Role of Ventrolateral Periaqueductal Gray Neurons in the Behavioral and Cardiovascular Responses to Contextual Conditioned Fear and Poststress Recovery

We have previously shown that conditioned fear to context increases Fos expression in the caudal ventrolateral region of the periaqueductal gray in the rat. To understand the reason for this activation and its role in the expression of the contextual fear response, the ventrolateral periaqueductal gray was temporarily blocked with bilateral microinjections (0.4 microl) of the GABA agonist muscimol (0.2 mM) or the glutamate antagonist kynurenic acid (0.1 M). Cardiovascular changes and activity were recorded by radio-telemetry and the microinjections were made immediately before testing the conditioned response in the aversive context. Muscimol and kynurenic acid had the same effects: when compared to saline controls, freezing immobility and ultrasonic vocalizations were reduced and replaced by marked locomotor activity, and the increase in heart rate was enhanced; however, the increase in arterial blood pressure remained the same. Interesting changes were also observed when animals were returned to the safe context of their home box after fear (recovery). Basically, the recovery response was either prevented or delayed: instead of returning to resting immobility, the rats remained agitated in their home box with a moderately elevated activity, heart rate and blood pressure. However, the effect of ventrolateral periaqueductal gray blockade on heart rate, arterial pressure and activity did not appear to be specific to the fear response or its recovery because they were also observed in animals returned to the safe context of their home box immediately after injection. The later response was also a recovery response from the milder stress of handling and the injection procedure.We discuss the results by arguing that the ventrolateral periaqueductal gray is involved in the immobility component of both the fear response and poststress recovery responses. To explain our interpretation we consider the findings in relation to the classic descending defence-arousal system and the hyporeactive-hypotensive immobility pattern that has been attributed to the ventrolateral periaqueductal gray. We propose that there is a dual activation of the defence-arousal system and of the ventrolateral periaqueductal gray during fear, with the ventrolateral periaqueductal gray acting as a brake on the defence-arousal system. The role of this brake is to impose immobility and hold off active defence responses such as fight and flight. The result of this combination of arousal and immobility is a hyperreactive freezing immobility associated with ultrasonic vocalizations, and a pressor response accompanied with a slow rise in heart rate. Basically, the animal is tense and ready for action but temporarily immobilised. The ventrolateral periaqueductal gray also acts to impose immobility during recovery; however, this is without coactivation of the defence-arousal system. The result is a return to resting immobility, associated with a return to baseline blood pressure and heart rate. This is an active process that insures a faster and complete return to rest. We conclude that the ventrolateral periaqueductal gray is an immobility center involved not only in the fear response but also in poststress recovery responses.