Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor and non-motor symptoms. The underlying pathology of non-motor symptoms is poorly understood. Discussed are pathological changes of extrastriatal brain structures. In this study, we characterized histopathological alterations of extrastriatal brain structures in the 6-hydroxydopamine (6-OHDA) PD animal model. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum or medial forebrain bundle of adult male mice. Loss of tyrosine hydroxylase positive (TH) fibers as well as glia activation was quantified following stereological principles. Loss of dopaminergic innervation was further investigated by western-blotting. As expected, 6-OHDA injection into the nigrostriatal route induced retrograde degeneration of dopaminergic neurons within the substantia nigra pars compacta (SNpc), less so within the ventral tegmental area. Furthermore, we observed a region-specific drop of TH projection fiber density in distinct cortical regions. This pathology was most pronounced in the cingulate- and motor cortex, whereas the piriform cortex was just modestly affected. Loss of cortical TH fibers was not paralleled by microglia or astrocyte activation. Our results demonstrate that the loss of dopaminergic neurons within the substantia nigra pars compacta is paralleled by a cortical dopaminergic denervation in the 6-OHDA model. This model serves as a valuable tool to investigate mechanisms operant during cortical pathology in PD patients. Further studies are needed to understand why cortical dopaminergic innervation is lost in this model, and what functional consequence is associated with the observed denervation.
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http://dx.doi.org/10.1007/s12035-017-0637-9 | DOI Listing |
Proc Natl Acad Sci U S A
November 2024
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544.
Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval.
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September 2024
The Laboratory of Brain and Cognition, The National Institute of Mental Health, 10 Center Drive, Bethesda, MD 20982, United States.
The extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g. faces, scenes, and tools).
View Article and Find Full Text PDFPhysiol Behav
October 2024
Departments of Psychiatry, New York University Grossman School of Medicine, 435 East 30th Street, New York, NY 10016, USA; Departments of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, 435 East 30th Street, New York, NY 10016, USA. Electronic address:
It was previously shown in striatal slices obtained from male rats that insulin excites cholinergic interneurons and increases dopamine (DA) release via α4β2 nicotinic receptors on DA terminals. The effect of insulin on DA release was blocked either by maintaining rats on a high sugar-high fat (HS-HF) diet that induced hyperinsulinemia and nucleus accumbens (NAc) insulin receptor insensitivity, or applying the α4β2 antagonist DHβE. In vivo, NAc shell insulin inactivation decreased a glucose lick microstructure parameter indicative of hedonic impact in male and female rats, and prevented flavor-nutrient learning, tested only in males.
View Article and Find Full Text PDFbioRxiv
February 2024
The Laboratory of Brain and Cognition, The National Institute of Mental Health, MD, USA.
Extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g., faces, scenes, and tools).
View Article and Find Full Text PDFNeuroimage Clin
June 2024
Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland; CIBM Center for Biomedical Imaging, Geneva, Switzerland. Electronic address:
A proportion of patients clinically diagnosed with Parkinson's disease (PD) can have a I-FP-CIT-SPECT scan without evidence of dopaminergic deficit (SWEDD), generating a debate about the underlying biological mechanisms. This study investigated differences in clinical features, I-FP-CIT binding, molecular connectivity, as well as clinical and imaging progression between SWEDD and PD patients. We included 36 SWEDD, 49 de novo idiopathic PD, and 49 healthy controls with I-FP-CIT-SPECT from the Parkinson's Progression Markers Initiative.
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