| 1. |
- Fieblinger, Tim, et al.
(författare)
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Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses.
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| 2. |
- Liebmann, Thomas, et al.
(författare)
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A Noncanonical Postsynaptic Transport Route for a GPCR Belonging to the Serotonin Receptor Family
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:50, s. 17998-18008
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Tidskriftsartikel (refereegranskat)abstract
- Postsynaptic receptor trafficking plays an essential role in tuning neurotransmission and signal plasticity and has emerged as a potential therapeutic target in neuropsychiatric disease. Using a novel application of fluorescence recovery after photobleaching in rat hippocampal neurons, we examined transport from the soma to dendrites of seven G-protein-coupled receptors (GPCRs) implicated in mood disorders. Most GPCRs were delivered to dendrites via lateral diffusion, but one GPCR, the serotonin 1B receptor (5-HT1B), was delivered to the dendrites in secretory vesicles. Within the dendrites, 5-HT1B were stored in a reservoir of accessible vesicles that were recruited to preferential sites in plasma membrane, as observed with superecliptic pHluorin labeling. After membrane recruitment, 5-HT1B transport via lateral diffusion and temporal confinement to inhibitory and excitatory synapses was monitored by single particle tracking. These results suggest an alternative mechanism for control of neuronal activity via a GPCR that has been implicated in mood regulation.
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