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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618387PMC
http://dx.doi.org/10.1523/JNEUROSCI.1681-13.2013DOI Listing

Publication Analysis

Top Keywords

long-term depression
8
lost experimental
8
experimental parkinsonism
8
glutamatergic synapses
8
plasticity
5
dopamine-dependent long-term
4
depression subthalamo-nigral
4
synapses
4
subthalamo-nigral synapses
4
synapses lost
4

Similar Publications

Oppositional and competitive instigation of hippocampal synaptic plasticity by the VTA and locus coeruleus.

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.

View Article and Find Full Text PDF

Background: Young adults (15-24 years old) living with HIV may experience pressure both from HIV infection and social role change problems, resulting in a series of psychological problems such as depression and anxiety. Effective psychological intervention can improve their mental health and quality of life.

Objective: The study aims to explore the effectiveness of VR-based mental intervention on young adults living with HIV.

View Article and Find Full Text PDF

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.

Objective: To evaluate risk for moderate and severe BMD deficits in survivors and to identify long-term consequences of BMD deficits.

Design, Setting, And Participants: This cohort study used cross-sectional and longitudinal data from the St Jude Lifetime (SJLIFE) cohort, a retrospectively constructed cohort with prospective follow-up.

View Article and Find Full Text PDF

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 PDF

Background: Contrary to the impact of screening, the effect of long-term surveillance on the quality of life of patients with an abdominal aortic aneurysm is not well known. Therefore, the aim of this study was to describe patient-reported outcomes of patients with an abdominal aortic aneurysm approaching the surgical threshold.

Methods: This multicentre, observational cohort study included patients with an abdominal aortic aneurysm with a maximum aneurysm diameter of greater than or equal to 40 mm.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!