Many motor skills are learned by comparing ongoing behavior to internal performance benchmarks. Dopamine neurons encode performance error in behavioral paradigms where error is externally induced, but it remains unknown whether dopamine also signals the quality of natural performance fluctuations. Here, we record dopamine neurons in singing birds and examine how spontaneous dopamine spiking activity correlates with natural fluctuations in ongoing song. Antidromically identified basal ganglia-projecting dopamine neurons correlate with recent, and not future, song variations, consistent with a role in evaluation, not production. Furthermore, maximal dopamine spiking occurs at a single vocal target, consistent with either actively maintaining the existing song or shifting the song to a nearby form. These data show that spontaneous dopamine spiking can evaluate natural behavioral fluctuations unperturbed by experimental events such as cues or rewards.
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http://dx.doi.org/10.1016/j.celrep.2022.110574 | DOI Listing |
Cell-type-specific activation of parvalbumin (PV)-expressing neurons in the external globus pallidus (GPe) through optogenetics has shown promise in facilitating long-lasting movement dysfunction recovery in mice with Parkinson's disease. However, its translational potential is hindered by adverse effects stemming from the invasive implantation of optical fibers into the brain. In this study, we have developed a non-invasive optogenetics approach, utilizing focused ultrasound-triggered mechanoluminescent nanotransducers to enable remote photon delivery deep in the brain for genetically targeted neuromodulation.
View Article and Find Full Text PDFLymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins in Parkinson's disease (PD). This study investigates the role of neuronal LAG3 in mediating the binding, uptake, and propagation of α-synuclein (αSyn) preformed fibrils (PFFs). Using neuronal LAG3 conditional knockout mice and human induced pluripotent stem cells-derived dopaminergic (DA) neurons, we demonstrate that LAG3 expression is critical for pathogenic αSyn propagation.
View Article and Find Full Text PDFParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, primarily due to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Factors contributing to this neuronal degeneration include mitochondrial dysfunction, oxidative stress, and neuronal excitotoxicity. Despite extensive research, the exact etiology of PD remains unclear, with both genetic and environmental factors playing significant roles.
View Article and Find Full Text PDFAt cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction of the glutamate transporter 1 (GLT-1) in the nucleus accumbens (NAc) has also been proposed as a mechanism underlying drug addiction. However, the cellular and synaptic impact of GLT-1 alterations in the NAc remain unclear.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Pathology, School of Veterinary Medicine, University of São Paulo, Sao Paulo, Brazil.
Autism spectrum disorder (ASD) is a complex developmental disorder characterized by several behavioral impairments, especially in socialization, communication, and the occurrence of stereotyped behaviors. In rats, prenatal exposure to valproic acid (VPA) induces autistic-like behaviors. Previous studies by our group have suggested that the autistic-like phenotype is possibly related to dopaminergic system modulation because tyrosine hydroxylase (TH) expression was affected.
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