title: A GABAergic Projection from the Centromedial Nuclei of the Amygdala to Ventromedial Prefrontal Cortex Modulates Reward Behavior.
abstract: The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-CreCeMA-vmPFC) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice. Pathway-specific optogenetic activation of the VGat-CreCeMA-vmPFCcircuit in awake, behaving animals produced a positive, reward-like phenotype in real-time place preference and increased locomotor activity in open-field testing. In sucrose operant conditioning, the photoactivation of these terminals increased nose-poking effort with no effect on licking behavior and robustly facilitated the extinction of operant behavior. However, photoactivation of these terminals did not induce self-stimulation in the absence of an external reward. The results described here suggest that the VGat-CreCeMA-vmPFCprojection acts to modulate existing reward-related behaviors.
  
  
  
  Many studies have shown that the interactions between the centromedial nucleus of the amygdala (CeMA) and ventromedial PFC (vmPFC) have critical roles for emotional regulation. However, most studies have associated this circuit with fear and anxiety behaviors and emphasized top-down processing from vmPFC to CeMA. Here, we provide new evidence for bottom-up CeMA to vmPFC influence on reward-related behaviors. Although previous work implicated the CeMA in incentive salience, our results isolate the investigation to a specific CeMA GABAergic projection to the vmPFC. This long-range GABAergic interaction between amygdala and frontal cortex adds a new dimension to the complex regulation of reward-related behaviors.
authors: Department of Anesthesiology, Division of Basic Research.
authors: Dong-Oh
authors: 0000-0003-0315-4489
authors: DO
authors: Seo
authors: Department of Anesthesiology, Division of Basic Research.|Diabetes, Endocrinology and Obesity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, and.
authors: Samuel C
authors: 0000-0001-5146-2035
authors: SC
authors: Funderburk
authors: Department of Anesthesiology, Division of Basic Research.
authors: Dionnet L
authors: 0000-0003-3031-2067
authors: DL
authors: Bhatti
authors: Department of Anesthesiology, Division of Basic Research.
authors: Laura E
authors: LE
authors: Motard
authors: Department of Anesthesiology, Division of Basic Research.
authors: Dillan
authors: 0000-0002-5826-3546
authors: D
authors: Newbold
authors: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors: Kasey S
authors: KS
authors: Girven
authors: Department of Anesthesiology, Division of Basic Research.
authors: Jordan G
authors: JG
authors: McCall
authors: Diabetes, Endocrinology and Obesity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, and.
authors: Michael
authors: M
authors: Krashes
authors: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors: Dennis R
authors: DR
authors: Sparta
authors: Department of Anesthesiology, Division of Basic Research, bruchasm@wustl.edu.|Department of Neuroscience, and.|Pain Center, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Michael R
authors: 0000-0003-4713-7816
authors: MR
authors: Bruchas
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D005108:Extinction, Psychological; D008297:Male; D051379:Mice; D009043:Motor Activity; D009434:Neural Pathways / Q000502:physiology; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000502:physiology*; D012201:Reward; D012653:Self Stimulation; D013395:Sucrose / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid; D013395:Sucrose
keywords: CEA; MEA; amygdala; reward; vGat; vmPFC