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Decades of research have identified a role for dopamine neurotransmission in prefrontal cortical function and flexible cognition. Abnormal dopamine neurotransmission underlies many cases of cognitive dysfunction. New techniques using optogenetics have allowed for ever more precise functional segregation of areas within the prefrontal cortex, which underlie separate cognitive functions. Learning theory predictions have provided a very useful framework for interpreting the neural activity of dopamine neurons, yet even dopamine neurons present a range of responses, from salience to prediction error signaling. The functions of areas like the Lateral Habenula have been recently described, and its role, presumed to be substantial, is largely unknown. Many other neural systems interact with the dopamine system, like cortical GABAergic interneurons, making it critical to understand those systems and their interactions with dopamine in order to fully appreciate dopamine's role in flexible behavior. Advances in human clinical research, like exome sequencing, are driving experimental hypotheses which will lead to fruitful new research directions, but how do (or should?) these clinical findings inform basic research? Following new information from these techniques, we may begin to develop a fresh understanding of human disease states which will inform novel treatment possibilities. However, we need an operational framework with which to interpret these new findings. Therefore, the purpose of this Research Topic is to integrate what we know of dopamine, the prefrontal cortex and flexible behavior into a clear framework, which will illuminate clear, testable directions for future research.

behavioral flexibility --- Dopamine --- medial prefrontal cortex (mPFC) --- Attentional set-shifting --- basal forebrain --- anterior cingulate cortex (ACC) --- endocannabinoid system --- lateral habenula (LHb) --- Locus coeruleus (LC) --- motivational salience

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The book “Protective and Detrimental Role of Heme Oxygenase-1”, includes a selection of original research papers and reviews aimed at understanding the dual role (protective and detrimental) of HO-1 and the involved signaling pathways. Original research papers and reviews aimed at the identification of natural molecules or new synthetic compounds able to modulate HO-1 activity/expression help make HO-1 a potential therapeutic target for the amelioration of various diseases.

coronary artery disease --- n/a --- glucocorticoid receptor --- antigen presentation --- analgesia --- chemotherapy --- locus coeruleus --- Sirtuin 1 --- thiol groups --- Heme Oxygenase-1 --- Betula etnensis Raf. --- heme oxygenase 1 --- tolerance --- heme oxygenase --- atherosclerosis --- nitric oxide --- caloric restriction --- liver --- carbon monoxide --- ER stress --- heme oxygenase-1 --- mineralocorticoid receptor --- Type 1 diabetes mellitus (T1D) --- Gamma-Glutamyl-Cysteine Ligase (GGCL) --- angiotensin II --- bilirubin --- Heme oxygenase-1 (HO-1) inducers --- Inducible nitric oxide synthase (iNOS) --- HO-1 activity inhibitor --- ferroptosis --- Myristica fragrans kernels --- glutathione --- high-pressure gas --- apoptosis --- HO-1 --- diabetes mellitus --- Caffeic acid phenethyl ester (CAPE) --- carotid plaque --- ischemia–reperfusion injury --- ANTIGEN presenting cell --- LPS --- endoplasmic reticulum stress --- hemoglobin --- Pancreatic oxidative damage --- Colon cancer --- inflammation --- reactive oxygen species --- inflammatory pain --- paracetamol --- cardiomyopathy --- heme oxigenase-1 --- adipocytes --- sirtuin 1 --- peripheral artery disease --- PGC-1? --- heme --- Reactive oxygen species (ROS) --- metformin --- GR --- prostate cancer --- NF-?B --- hyperbilirubinemia --- iron --- Tet-ON system --- lung preservation --- oxidative stress --- Gunn rats --- Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) --- ischemia-reperfusion injury