Spiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release. We show that iSPN plasticity prevents successful learning, as it reinforces activity patterns associated with negative outcomes. However, this pathological behavior is reversed if functionally opponent dSPNs and iSPNs, which promote and suppress the current behavior, are simultaneously activated by efferent input following action selection. This prediction is supported by striatal recordings and contrasts with prior models of SPN representations. In our model, learning and action selection signals can be multiplexed without interference, enabling learning algorithms beyond those of standard temporal difference models.
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http://dx.doi.org/10.1101/2024.02.14.580408 | DOI Listing |
Crit Rev Anal Chem
January 2025
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.
Epilepsy is a serious neurological disease that impacts all facets of a patient's life, including their socioeconomic situation. The failure to identify underlying epileptic signatures in their early stages might result in severe harm to the central nervous system (CNS) and permanent adverse changes to some organs. Therefore, numerous antiepileptic drugs (AEDs are frequently used to control and treat the frequency of seizures.
View Article and Find Full Text PDFBiol Trace Elem Res
January 2025
College of Architecture and Environment, Sichuan University, Chengdu, 610065, China.
Exposure to vanadium (V) occurs through the ingestion of contaminated water, polluted soil, V-containing foods and medications, and the toxicity and absorption during the small intestine phase after oral ingestion play crucial roles in the ultimate health hazards posed by V. In this study, the human colon adenocarcinoma (Caco-2) cells were selected as an intestinal absorption model to investigate the uptake and cytotoxicity of vanadyl sulfate (VOSO) and sodium orthovanadate (NaVO). Our results confirmed the cytotoxic effects of V(IV) and V(V) and revealed a greater toxicity of V(IV) than V(V) towards Caco-2 cells.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Nuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution.
View Article and Find Full Text PDFBMC Oral Health
January 2025
Department of Dental Implantology, Jinan Stomatological Hospital, Jinan, 250002, Shandong, People's Republic of China.
Objective: To study the biomechanical changes induced by differences in perioral force in patients with missing anterior maxillary teeth at rest via finite element analysis (FEA).
Methods: Using conical beam CT (CBCT) images of a healthy person, models of the complete maxillary anterior dental region (Model A) and maxillary anterior dental region with a missing left maxillary central incisor (Model B) were constructed. The labial and palatine alveolar bone and tooth surface of the bilateral incisor and cusp regions were selected as the application sites, the resting perioral force was applied perpendicular to the tissue surface, and the changes in maxillary stress and displacement after the perioral force was simulated were analyzed.
Biochem Biophys Res Commun
December 2024
Department of Applied Sciences, Indian Institute of Information of Technology Allahabad, Prayagraj, Uttar Pradesh, 211012, India. Electronic address:
Prostate cancer is a widespread health issue that affects men worldwide. It is one of the most common forms of cancer, and its development is influenced by a combination of hereditary, epigenetic, environmental, age, and lifestyle factors. Given that it is the second most common cause of cancer-related deaths in men, it is crucial to comprehend its complex facets.
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