| 1. |
- Böhme, Rebecca, et al.
(författare)
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Rebound excitation triggered by synaptic inhibition in cerebellar nuclear neurons is suppressed by selective T-type calcium channel block
- 2011
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 106:5, s. 2653-2661
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Tidskriftsartikel (refereegranskat)abstract
- Following hyperpolarizing inputs, many neurons respond with an increase in firing rate, a phenomenon known as rebound excitation. Rebound excitation has been proposed as a mechanism to encode and process inhibitory signals and transfer them to target structures. Activation of low-voltage-activated T-type calcium channels and the ensuing low-threshold calcium spikes is one of the mechanisms proposed to support rebound excitation. However, there is still not enough evidence that the hyperpolarization provided by inhibitory inputs, particularly those dependent on chloride ions, is adequate to deinactivate a sufficient number of T-type calcium channels to drive rebound excitation on return to baseline. Here, this issue was investigated in the deep cerebellar nuclear neurons (DCNs), which receive the output of the cerebellar cortex conveyed exclusively by the inhibitory Purkinje cells and are also known to display rebound excitation. Using cerebellar slices and whole cell recordings of large DCNs, we show that a novel piperidine-based compound that selectively antagonizes T-type calcium channel activity, 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydropyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2), suppressed rebound excitation elicited by current injection as well as by synaptic inhibition, whereas other electrophysiological properties of large DCNs were unaltered. Furthermore, TTA-P2 suppressed transient high-frequency rebounds found in DCNs with low-threshold spikes as well as the slow rebounds present in DCNs without low-threshold spikes. These findings demonstrate that chloride-dependent synaptic inhibition effectively triggers T-type calcium channel-mediated rebounds and that the latter channels may support slow rebound excitation in neurons without low-threshold spikes.
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| 2. |
- Deserno, Lorenz, et al.
(författare)
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Reinforcement Learning and Dopamine in Schizophrenia : Dimensions of Symptoms or Specific Features of a Disease Group?
- 2013
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Ingår i: Frontiers in Psychiatry. - Lausanne, Switzerland : Frontiers Research Foundation. - 1664-0640. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Abnormalities in reinforcement learning are a key finding in schizophrenia and have been proposed to be linked to elevated levels of dopamine neurotransmission. Behavioral deficits in reinforcement learning and their neural correlates may contribute to the formation of clinical characteristics of schizophrenia. The ability to form predictions about future outcomes is fundamental for environmental interactions and depends on neuronal teaching signals, like reward prediction errors. While aberrant prediction errors, that encode non-salient events as surprising, have been proposed to contribute to the formation of positive symptoms, a failure to build neural representations of decision values may result in negative symptoms. Here, we review behavioral and neuroimaging research in schizophrenia and focus on studies that implemented reinforcement learning models. In addition, we discuss studies that combined reinforcement learning with measures of dopamine. Thereby, we suggest how reinforcement learning abnormalities in schizophrenia may contribute to the formation of psychotic symptoms and may interact with cognitive deficits. These ideas point toward an interplay of more rigid versus flexible control over reinforcement learning. Pronounced deficits in the flexible or model-based domain may allow for a detailed characterization of well-established cognitive deficits in schizophrenia patients based on computational models of learning. Finally, we propose a framework based on the potentially crucial contribution of dopamine to dysfunctional reinforcement learning on the level of neural networks. Future research may strongly benefit from computational modeling but also requires further methodological improvement for clinical group studies. These research tools may help to improve our understanding of disease-specific mechanisms and may help to identify clinically relevant subgroups of the heterogeneous entity schizophrenia.
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| 3. |
- Himmelbach, Marc, et al.
(författare)
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20 years later : A second look on DF’s motor behaviour
- 2012
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Ingår i: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 50:1, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- The so-called action vs. perception model represents one of the currently dominating models addressing visual processing in primates. One of the crucial cornerstones of the action vs. perception model of visual processing is the dissociation of impaired perception versus intact visuomotor control in neurological patients with visual form agnosia (VFA). In fact, virtually all evidence related to VFA supporting the model was reported from only one patient: patient D.F. Through the last two decades D.F. became as important as only very few other exemplar cases in the neurosciences. However, a large corpus of experiments with this individual used methods that were insufficient to reveal less obvious impairments on a single subject level. We reanalysed the data of D.F. and identified basic visuomotor impairments that had been overlooked so far. Our reanalysis underlines the fact that the widespread and popular presentation of strong dissociations between distinct visual systems seems to be exaggerated.
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