VTA-forebrain connectivity moderates adaptive behavior

Neural representation of the environment is pertinent for adaptive behaviors. Such neural maps are processed in the hippocampus and contain information about spatial locations, novelties, context, and cues for context discrimination. In conjunction with other subcortical structures, a key function of the hippocampus is to compare newly detected novelties derived from the environment with previously stored cortical memories. These neural events underscore the role of the hippocampus as a “comparator” and “hub” for sorting novelties to determine priority and weight assignments for long-term cortical storage. To propagate these cognitive processes, mesocorticolimbic ventral tegmental area (VTA) inputs to the hippocampus and prefrontal cortex (PFC) compute detected novelties to derive frameworks for context discrimination, valence designation, and experience-based learning. Additionally, reciprocal connections between the VTA-hippocampus and VTA-PFC circuits are engaged for guided decisions and expression of adaptive behaviors. The significance of the functionally linked VTA-hippocampus and VTA-PFC axis in learning and guided decision-making has been generally described within the GO-STOP framework, which involves the coordinated activation or inhibition of ensembles in the prelimbic (PrL) and infralimbic (IL) cortices, among others. Although the GO-STOP hypothesis has been excellently described in recent works, this review evaluates the functional continuum between the VTA-hippocampus loop and VTA regulation of cortical-linked executive cognitive processes which underscore the expression of adaptive behaviors, with associated implications in psychological and neurodevelopmental disorders.