The Periaqueductal Gray (PAG)

This issue covers a broad territory of PAG function: neu-ropharmacology, functional organization, and PAG plasticity in adaptive behavior, emotion, anxiety, and the less-studied plasticity of the PAG function in females. Interest in the involvement of PAG in defensive behavior has a long history. Thinking about this area was radically changed by the seminal contributions of Bandler and DePaulis in defining functional columns arranged in both coronal and saggital planes of the PAG. Most papers in this section respect the importance of those functional columns while adding to our understanding how they might contribute to panic, anxiety, defensive response to natural threats, as well as aversive learning. Del-Ben and Graeff in the paper entitled " Panic disorder: Is the PAG involved? " review preclinical as well as human imaging research in the contribution of PAG dysfunction to panic anxiety disorder. Others have shown how preclinical models of posttraumatic stress disorder (PTSD) and using brief exposure to predators (predator stress) have helped to advance our understanding of the neural substrates of stress-induced lasting sensitization of rodent anxiety including potentiation of startle response. Adamec et al. contribution in the paper entitled " Viral Vector Induction of CREB Expression in the Periaqueductal Gray Induces a Predator Stress-Like Pattern of Changes in pCREB Expression, Neuroplasticity and Anxiety in Rodents " extends initial findings implicating pCREB expression in the lateral column of the PAG in neuroplastic changes in amygdala-PAG communication as mediators of predator stress-enhanced startle and anxiety. Using viral vector enhancement of CREB expression in the PAG, the authors provide support for the idea that stress-precipitated increases in pCREB in the PAG are sufficient to potentiate central amygdala to PAG neural transmission, to increase anxiety in the elevated plus maze, and to potentiate startle response. In a related vein, exposure to stressful stimuli increases endocannabinoid (eCB) levels in the PAG and local administration of cannabinoid receptor 1 (CB1) agonists or drugs that facilitate eCB-mediated neurotransmission produce antinociceptive and antiaversive effects. Stimulated by these findings, Moreira et al. in " Anti-aversive effects of cannabinoids: is the periaqueductal gray involved? " explore the anxiolytic potential of PAG injection of CB1 agonists and cannabidiol in a variety of tests of anxiety as well as in contextual fear conditioning. They provide evidence that dorsal lateral PAG is a site of antiaversive actions of cannabinoids. Other PAG columnar function (ventrolateral PAG-VlPAG) in antinociception is explored by Morgan et al. in …