Dopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca imaging to monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) simultaneously in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that increasing and decreasing DA biases striatal activity toward the direct and indirect pathways, respectively, by changing the overall number of SPNs recruited during behavior in a manner not predicted by existing models of DA function. This modulation is drastically altered in a model of Parkinson's disease. Our results reveal a previously unappreciated population-level influence of DA on striatal output and provide novel insights into the pathophysiology of Parkinson's disease.
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http://dx.doi.org/10.7554/eLife.68041 | DOI Listing |
Environ Sci Technol
January 2025
State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, PR China.
Pyrogenic carbons (PCs), with varying structures depending on the materials and thermal treatment conditions, have been extensively used to enhance anaerobic digestion by mediating electron transfer. However, the underlying mechanism has yet to be explored. Herein, the redirection and enhancement of the direct interspecies electron transfer (DIET) pathway were evidenced, along with the upregulated electrochemical properties and structural proteins in the methanogenic consortia.
View Article and Find Full Text PDFApoptosis
January 2025
Department of Breast Cancer Surgery, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, No. 519 Beijing East Road, Nanchang, Jiangxi, 330029, China.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital (Yiwu), Zhejiang University School of Medicine, Hangzhou, 310058, China.
Cancer stem cells (CSCs) typically reside in perivascular niches, but whether endothelial cells of blood vessels influence the stemness of cancer cells remains poorly understood. This study revealed that endothelial cell-specific GLTSCR1 deletion promotes colorectal cancer (CRC) tumorigenesis and metastasis by increasing cancer cell stemness. Mechanistically, knocking down GLTSCR1 induces the transformation of endothelial cells into tip cells by regulating the expression of Neuropilin-1 (NRP1), thereby increasing the direct contact and interaction between endothelial cells and tumour cells.
View Article and Find Full Text PDFLeukemia
January 2025
Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany.
Refractory disease and relapse are major challenges in acute myeloid leukemia (AML) therapy attributed to survival of leukemic stem cells (LSC). To target LSCs, antibody-drug conjugates (ADCs) provide an elegant solution, combining the specificity of antibodies with highly potent payloads. We aimed to investigate if FLT3-20D9h3-ADCs delivering either the DNA-alkylator duocarmycin (DUBA) or the microtubule-toxin monomethyl auristatin F (MMAF) can eradicate quiescent LSCs.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Hematology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China.
A study in the Enshi Region between Sept-Nov 2023 assessed medical staff's knowledge, attitude, and practice regarding multiple myeloma. The disease significantly impacts physical health, quality of life, and mental well-being. Medical professionals play crucial roles in its prevention and treatment.
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