Activation of the central nervous system induced by micro-magnetic stimulation

Electrical and transcranial magnetic stimulation have proven to be therapeutically beneficial for patients suffering from neurological disorders. Moreover, these stimulation technologies have provided invaluable tools for investigating nervous system functions. Despite this success, these technologies have technical and practical limitations impeding the maximization of their full clinical and preclinical potential. Recently, micro-magnetic stimulation, which may offer advantages over electrical and transcranial magnetic stimulation, has proven effective in activating the neuronal circuitry of the retina in vitro. Here we demonstrate that this technology is also capable of activating neuronal circuitry on a systems level using an in vivo preparation. Specifically, the application of micro-magnetic fields to the dorsal cochlear nucleus activates inferior colliculus neurons. Additionally, we demonstrate the efficacy and characteristics of activation using different magnetic stimulation parameters. These findings provide a rationale for further exploration of micro-magnetic stimulation as a prospective tool for clinical and preclinical applications

Solenoidal Micromagnetic Stimulation Enables Activation of Axons With Specific Orientation

Electrical stimulation of the central and peripheral nervous systems - such as deep brain stimulation, spinal cord stimulation, and epidural cortical stimulation are common therapeutic options increasingly used to treat a large variety of neurological and psychiatric conditions. Despite their remarkable success, there are limitations which if overcome, could enhance outcomes and potentially reduce common side-effects. Micromagnetic stimulation (μMS) was introduced to address some of these limitations. One of the most remarkable properties is that μMS is theoretically capable of activating neurons with specific axonal orientations. Here, we used computational electromagnetic models of the μMS coils adjacent to neuronal tissue combined with axon cable models to investigate μMS orientation-specific properties. We found a 20-fold reduction in the stimulation threshold of the preferred axonal orientation compared to the orthogonal direction. We also studied the directional specificity of μMS coils by recording the responses evoked in the inferior colliculus of rodents when a pulsed magnetic stimulus was applied to the surface of the dorsal cochlear nucleus. The results confirmed that the neuronal responses were highly sensitive to changes in the μMS coil orientation. Accordingly, our results suggest that μMS has the potential of stimulating target nuclei in the brain without affecting the surrounding white matter tracts

KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients

The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. We further used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington's disease (HD) mouse and human model systems. Surprisingly, we discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. In contrast, selective activation of NRF2 signaling potently repressed the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes. Moreover, in primary monocytes from HD patients and healthy subjects, NRF2 induction repressed expression of the proinflammatory cytokines IL-1, IL-6, IL-8, and TNFα. Together, our results demonstrate a multifaceted protective potential of NRF2 signaling in key cell types relevant to HD pathology

Induction of enhanced acoustic startle response by noise exposure: dependence on exposure conditions and testing parameters and possible relevance to hyperacusis.

There has been a recent surge of interest in the development of animal models of hyperacusis, a condition in which tolerance to sounds of moderate and high intensities is diminished. The reasons for this decreased tolerance are likely multifactorial, but some major factors that contribute to hyperacusis are increased loudness perception and heightened sensitivity and/or responsiveness to sound. Increased sound sensitivity is a symptom that sometimes develops in human subjects after acoustic insult and has recently been demonstrated in animals as evidenced by enhancement of the acoustic startle reflex following acoustic over-exposure. However, different laboratories have obtained conflicting results in this regard, with some studies reporting enhanced startle, others reporting weakened startle, and still others reporting little, if any, change in the amplitude of the acoustic startle reflex following noise exposure. In an effort to gain insight into these discrepancies, we conducted measures of acoustic startle responses (ASR) in animals exposed to different levels of sound, and repeated such measures on consecutive days using a range of different startle stimuli. Since many studies combine measures of acoustic startle with measures of gap detection, we also tested ASR in two different acoustic contexts, one in which the startle amplitudes were tested in isolation, the other in which startle amplitudes were measured in the context of the gap detection test. The results reveal that the emergence of chronic hyperacusis-like enhancements of startle following noise exposure is highly reproducible but is dependent on the post-exposure thresholds, the time when the measures are performed and the context in which the ASR measures are obtained. These findings could explain many of the discrepancies that exist across studies and suggest guidelines for inducing in animals enhancements of the startle reflex that may be related to hyperacusis

Report of the turnip aphid, Lipaphis erysimi (Kaltenbach, 1843) from Missouri, USA

The turnip aphid, Lipaphis erysimi (Kaltenbach, 1843), is one of the most destructive pests in the United States. It has been reported in 33 states, but had not been reported in the state of Missouri. In this study we report this species for the first time in Missouri

Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure

Abstract Previous studies have shown that the dorsal cochlear nucleus exhibits increased spontaneous activity after exposure to intense sound. Such increases were apparent 1^2 months after the exposure and were generally proportional to the shift in response thresholds induced by the same exposure. The purpose of the present study was to determine whether this sound-induced increase in spontaneous activity is an early event which can be observed shortly after exposure. As in previous studies, anesthetized hamsters ranging in postnatal age from 60^70 days were exposed to a 10-kHz tone at levels between 125 and 130 dB SPL for a period of 4 h. Control animals were similarly anesthetized but were not exposed to the intense tone. Exposed animals were examined in two groups, one at 30 days after exposure, the other at 2 days after exposure. Time of exposure was adjusted so that all animals were between 90 and 100 days of age when spontaneous activity was studied electrophysiologically. The results showed that the increases in spontaneous activity, which were evident at 30 days after exposure, were not observed in animals studied 2 days after exposure. This result contrasted with the effect of the intense tone exposure on neural response thresholds. That is, the shifts in response thresholds seen 2 days after exposure were similar to those observed in animals studied 30 days after exposure. These results indicate that changes in spontaneous activity reflect a more slowly developing phenomenon and occur secondarily after induction of threshold shift. z 1998 Elsevier Science B.V. All rights reserved

Dependence of enhancement of startle on threshold.

<p>The histogram depicts maximal ASR amplitudes with respect to thresholds for exposed animals. The dashed red line represents the mean maximal startle amplitude of control animals (thresholds for these animals ranged from 18 to 33 dB SPL). A–E: Representative ASR growth curves of exposed animals with different thresholds. When thresholds were less than 50 dB, startle amplitudes were similar to those of controls. For animals with thresholds of 50–70 dB, enhancements of startle were clearly apparent, but for animals with thresholds above 70 dB SPL, ASR amplitudes were in most cases reduced below control levels.</p