| 1. |
- Friling, Stina, et al.
(author)
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Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells
- 2009
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 106:18, s. 7613-7618
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Journal article (peer-reviewed)abstract
- Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.
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| 2. |
- Gabriel, Jens Peter, et al.
(author)
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Serotonergic Modulation of Locomotion in Zebrafish-Endogenous Release and Synaptic Mechanisms
- 2009
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In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 29:33, s. 10387-10395
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Journal article (peer-reviewed)abstract
- Serotonin (5-HT) plays an important role in shaping the activity of the spinal networks underlying locomotion in many vertebrate preparations. At larval stages in zebrafish, 5-HT does not change the frequency of spontaneous swimming; and it only decreases the quiescent period between consecutive swimming episodes. However, it is not known whether 5-HT exerts similar actions on the locomotor network at later developmental stages. For this, the effect of 5-HT on the fictive locomotor pattern of juvenile and adult zebrafish was analyzed. Bath-application of 5-HT (1-20 mu M) reduced the frequency of the NMDA-induced locomotor rhythm. Blocking removal from the synaptic cleft with the reuptake inhibitor citalopram had similar effects, suggesting that endogenous serotonin is modulating the locomotor pattern. One target for this modulation was the mid-cycle inhibition during locomotion because the IPSPs recorded in spinal neurons during the hyperpolarized phase were increased both in amplitude and occurrence by 5-HT. Similar results were obtained for IPSCs recorded in spinal neurons clamped at the reversal potential of excitatory currents (0 mV). 5-HT also slows down the rising phase of the excitatory drive recorded in spinal cord neurons when glycinergic inhibition is blocked. These results suggest that the decrease in the locomotor burst frequency induced by 5-HT is mediated by a potentiation of mid-cycle inhibition combined with a delayed onset of the subsequent depolarization.
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| 3. |
- Hallén, Kristofer, et al.
(author)
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mGluR-Mediated calcium oscillations in the lamprey: a computational model
- 2004
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In: Neurocomputing. - AMSTERDAM : Elsevier BV. - 0925-2312 .- 1872-8286. ; 58-60, s. 431-435, s. 431-435
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Journal article (peer-reviewed)abstract
- Slow Ca2+ oscillations caused by release from intracellular stores have been observed in neurons in the lamprey spinal cord. These oscillations are triggered by activation of metabotropic glutamate receptors on the cell surface. The pathway leading from receptor activation to the inositol triphosphate-mediated release of Ca2+ from the endoplasmatic reticulum has been modelled in order to facilitate further understanding of the nature of these oscillations. The model generates Ca2+ oscillations with a frequency range of 0.01–0.09 Hz. A prediction of the model is that the frequency will increase with a stronger extracellular glutamate signal.
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| 4. |
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| 5. |
- Huss, Mikael, et al.
(author)
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Role of A-current in lamprey locomotor network neurons
- 2003
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In: Neurocomputing. - : Elsevier BV. - 0925-2312 .- 1872-8286. ; 52-54, s. 295-300
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Journal article (peer-reviewed)abstract
- A compartmental model of lamprey central pattern generator neurons was built in order to examine the effects of a fast, transient, high-voltage-activated potassium current (A-current) found experimentally. The model consisted of a soma, a compartment corresponding to the axon initial segment, and a dendritic tree. The simulation showed that the A-current was necessary for repetitive spiking in the single neuron following current injection. The functional role of adding an A-current was also examined in a network model. In this model, the A-current stabilizes the swimming rhythm by making the burst cycle duration and the number of spikes per burst less variable. All these effects are also seen experimentally.
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| 6. |
- Huss, Mikael, et al.
(author)
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Roles of ionic currents in lamprey CPG neurons : a modeling study
- 2007
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 97:4, s. 2696-2711
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Journal article (peer-reviewed)abstract
- The spinal network underlying locomotion in the lamprey consists of a core network of glutamatergic and glycinergic interneurons, previously studied experimentally and through mathematical modeling. We present a new and more detailed computational model of lamprey locomotor network neurons, based primarily on detailed electrophysiological measurements and incorporating new experimental findings. The model uses a Hodgkin Huxley-like formalism and consists of 86 membrane compartments containing 12 types of ion currents. One of the goals was to introduce a fast, transient potassium current (K-t) and two sodium-dependent potassium currents, one faster (K-NaF) and one slower (K-NaS), in the model. Not only has the model lent support to the interpretation of experimental results but it has also provided predictions for further experimental analysis of single-network neurons. For example, K-t was shown to be one critical factor for controlling action potential duration. In addition, the model has proved helpful in investigating the possible influence of the slow afterhyperpolarization on repetitive firing during ongoing activation. In particular, the balance between the simulated slow sodium-dependent and calcium-dependent potassium currents has been explored, as well as the possible involvement of dendritic conductances.
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