| 1. |
- Björkman, Anders, et al.
(författare)
-
Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 2098-2106
-
Tidskriftsartikel (refereegranskat)abstract
- Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.
|
|
| 2. |
- Fuentes, Romulo, et al.
(författare)
-
Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:7, s. 1100-1108
-
Tidskriftsartikel (refereegranskat)abstract
- Specific motor symptoms of Parkinson's disease (PD) can be treated effectively with direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criteria. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but, from accumulated experience with the use of SCS in the management of chronic pain, it is known that the pathways most probably activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS results from direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brainstem nuclei, contributing to the initiation of locomotion. On the basis of the striking change in the corticostriatal oscillatory mode of neuronal activity induced by SCS, we propose that, through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low-frequency (< 30 Hz) oscillatory synchronization in the corticobasal ganglia circuits.
|
|
| 3. |
- Gabery, Sanaz, et al.
(författare)
-
Characterization of a rat model of Huntington's disease based on targeted expression of mutant huntingtin in the forebrain using adeno-associated viral vectors.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:6, s. 2789-2800
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (htt) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant htt is ubiquitously expressed, it has not been possible to establish clear structure-to-function relationships for the clinical aspects. In the present study, we have injected recombinant adeno-associated viral vectors of serotype 5 (rAAV5) expressing an 853-amino-acid fragment of htt with either 79 (mutant) or 18 (wild-type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of htt in the forebrain. Rats were followed for 6 months and compared with control rats. Neuropathological assessment showed long-term expression of the green fluorescent protein (GFP) transgene (used as a marker protein) and accumulation of htt inclusions in the cerebral cortex with the rAAV5-htt-79Q vectors. We estimated that around 10% of NeuN-positive cells in the cerebral cortex and 2% of DARPP-32 neurons in the striatum were targeted with the GFP-expressing vector. Formation of intracellular htt inclusions was not associated with neuronal loss, gliosis or microglia activation and did not lead to altered motor activity or changes in body weight. However, the same mutant htt vector caused orexin loss in the hypothalamus - another area known to be affected in HD. In conclusion, our results demonstrate that widespread forebrain expression of mutant htt can be achieved using rAAV5-vectors and suggest that this technique can be further explored to study region-specific effects of mutant htt or other disease-causing genes in the brain.
|
|
| 4. |
- Grealish, Shane, et al.
(författare)
-
Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease.
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; Jul 1, s. 2266-2278
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (>/= 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.
|
|
| 5. |
- Kallur, Therese, et al.
(författare)
-
Spatio-temporal dynamics, differentiation and viability of human neural stem cells after implantation into neonatal rat brain.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 34, s. 382-393
-
Tidskriftsartikel (refereegranskat)abstract
- Neural stem cells (NSCs) have attracted major research interest due to their potential use in cell replacement therapy. In patients, human cells are the preferred choice, one source of human NSCs being the brain of fetuses. The aims of the present study were to explore the long-term differentiation, mobility and viability of NSCs derived from the human fetal striatum in response to intracerebral implantation. To investigate long-term spatio-temporal and functional dynamics of grafts in vivo by magnetic resonance imaging, these cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles prior to implantation. SPIO-labeling of human NSCs left the quantitative profile of the proliferation, cell composition and differentiation capacity of the cells in vitro unaltered. Also after transplantation, the phenotypes after long-term cell differentiation were not significantly different from naïve cells. Upon transplantation, we detected a hypointensity corresponding to the striatal graft location in all animals and persisting for at least 4 months. The hypointense signal appeared visually similar both in location and in volume over time. However, quantitative volumetric analysis showed that the detectable, apparent graft volume decreased significantly from 3 to 16 weeks. Finally, the human NSCs were not proliferating after implantation, indicating lack of tumor formation. These cells are thus a promising candidate for translationally relevant investigations for stem cell-based regenerative therapies.
|
|
| 6. |
- Kokaia, Merab
(författare)
-
Seizure-induced neurogenesis in the adult brain.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33:6, s. 1133-1138
-
Tidskriftsartikel (refereegranskat)abstract
- It is well established that seizures increase adult neurogenesis in the subventricular and subgranular zones, the most neurogenic regions of the adult rodent and apparently human brain. However, the role of increased neurogenesis in these areas in seizure generation (ictogenesis) and epileptogenesis remains elusive. It is of utmost importance to explore how the cells that are born in response to epileptic seizures are functionally integrated into the existing neuronal networks, and how this integration would contribute to the excitability of this network. This will determine whether increased neurogenesis is beneficial or counteractive to ictogenesis and epileptogenesis. Some of the crucial factors affecting the functional integration of newborn cells seem to be excessive neuronal activity and/or inflammatory microenvironment, both associated with acute, as well as chronic, epileptic conditions. This review will focus on aspects of the functional integration of newborn cells in animal models of epilepsy with various degrees of seizure severity and associated microenvironmental alterations in the brain tissue.
|
|
| 7. |
- Ledri, Marco, et al.
(författare)
-
Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.
