title: Hippocampus and Prefrontal Cortex Predict Distinct Timescales of Activation in the Human Ventral Tegmental Area.
abstract: The mesolimbic dopamine system contributes to a remarkable variety of behaviors at multiple timescales. Midbrain neurons have fast and slow signaling components, and specific afferent systems, such as the hippocampus (HPC) and prefrontal cortex (PFC), have been demonstrated to drive these components in anesthetized animals. Whether these interactions exist during behavior, however, is unknown. To address this question, we developed a novel analysis of human functional magnetic resonance imaging data that fits models of network excitation and inhibition on ventral tegmental area (VTA) activation. We show that specific afferent systems predict distinct temporal components of midbrain VTA signal. We found that PFC, but not HPC, positively predicted transient, event-evoked VTA activation. In contrast, HPC, but not PFC, positively predicted slow shifts in VTA baseline variability. Thus, unique functional contributions of afferent systems to VTA physiology are detectable at the network level in behaving humans. The findings support models of dopamine function in which dissociable neural circuits support different aspects of motivated behavior via active regulation of tonic and phasic signals.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Vishnu P
authors.initials: VP
authors.lastname: Murty
authors.affiliation: Stanford Neurosciences Graduate Training Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Ballard
authors.affiliation: Center for Cognitive Neuroscience.|Department of Psychiatry and Behavioral Sciences.|Department of Psychology and Neuroscience.|Department of Neurobiology, Duke University, Durham, NC 27708, USA.
authors.forename: R Alison
authors.initials: RA
authors.lastname: Adcock
mesh_terms: D000328:Adult; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology*; D055815:Young Adult
chemical_list: D004298:Dopamine
keywords: VTA; baseline; hippocampus; network connectivity; prefrontal cortex
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