Dose-response effect of vibratory stimulus on synaptic and muscle plasticity in a middle-aged murine model

Whole body vibration plays a central role in many work categories and can represent a health risk to the musculoskeletal system and peripheral nervous system. However, studies in animal and human models have shown that vibratory training, experimentally and/or therapeutically induced, can exert beneficial effects on the whole body, as well as improve brain functioning and reduce cognitive decline related to the aging process. Since the effects of vibratory training depend on several factors, such as vibration frequency and vibration exposure time, in this work, we investigated whether the application of three different vibratory protocols could modulate synaptic and muscle plasticity in a middle-aged murine model, counteracting the onset of early symptoms linked to the aging process. To this end, we performed in vitro electrophysiological recordings of the field potential in the CA1 region of mouse hippocampal slices, as well as histomorphometric and ultrastructural analysis of muscle tissue by optic and transmission electron microscopy, respectively. Our results showed that protocols characterized by a low vibration frequency and/or a longer recovery time exert positive effects at both hippocampal and muscular level, and that these effects improve significantly by varying both parameters, with an action comparable with a dose-response effect. Thus, we suggested that vibratory training may be an effective strategy to counteract cognitive impairment, which is already present in the early stages of the aging process, and the onset of sarcopenia, which is closely related to a sedentary lifestyle. Future studies are needed to understand the underlying molecular mechanisms and to determine an optimal vibratory training protocol

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors

Corrigendum: Current drive at plasma densities required for thermonuclear reactors

Nature Communications 1: Article number: 55 (2010); Published: 10 August 2010; Updated:19 September 2013. In Fig. 3 of this Article, the colours of the blue and green curves were accidentally interchanged while the manuscript was being revised. In addition, the x axis labels on Fig. 4 should have read 'Frequency (MHz)'

Entorhinal cortex-subiculum interactions in an experimental model of mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) patients present with seizuresinvolving the limbic system and with a pattern of brain damage characterizedby neuronal loss in CA1/CA3 areas, dentate hilus, and entorhinalcortex (EC), layer III (Houser CR. Adv Neurol 1999;79:743–61). Similarfindings are seen in laboratory animals following pilocarpine injection(Turski WA, et al. Behav Brain Res 1983;9:315–35). This procedure inducesan initial convulsive response, which is followed within 2–3 weeksby recurrent seizures. Limbic network hyperexcitability in MTLE andin animal models results from seizure-induced brain damage leading to(a) synaptic reorganization (Cavazos JE, et al. J Neurosci 1991;11:2795–803; Houser CR. Adv Neurol 1999;79:743–61) and (b) changes inGABAreceptor–mediated inhibition (Buhl EH, et al. Science 1996;271:369–7;Doherty J, Dingledine R. J Neurosci 2001;21:2048–57. However, it isunclear how these changes lead to a chronic epileptic condition.CA3-driven interictal activity induced in normal brain tissue by epileptogenicstimuli inhibits the EC from generating ictal discharges (BarbarosieM, Avoli M. J Neurosci 1997;17:9308–14), suggesting that CA3damage causes a decrease of hippocampal output activity that wouldrelease EC ictogenesis and establish a chronic epileptic condition. Accordingly,slices obtained from pilocarpine-treated epileptic mice respondto 4-aminopyridine (4AP) application by generating (a) CA3-driven interictal activity that is less frequent than in nonepileptic control(NEC) tissue, and (b) ictal discharges that do not disappear overtime and propagate to the CA1-subiculum via the temporoammonic path(D’Antuono M, et al. J Neurophysiol 2002;87:634–9). From these findings,we predicted that limbic seizures result from EC–subiculum interactions.Using brain slices obtained from pilocarpine-treated, epilepticrats, we found that decreased CA3 output function, along with reverberationbetween EC and subiculum networks, lead to in vitro epileptogenesis.First, intense activation of EC and subiculum was identifiedwith intrinsic optical signal (IOS) recordings in pilocarpine-treated, butnot in NEC slices. Second, using field potential recordings during 4APapplication, we established that CA3-driven interictal activity occursat lower frequency in pilocarpine-treated slices and that disconnectionof the EC from the subiculum attenuates 4AP-induced ictal dischargesin pilocarpine-treated, but not in NEC slices. Third, the distributionof FosB/FosB-related proteins in epileptic tissue demonstrated distinctpatterns overlapping those seen with IOS recordings, with the highestintensity in layer III of the lateral EC.In conclusion, our data show that hippocampal damage in epilepticrats, and perhaps in MTLE patients, hampers the ability of CA3 outputactivity to control ictogenesis in the EC. Such a process is reinforced byinteractions between subiculum and EC networks

Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of absence seizures

We used sharp-electrode, intracellular recordings in an in vitro brain slice preparation to study the excitability of neocortical neurons located in the deep layers (> 900 mu m from the pia) of epileptic (180-210-days old) Wistar Albino Glaxo/Rijswijk (WAG/Rij) and age-matched, non-epileptic control (NEC) rats. Wistar Albino Glaxo/Rijswijk rats represent a genetic model of absence seizures associated with generalized spike and wave (SW) discharges in vivo. When filled with neurobiotin, these neurons had a typical pyramidal shape with extensive apical and basal dendritic trees; moreover, WAG/Rij and NEC cells had similar fundamental electrophysiological and repetitive firing properties. Sequences of excitatory postsynaptic potentials (EPSPs) and hyperpolarizing inhibitory postsynaptic potentials (IPSPs) were induced in both the strains by electrical stimuli delivered to the underlying white matter or within the neocortex; however, in 24 of 55 regularly firing WAG/Rij cells but only in 2 of 25 NEC neurons, we identified a late EPSP that (1) led to action potential discharge and (2) was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (20 mu M; n = 8/8 WAG/Rij cells). Finally, we found that the fast and slow components of the stimulus-induced IPSPs recorded during the application of glutamatergic receptor antagonists had similar reversal potentials in the two strains, while the peak conductance of the fast IPSP was significantly reduced in WAG/Rij cells. These findings document an increase in synaptic excitability that is mediated by NMDA receptors, in epileptic WAG/Rij rat neurons located in neocortical deep layers. We propose that this mechanism may be instrumental for initiating and maintaining generalized SW discharges in vivo

Impaired activation of CA3 pyramidal neurons in the epileptic hippocampus

We employed in vitro and ex vivo imaging tools to characterize the function of limbic neuron networks in pilocarpine-treated and age-matched, nonepileptic control (NEC) rats. Pilocarpine-treated animals represent an established model of mesial temporal lobe epilepsy. Intrinsic optical signal (IOS) analysis of hippocampal-entorhinal cortex (EC) slices obtained from epileptic rats 3 wk after pilocarpine-induced status epilepticus (SE) revealed hyperexcitability in many limbic areas, but not in CA3 and medial EC layer III. By visualizing immunopositivity for FosB/Delta FosB-related proteins-which accumulate in the nuclei of neurons activated by seizures-we found that: (1) 24 h after SE, FosB/Delta FosB immunoreactivity was absent in medial EC layer III, but abundant in dentate gyrus, hippocampus proper (including CA3) and subiculum; (2) FosB/Delta FosB levels progressively diminished 3 and 7 d after SE, whereas remaining elevated (p < 0.01) in subiculum; (3) FosB/Delta FosB levels sharply increased 2 wk after SE (and remained elevated up to 3 wk) in dentate gyrus and in most of the other areas but not in CA3. A conspicuous neuronal damage was noticed in medial EC layer III, whereas hippocampus was more preserved. IOS analysis of the stimulus-induced responses in slices 3 wk after SE demonstrated that IOSs in CA3 were lower (p < 0.05) than in NEC slices following dentate gyrus stimulation, but not when stimuli were delivered in CA3. These findings indicate that CA3 networks are hypoactive in comparison with other epileptic limbic areas. We propose that this feature may affect the ability of hippocampal outputs to control epileptiform synchronization in EC