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The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to spontaneous firing, are described. In comparison with dorsal VTA DA neurons, ventrally located VTA neurons (as measured by cell body location) possess a shorter total dendritic length and simpler dendritic architecture, and exhibit the most irregular firing patterns among DA neurons. In contrast, for DA neurons in the SNc, the higher irregularity of firing was related to a smaller dendritic domain, as measured by convex hull volumes. However, firing properties were also related to the specific regional distribution of the dendritic tree. Thus, VTA DA neurons with a larger extension of their dendritic tree within the parabrachial pigmented (PBP) nucleus fired more regularly compared with those with relatively more dendrites extending outside the PBP. For DA neurons in the SNc, enhanced firing irregularity was associated with a smaller proportion of dendrites penetrating the substantia nigra pars reticulata. These results suggest that differences in dendritic morphology contribute to the firing properties of individual DA neurons, and that the existence of region-specific synaptic connectivity rules that shape firing diversity.
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http://dx.doi.org/10.3389/fncir.2021.769342 | DOI Listing |
Vavilovskii Zhurnal Genet Selektsii
November 2024
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Parkinson's disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucleinopathy is associated with abnormalities in the dopaminergic brain system.
View Article and Find Full Text PDFJ Control Release
December 2024
Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213003, China. Electronic address:
Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.
Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.
Trends Neurosci
December 2024
Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, UFRGS, Porto Alegre, Brazil; Department of Pharmacology, UFRGS, Porto Alegre, Brazil; McGill Centre for Studies in Aging, McGill University, Montreal, Quebec, Canada; Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address:
In a recent study, Haas, Bravo, and colleagues integrated optogenetic stimulation with simultaneous functional in vivo positron emission tomography (PET)/magnetic resonance imaging (MRI) measurements in rats. By activating the nigrostriatal pathway in the substantia nigra pars compacta (SNc), they observed concurrent metabolic and hemodynamic fluctuations associated with the dopaminergic pathway in living animals at the whole-brain level.
View Article and Find Full Text PDFNeuroimage Clin
December 2024
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Progressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a network of regions including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting-state functional MRI (rs-fMRI) differed between PSP-Richardson's syndrome (PSP-RS) and the cortical and subcortical clinical variants of PSP. Structural MRI and rs-fMRI scans were collected for 36 PSP-RS, 25 PSP-cortical and 34 PSP-subcortical participants who met the Movement Disorder Society PSP clinical criteria.
View Article and Find Full Text PDFCureus
November 2024
Integrative Medicine, Division of Yoga, Ministry of Ayush, Central Research Institute of Yoga and Naturopathy (CRIYN), Nagamangala, IND.
Introduction Parkinson's disease (PD) is primarily thought to be brought on by the death of dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia. Communication difficulties are a common symptom of PD, affecting both motor speech and language systems. These challenges significantly impact the quality of life by reducing participation in communication, leading to social withdrawal, and increasing the risk of social isolation and stigma among individuals with PD.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!