A hallmark of various psychiatric disorders is biased future predictions. Here we examined the mechanisms for biased value learning using reinforcement learning models incorporating recent findings on synaptic plasticity and opponent circuit mechanisms in the basal ganglia. We show that variations in tonic dopamine can alter the balance between learning from positive and negative reward prediction errors, leading to biased value predictions. This bias arises from the sigmoidal shapes of the dose-occupancy curves and distinct affinities of D1- and D2-type dopamine receptors: changes in tonic dopamine differentially alters the slope of the dose-occupancy curves of these receptors, thus sensitivities, at baseline dopamine concentrations. We show that this mechanism can explain biased value learning in both mice and humans and may also contribute to symptoms observed in psychiatric disorders. Our model provides a foundation for understanding the basal ganglia circuit and underscores the significance of tonic dopamine in modulating learning processes.
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http://dx.doi.org/10.1101/2023.11.10.566580 | DOI Listing |
bioRxiv
January 2025
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston MA 02115.
The concentrations of extracellular and intracellular signaling molecules, such as dopamine and cAMP, change over both fast and slow timescales and impact downstream pathways in a cell-type specific manner. Fluorescence sensors currently used to monitor such signals are typically optimized to detect fast, relative changes in concentration of the target molecule. They are less well suited to detect slowly-changing signals and rarely provide absolute measurements of either fast and slow signaling components.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Departments of Psychiatry and Neurology, Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York 10032, United States.
Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons, which extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs. acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than recordings.
View Article and Find Full Text PDFScience
January 2025
Department of Neurology, the First Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTA) neurons.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
State Key Laboratory of Membrane Biology, National Biomedical Imaging Center and Institute of Molecular Medicine, College of Future Technology, Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown.
View Article and Find Full Text PDFJ Neurophysiol
February 2025
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States.
The thalamic reticular nucleus (TRN) is a thin shell of gap junction-coupled GABAergic inhibitory neurons that regulate afferent sensory relay of the thalamus. The TRN receives dopaminergic innervation from the midbrain, and it is known to express high concentrations of D1 and D4 receptors. Although dopaminergic modulation of presynaptic inputs to TRN has been described, the direct effect of dopamine on TRN neurons and its electrical synapses is largely unknown.
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