Phasic increases and decreases in dopamine (DA) transmission encode reward prediction errors thought to facilitate reward-related learning, yet how these signals guide action selection in more complex situations requiring evaluation of different reward remains unclear. We manipulated phasic DA signals while rats performed a risk/reward decision-making task, using temporally discrete stimulation of either the lateral habenula (LHb) or rostromedial tegmental nucleus (RMTg) to suppress DA bursts (confirmed with neurophysiological studies) or the ventral tegmental area (VTA) to override phasic dips. When rats chose between small/certain and larger/risky rewards, LHb or RMTg stimulation, time-locked to delivery of one of these rewards, redirected bias toward the alternative option, whereas VTA stimulation after non rewarded choices increased risky choice. LHb stimulation prior to choices shifted bias away from more preferred options. Thus, phasic DA signals provide feedback on whether recent actions were rewarded to update decision policies and direct actions toward more desirable reward.
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http://dx.doi.org/10.1016/j.neuron.2014.08.033 | DOI Listing |
ACS Nano
December 2024
Faculty of Materials Science, Shenzhen MSU-BIT University, Shenzhen 518100, P. R. China.
Protein hydrolysis targeted chimeras (PROTACs) represent a different therapeutic approach, particularly relevant for overcoming challenges associated with traditional small molecule inhibitors. These challenges include targeting difficult proteins that are often deemed "undruggable" and addressing issues of acquired resistance. PROTACs employ the body's own E3 ubiquitin ligases to induce the degradation of specific proteins of interest (POIs) through the ubiquitin-proteasome pathway.
View Article and Find Full Text PDFMalays J Pathol
December 2024
Universiti Sains Malaysia, School of Dental Sciences, Health Campus, Kubang Kerian, Kelantan, Malaysia.
Introduction: Oral cancer is considered the sixth most common form of cancer worldwide. It causes significant morbidity and mortality, especially in low socioeconomic status groups. However, Cancer chemoprevention encompasses the use of specific compounds to suppress the growth of tumours or inhibit carcinogenesis.
View Article and Find Full Text PDFNeuro Oncol
December 2024
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor's lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor's action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.
View Article and Find Full Text PDFSci Rep
December 2024
Computational Systems Biomedicine Lab, Institut Pasteur, Université Paris Cité, Paris, France.
Personalized medicine aims to tailor medical treatments to individual patients, and predicting drug responses from molecular profiles using machine learning is crucial for this goal. However, the high dimensionality of the molecular profiles compared to the limited number of samples presents significant challenges. Knowledge-based feature selection methods are particularly suitable for drug response prediction, as they leverage biological insights to reduce dimensionality and improve model interpretability.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S.
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