Abstract-1
Pavlovian-to-instrumental transfer (PIT) is a key concept in developing our understanding of cue-controlled behaviours. Here we have reviewed the literature on behavioural and neurobiological factors that influence PIT. Meta-analyses of the data for individual groups in PIT studies revealed that PIT is related to both the order and amounts of instrumental and Pavlovian training, and that it is critically determined by competition between instrumental and Pavlovian responses. We directly addressed the role of response competition in PIT in two experiments which showed that extensive Pavlovian conditioning produced more Pavlovian magazine visits and weaker PIT than moderate Pavlovian conditioning (Experiment 1); and that PIT lost after extensive Pavlovian conditioning was restored by Pavlovian extinction training (Experiment 2). These findings confirm that response competition is indeed an important determinant of PIT. This has significant implications for lesion and inactivation studies that assess the neurobiological substrates of PIT, as well as attempts to demonstrate PIT in the drug self-administration paradigm where the effect is yet to be reliably shown.
Nathan M. Holmes, Alain R. Marchand , Etienne Coutureau . Pavlovian to instrumental transfer: A neurobehavioural perspective. Neuroscience & Biobehavioral Reviews.2010-7.[LINK]
Abstract-2
Dopamine D2 receptors (D2Rs) in the nucleus accumbens (NAc) regulate motivated behavior, but the underlying neurobiological mechanisms remain unresolved. Here, we show that selective upregulation of D2Rs in the indirect pathway of the adult NAc enhances the willingness to work for food. Mechanistic studies in brain slices reveal that D2R upregulation attenuates inhibitory transmission at two main output projections of the indirect pathway, the classical long-range projections to the ventral pallidum (VP), as well as local collaterals to direct pathway medium spiny neurons. In vivo physiology confirms the reduction in indirect pathway inhibitory transmission to the VP, and inhibition of indirect pathway terminals to VP is sufficient to enhance motivation. In contrast, D2R upregulation in the indirect pathway does not disinhibit neuronal activity of the direct pathway in vivo. These data suggest that D2Rs in ventral striatal projection neurons promote motivation by weakening the canonical output to the ventral pallidum.
Eduardo F. Gallo, Jozsef Meszaros, Jeremy D. Sherman, Muhammad O. Chohan, Eric Teboul, Claire S. Choi, Holly Moore, Jonathan A. Javitch & Christoph Kellendonk. Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum. Nature Communications.2018-3.[LINK]
Abstract-3
It was first posited, more than five decades ago, that the etiology of schizophrenia involves overstimulation of dopamine receptors. Since then, advanced clinical research methods, including brain imaging, have refined our understanding of the relationship between striatal dopamine and clinical phenotypes as well as disease trajectory. These studies point to striatal dopamine D2 receptors, the main target for all current antipsychotic medications, as being involved in both positive and negative symptoms. Simultaneously, animal models have been central to investigating causal relationships between striatal dopamine D2 receptors and behavioral phenotypes relevant to schizophrenia. We begin this article by reviewing the circuit, cell-type and subcellular locations of dopamine D2 receptors and their downstream signaling pathways. We then summarize results from several mouse models in which D2 receptor levels were altered in various brain regions, cell-types and developmental periods. Behavioral, electrophysiological and anatomical consequences of these D2 receptor perturbations are reviewed with a selective focus on striatal circuit function and alterations in motivated behavior, a core negative symptom of schizophrenia. These studies show that D2 receptors serve distinct physiological roles in different cell types and at different developmental time points, regulating motivated behaviors in sometimes opposing ways. We conclude by considering the clinical implications of this complex regulation of striatal circuit function by D2 receptors.
Eleanor H. Simpson, Eduardo F. Gallo, Peter D. Balsam, Jonathan A. Javitch & Christoph Kellendonk. How changes in dopamine D2 receptor levels alter striatal circuit function and motivation. Molecular Psychiatry.2021-8.[LINK]
Speaker: Yingjun Tang
Time: 9:00 am, 2023/11/06
Location: CIBR A328
