Spindle burst like spike discharge oscillations in organotypic cultures of neonatal rat cortex

Early network oscillations and spindle bursts are typical patterns of spontaneous rhythmic activity in cortical networks of neonatal rodents in vivo and in vitro. The latter can also be triggered in vivo by stimulation of afferent inputs. The mechanisms underlying such oscillations undergo profound developmental changes in the first postnatal weeks. Their possible role in cortical development is postulated but not known in detail. We have studied spontaneous and evoked patterns of activity in organotypic cultures of slices from neonatal rat cortex grown on multielectrode arrays (MEAs) for extracellular single- and multi-unit recording. Episodes of spontaneous spike discharge oscillations at 7 - 25 Hz lasting for 0.6 - 3 seconds appeared in about half of these cultures spontaneously and could be triggered by electrical stimulation of few distinct electrodes. These oscillations usually covered only restricted areas of the slices. Besides oscillations, single population bursts that spread in a wavelike manner over the whole slice also appeared spontaneously and were triggered by electrical stimulation. In most but not all cultures, population bursts preceded the oscillations. Both population bursts and spike discharge oscillations required intact glutamatergic synaptic transmission since they were suppressed by the AMPA/kainate glutamate receptor antagonist CNQX. The NMDA antagonist d-APV suppressed the oscillations but not the population bursts, suggesting an involvement of NMDA receptors in the oscillations. These findings show that spindle burst like cortical rhythms are reproduced in organotypic cultures of neonatal cortex. The culture model thus allows investigating the role of such rhythms in cortical circuit formation. Supported by SNF grant No. 3100A0-107641/1.

Modulation of parvalbumin expression in the motor cortex of parkinsonian rats

Dopamine deficiency in Parkinson's disease leads to numerous molecular changes in basal ganglia. However, the consequences of these changes on the motor cortex remain unclear. Here we show that the immunoreactivity of parvalbumin, which is expressed in GABAergic interneurons, increases in the primary motor cortex of parkinsonian rats. This increase can be reversed by a subsequent lesion of the subthalamic nucleus. These results suggest that dopamine deficiency induces reversible changes in GABAergic cortical cells, which might be linked with parkinsonian symptoms.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

The role of the human posterior parietal cortex in memory-guided saccade execution: a double-pulse transcranial magnetic stimulation study

The present study investigated the role of the right posterior parietal cortex (PPC) in the triggering of memory-guided saccades by means of double-pulse transcranial magnetic stimulation (dTMS). Shortly before saccade onset, dTMS with different interstimulus intervals (ISI; 35, 50, 65 or 80 ms) was applied. For contralateral saccades, dTMS significantly decreased saccadic latency with an ISI of 80 ms and increased saccadic gain with an ISI of 65 and 80 ms. Together with the findings of a previous study during frontal eye field (FEF) stimulation the present results demonstrate similarities and differences between both regions in the execution of memory-guided saccades. Firstly, dTMS facilitates saccade triggering in both regions, but the timing is different. Secondly, dTMS over the PPC provokes a hypermetria of contralateral memory-guided saccades that was not observed during FEF stimulation. The results are discussed within the context of recent neurophysiological findings in monkeys.

Mapping of direction and muscle representation in the human primary motor cortex controlling thumb movements

Larger body parts are somatotopically represented in the primary motor cortex (M1), while smaller body parts, such as the fingers, have partially overlapping representations. The principles that govern the overlapping organization of M1 remain unclear. We used transcranial magnetic stimulation (TMS) to examine the cortical encoding of thumb movements in M1 of healthy humans. We performed M1 mapping of the probability of inducing a thumb movement in a particular direction and used low intensity TMS to disturb a voluntary thumb movement in the same direction during a reaction time task. With both techniques we found spatially segregated representations of the direction of TMS-induced thumb movements, thumb flexion and extension being best separated. Furthermore, the cortical regions corresponding to activation of a thumb muscle differ, depending on whether the muscle functions as agonist or as antagonist for flexion or extension. In addition, we found in the reaction time experiment that the direction of a movement is processed in M1 before the muscles participating in it are activated. It thus appears that one of the organizing principles for the human corticospinal motor system is based on a spatially segregated representation of movement directions and that the representation of individual somatic structures, such as the hand muscles, overlap.

The ventro-medial prefrontal cortex: a major link between the autonomic nervous system, regulation of emotion, and stress reactivity?

ABSTRACT: Recent progress in neuroscience revealed diverse regions of the CNS which moderate autonomic and affective responses. The ventro-medial prefrontal cortex (vmPFC) plays a key role in these regulations. There is evidence that vmPFC activity is associated with cardiovascular changes during a motor task that are mediated by parasympathetic activity. Moreover, vmPFC activity makes important contributions to regulations of affective and stressful situations.This review selectively summarizes literature in which vmPFC activation was studied in healthy subjects as well as in patients with affective disorders. The reviewed literature suggests that vmPFC activity plays a pivotal role in biopsychosocial processes of disease. Activity in the vmPFC might link affective disorders, stressful environmental conditions, and immune function.

Fetal ventral mesencephalon of human and rat origin maintained in vitro and transplanted to 6-hydroxydopamine-lesioned rats gives rise to grafts rich in dopaminergic neurons

Free-floating roller tube cultures of human fetal (embryonic age 6-10 weeks post-conception) and rat fetal (embryonic day 13) ventral mesencephalon were prepared. After 7-15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3-5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. D-amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.

Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease

Transplantation of fetal dopaminergic (DA) neurons offers an experimental therapy for Parkinson's disease (PD). The low availability and the poor survival and integration of transplanted cells in the host brain are major obstacles in this approach. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with growth- and survival-promoting capabilities for developing DA neurons. In the present study, we examined whether pretreatment of ventral mesencephalic (VM) free-floating roller tube (FFRT) cultures with GDNF would improve graft survival and function. For that purpose organotypic cultures of E14 rat VM were grown for 2, 4 or 8 days in the absence (control) or presence of GDNF [10 ng/ml] and transplanted into the striatum of 6-hydroxydopamine-lesioned rats. While all groups of rats showed a significant reduction in d-amphetamine-induced rotations at 6 weeks posttransplantation a significantly improved graft function was observed only in the days in vitro (DIV) 4 GDNF pretreated group compared to the control group. In addition, no statistical significant differences between groups were found in the number of surviving tyrosine hydroxylase-immunoreactive (TH-ir) neurons assessed at 9 weeks posttransplantation. However, a tendency for higher TH-ir fiber outgrowth from the transplants in the GDNF pretreated groups as compared to corresponding controls was observed. Furthermore, GDNF pretreatment showed a tendency for a higher number of GIRK2 positive neurons in the grafts. In sum, our findings demonstrate that GDNF pretreatment was not disadvantageous for transplants of embryonic rat VM with the FFRT culture technique but only marginally improved graft survival and function.

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to induce lucid dreaming. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.