Impairments of synaptic plasticity are a hallmark of several neurological disorders, including Parkinson's disease (PD) which results from the progressive loss of dopaminergic neurons of the substantia nigra pars compacta leading to abnormal activity within the basal ganglia (BG) network and pathological motor symptoms. Indeed, disrupted plasticity at corticostriatal glutamatergic synapses, the gateway of the BG, is correlated to the onset of PD-related movement disorders and thus has been proposed to be a key neural substrate regulating information flow and motor function in BG circuits. However, a critical question is whether similar plasticity impairments could occur at other glutamatergic connections within the BG that would also affect the inhibitory influence of the network on the motor thalamus. Here, we show that long-term plasticity at subthalamo-nigral glutamatergic synapses (STN-SNr) sculpting the activity patterns of nigral neurons, the main output of the network, is also affected in experimental parkinsonism. Using whole-cell patch-clamp in acute rat brain slices, we describe a molecular pathway supporting an activity-dependent long-term depression of STN-SNr synapses through an NMDAR-and D1/5 dopamine receptor-mediated endocytosis of synaptic AMPA glutamate receptors. We also show that this plastic property is lost in an experimental rat model of PD but can be restored through the recruitment of dopamine D1/5 receptors. Altogether, our findings suggest that pathological impairments of subthalamo-nigral plasticity may enhance BG outputs and thereby contribute to PD-related motor dysfunctions.
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http://dx.doi.org/10.1523/JNEUROSCI.1681-13.2013 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Bochum 44780, Germany.
The novelty, saliency, and valency of ongoing experiences potently influence the firing rate of the ventral tegmental area (VTA) and the locus coeruleus (LC). Associative experience, in turn, is recorded into memory by means of hippocampal synaptic plasticity that is regulated by noradrenaline sourced from the LC, and dopamine, sourced from both the VTA and LC. Two persistent forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD) support the encoding of different kinds of spatial experience.
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JAMA Netw Open
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Division of Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Importance: Data characterizing the severity and changing prevalence of bone mineral density (BMD) deficits and associated nonfracture consequences among childhood cancer survivors decades after treatment are lacking.
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JAMA Netw Open
January 2025
National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
Importance: Sleep disorders and mild cognitive impairment (MCI) commonly coexist in older adults, increasing their risk of developing dementia. Long-term tai chi chuan has been proven to improve sleep quality in older adults. However, their adherence to extended training regimens can be challenging.
View Article and Find Full Text PDFBJS Open
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Department of Cardiology, Thorax Centre, Cardiovascular Institute, Erasmus MC, Rotterdam, The Netherlands.
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