title: Linking context with reward: a functional circuit from hippocampal CA3 to ventral tegmental area.
abstract: Reward-motivated behavior is strongly influenced by the learned significance of contextual stimuli in the environment. However, the neural pathways that mediate context-reward relations are not well understood. We have identified a circuit from area CA3 of dorsal hippocampus to ventral tegmental area (VTA) that uses lateral septum (LS) as a relay. Theta frequency stimulation of CA3 excited VTA dopamine (DA) neurons and inhibited non-DA neurons. DA neuron excitation was likely mediated by disinhibition because local antagonism of γ-aminobutyric acid receptors blocked responses to CA3 stimulation. Inactivating components of the CA3-LS-VTA pathway blocked evoked responses in VTA and also reinstatement of cocaine-seeking by contextual stimuli. This transsynaptic link between hippocampus and VTA appears to be an important substrate by which environmental context regulates goal-directed behavior.
authors.affiliation: Behavioral Neuroscience Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. alice_luo@hotmail.com
authors.forename: Alice H
authors.initials: AH
authors.lastname: Luo
authors.forename: Pouya
authors.initials: P
authors.lastname: Tahsili-Fahadan
authors.forename: Roy A
authors.initials: RA
authors.lastname: Wise
authors.forename: Carl R
authors.initials: CR
authors.lastname: Lupica
authors.forename: Gary
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal; D001931:Brain Mapping; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D003042:Cocaine / Q000008:administration & dosage; D004298:Dopamine / Q000502:physiology; D058999:Drug-Seeking Behavior; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration; D012686:Septal Nuclei / Q000502:physiology*; D013826:Theta Rhythm; D017557:Ventral Tegmental Area / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000502:physiology
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D003042:Cocaine; D004298:Dopamine