- 2012
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 1971-1983
-
Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditions, the endogenous excitability regulator neuropeptide Y (NPY) has been shown to modulate afferent inputs onto dentate gyrus CCK-basket cells, providing a possible novel mechanism for excitability control in the hippocampus. Using GAD65-GFP mice for CCK-basket cell identification, and whole-cell patch-clamp recordings, we explored whether the effect of NPY on afferent synapses to CCK-basket cells is modified in the hyper-excitable dentate gyrus. To induce a hyper-excitable state, recurrent seizures were evoked by electrical stimulation of the hippocampus using the well-characterized rapid kindling protocol. The frequency of spontaneous and miniature excitatory and inhibitory post-synaptic currents recorded in CCK-basket cells was decreased by NPY. The excitatory post-synaptic currents evoked in CCK-basket cells by optogenetic activation of principal neurons were also decreased in amplitude. Interestingly, we observed an increased proportion of spontaneous inhibitory post-synaptic currents with slower rise times, indicating that NPY may inhibit gamma aminobutyric acid release preferentially in peri-somatic synapses. These findings indicate that increased levels and release of NPY observed after seizures can modulate afferent inputs to CCK-basket cells, and therefore alter their impact on the oscillatory network activity and excitability in the hippocampus.
|
|
| 8. |
- Ulusoy, Ayse, et al.
(författare)
-
Co-expression of C-terminal truncated alpha-synuclein enhances full-length alpha-synuclein-induced pathology.
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:3, s. 409-422
-
Tidskriftsartikel (refereegranskat)abstract
- Lewy bodies, which are a pathological hallmark of Parkinson's disease, contain insoluble polymers of alpha-synuclein (alphasyn). Among the different modifications that can promote the formation of toxic alphasyn species, C-terminal truncation is among the most abundant alterations in patients with Parkinson's disease. In vitro, C-terminal truncated alphasyn aggregates faster and sub-stoichiometric amounts of C-terminal truncated alphasyn promote aggregation of the full-length alphasyn (alphasynFL) and induce neuronal toxicity. To address in vivo the putative stimulation of alphasyn-induced pathology by the presence of truncated alphasyn, we used recombinant adeno-associated virus to express either alphasynFL or a C-terminal truncated alphasyn (1-110) in rats. We adjusted the recombinant adeno-associated virus vector concentrations so that either protein alone led to only mild to moderate axonal pathology in the terminals of nigrostriatal dopamine neurons without frank cell loss. When these two forms of alphasyn were co-expressed at these pre-determined levels, it resulted in a more aggressive pathology in fiber terminals as well as dopaminergic cell loss in the substantia nigra. Using an antibody that did not detect the C-terminal truncated alphasyn (1-110) but only alphasynFL, we demonstrated that the co-expressed truncated protein promoted the progressive accumulation of alphasynFL and formation of larger pathological accumulations. Moreover, in the co-expression group, three of the eight animals showed apomorphine-induced turning, suggesting prominent post-synaptic alterations due to impairments in the dopamine release, whereas the mild pathology induced by either form alone did not cause motor abnormalities. Taken together these data suggest that C-terminal truncated alphasyn can interact with and exacerbate the formation of pathological accumulations containing alphasynFL in vivo.
|
|
| 9. |
- Weibull, Andreas, et al.
(författare)
-
Cerebral and clinical effects of short-term hand immobilisation.
- 2011
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33, s. 699-704
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, functional changes in the sensorimotor cortex following unilateral hand immobilisation were investigated in 11 healthy volunteers. Sensory and motor function of both hands was also assessed. Cortical activation was monitored with functional magnetic resonance imaging at 3 T. All examinations were performed prior to and directly after 72 h of immobilisation of the dominant hand and wrist. Following unilateral immobilisation, cortical activation increased substantially during tactile stimulation of the non-immobilised hand. This was particularly evident in the ipsilateral somatosensory cortex. Additionally, a redistribution of hemispheric dominance towards zero lateralisation was seen. A bilateral cortical activation increase was also seen during performance of a finger-tapping task by the non-immobilised hand, although this increase was less prominent than during tactile stimulation. In contrast, performance of the finger-tapping task with the immobilised hand resulted in an activation decrease, predominantly in the ipsilateral sensorimotor cortex. This site was anatomically close to the regional activation increase of the non-immobilised hand. These functional changes were associated with reduced grip strength, dexterity and tactile discrimination of the immobilised hand, and simultaneously improved tactile discrimination of the non-immobilised hand. This suggests that brain adaptation following hand immobilisation includes inter-hemispheric dynamics. In summary, the improved sensory function of the non-immobilised hand following unilateral immobilisation is associated with cortical expansion, predominantly contralateral to the immobilised hand, and a redistribution of hemispheric dominance. Both cortical and clinical effects of immobilisation were identified after 72 h, suggesting rapid inter-hemispheric plasticity using existing neural substrates.
|
|
| 10. |
- Zapka, Manuela, et al.
(författare)
-
Night-time neuronal activation of Cluster N in a day- and night-migrating songbird
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:4, s. 619-624
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetic compass orientation in a night-migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night-migrants performing magnetic compass-guided behaviour at night, whereas no activation is observed during the day, and covering up the birds' eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light-dependent magnetic compass information in night-migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day- and night-migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim-light at night, but not under full room-light conditions during the day. These data suggest that, in day- and night-migratory meadow pipits, the light-dependent magnetic compass, which requires an active Cluster N, may only be used during night-time, whereas another magnetosensory mechanism and/or other reference system(s), like the sun or polarized light, may be used as primary orientation cues during the day.
|
|
