| 1. |
- Brys, Ivani, et al.
(författare)
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Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists
- 2018
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 302, s. 155-168
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.
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| 2. |
- Ivica, Nedjeljka, et al.
(författare)
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Changes in neuronal activity of cortico-basal ganglia-thalamic networks induced by acute dopaminergic manipulations in rats
- 2018
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X. ; 47:3, s. 236-250
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Tidskriftsartikel (refereegranskat)abstract
- The basal ganglia are thought to be particularly sensitive to changes in dopaminergic tone, and the realization that reduced dopaminergic signaling causes pronounced motor dysfunction is the rationale behind dopamine replacement therapy in Parkinson's disease. It has, however, proven difficult to identify which neurophysiological changes that ultimately lead to motor dysfunctions. To clarify this, we have here recorded neuronal activity throughout the cortico-basal ganglia-thalamic circuits in freely behaving rats during periods of immobility following acute dopaminergic manipulations, involving both vesicular dopamine depletion and antagonism of D1 and D2 type dopamine receptors. Synchronized and rhythmic activities were detected in the form of betaband oscillations in local field potentials and as cortical entrainment of action potentials in several basal ganglia structures. Analyses of the temporal development of synchronized oscillations revealed a spread from cortex to gradually also include deeper structures. In addition, firing rate changes involving neurons in all parts of the network were observed. These changes were typically relatively balanced within each structure, resulting in negligible net rate changes. Animals treated with D1 receptor antagonist showed a rapid onset of hypokinesia that preceded most of the neurophysiological changes, with the exception of these balanced rate changes. Parallel rate changes in functionally coupled ensembles of neurons in different structures may therefore be the first step in a cascade of neurophysiological changes underlying motor symptoms in the parkinsonian state. We suggest that balanced rate changes in distributed networks are possible mechanism of disease that should be further investigated in conditions involving dopaminergic dysfunction.
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