the freezing threshold. Rats submitted to footshocks presented freezing to the context 24h later whereas rats submitted to the dlPAG stimulation showed freezing only immediately after the stimulation, regardless of the context. In the second experiment, aversive states generated by activation of the dlPAG were assessed either by measuring the thresholds for freezing and escape responses or the duration of these responses following microinjections of semicarbazide inside the dlPAG. The duration of freezing behavior was also measured in rats submitted to a contextual fear-conditioning paradigm using footshocks as unconditioned stimulus. Lesions of the ventral periaqueductal gray (vPAG) disrupted conditioned freezing to contextual cues associated to footshocks but vPAG lesions did not change the threshold of either freezing or escape responses elicited by electrical stimulation of the dlPAG. Lesions of the vPAG did not change the amount of freezing or escape responses produced by microinjections of semicarbazide into the dlPAG. These results indicate that stimulation of dlPAG neurons produce freezing behavior independent of any contextual fear conditioning and add to previously reported evidence showing that the vPAG is a critical structure for the expression of conditioned fear. In contrast, the neural substrate of unconditioned dlPAG stimulation-induced freezing is likely to elaborate unconditioned fear responses to impending danger, which have been implicated in panic disorder.