TY  - JOUR
A1  - Andreska, Thomas
A1  - Lüningschrör, Patrick
A1  - Wolf, Daniel
A1  - McFleder, Rhonda L.
A1  - Ayon-Olivas, Maurilyn
A1  - Rattka, Marta
A1  - Drechsler, Christine
A1  - Perschin, Veronika
A1  - Blum, Robert
A1  - Aufmkolk, Sarah
A1  - Granado, Noelia
A1  - Moratalla, Rosario
A1  - Sauer, Markus
A1  - Monoranu, Camelia
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
A1  - Stigloher, Christian
A1  - Sendtner, Michael
T1  - DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons
JF  - Cell Reports
N2  - Highlights
• Dopamine receptor-1 activation induces TrkB cell-surface expression in striatal neurons
• Dopaminergic deficits cause TrkB accumulation and clustering in the ER
• TrkB clusters colocalize with cargo receptor SORCS-2 in direct pathway striatal neurons
• Intracellular TrkB clusters fail to fuse with lysosomes after dopamine depletion

Summary
Disturbed motor control is a hallmark of Parkinson’s disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.
KW  - motor learning
KW  - cortico-striatal synapse
KW  - basal ganglia
KW  - direct pathway
KW  - DRD1
KW  - dSPN
KW  - BDNF
KW  - TrkB
KW  - synaptic plasticity
KW  - GPCR
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349932
VL  - 42
IS  - 6
ER  - 
TY  - JOUR
A1  - Nguemeni, Carine
A1  - Stiehl, Annika
A1  - Hiew, Shawn
A1  - Zeller, Daniel
T1  - No Impact of Cerebellar Anodal Transcranial Direct Current Stimulation at Three Different Timings on Motor Learning in a Sequential Finger-Tapping Task
JF  - Frontiers in Human Neuroscience
N2  - Background: Recently, attention has grown toward cerebellar neuromodulation in motor learning using transcranial direct current stimulation (tDCS). An important point of discussion regarding this modulation is the optimal timing of tDCS, as this parameter could significantly influence the outcome. Hence, this study aimed to investigate the effects of the timing of cerebellar anodal tDCS (ca-tDCS) on motor learning using a sequential finger-tapping task (FTT).
Methods: One hundred and twenty two healthy young, right-handed subjects (96 females) were randomized into four groups (During\(_{sham}\), Before, During\(_{real}\), After). They performed 2 days of FTT with their non-dominant hand on a custom keyboard. The task consisted of 40 s of typing followed by 20 s rest. Each participant received ca-tDCS (2 mA, sponge electrodes of 25 cm\(^{2}\), 20 min) at the appropriate timing and performed 20 trials on the first day (T1, 20 min). On the following day, only 10 trials of FTT were performed without tDCS (T2, 10 min). Motor skill performance and retention were assessed.
Results: All participants showed a time-dependent increase in learning. Motor performance was not different between groups at the end of T1 (p = 0.59). ca-tDCS did not facilitate the retention of the motor skill in the FTT at T2 (p = 0.27). Thus, our findings indicate an absence of the effect of ca-tDCS on motor performance or retention of the FTT independently from the timing of stimulation.
Conclusion: The present results suggest that the outcome of ca-tDCS is highly dependent on the task and stimulation parameters. Future studies need to establish a clear basis for the successful and reproducible clinical application of ca-tDCS.
KW  - cerebellar tDCS
KW  - finger-tapping task
KW  - timing
KW  - motor learning
KW  - task retention
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225477
SN  - 1662-5161
VL  - 15
ER  -