DIY caging apparatus to facilitate chronic and continuous stimulation or recording in an awake rodent

Chronic stimulation of and recording from the brain and brain diseases can require expensive apparatus and tedious cycles of inducing rodents with anesthesia. To resolve this, we have designed and fabricated a low-cost (~$75 vs. $450) DIY rodent caging apparatus consisting of commercially available and 3D-printed components. This apparatus is customizable and can be used to rapidly prototype devices with large rodent sample sizes. Importantly, it enables continuous and chronic stimulation of and recording from the brains of awake and freely moving rodents. It also opens the possibilities of trying complex paradigms of treatment (continuous, intermittent, variable, and chronic). We have successfully used this caging apparatus for chronic intratumoral hypothermia treatment and are currently using it while advancing electrotactic therapies.

Effects of stimulus pulse rate on somatosensory adaptation in the human cortex

BackgroundIntracortical microstimulation (ICMS) of the somatosensory cortex can restore sensation to people with neurological diseases. However, many aspects of ICMS are poorly understood, including the effect of continuous stimulation on percept intensity over time.ObjectiveHere, we evaluate how tactile percepts, evoked by ICMS in the somatosensory cortex of a human participant adapt over time.MethodsWe delivered continuous and intermittent ICMS to the somatosensory cortex and assessed the reported intensity of tactile percepts over time in a human participant. Experiments were conducted across approximately one year and linear mixed effects models were used to assess significance.ResultsContinuous stimulation at high frequencies led to rapid decreases in intensity, while low frequency stimulation maintained percept intensity for longer periods. Burst-modulated stimulation extended the time before the intensity began to decrease, but all protocols ultimately resulted in complete sensation loss within one minute. Intermittent stimulation paradigms with several seconds between stimulus trains also led to decreases in intensity on many electrodes, but never resulted in extinction of sensation after over three minutes of stimulation. Additionally, longer breaks between each pulse train resulted in some recovery of the stimulus-evoked percepts. For several electrodes, intermittent stimulation had almost no effect on the perceived intensity.ConclusionsIntermittent ICMS paradigms were more effective at maintaining percepts, and given that transient activity in the somatosensory cortex dominates the response to object contact, this stimulation method may mimic natural cortical activity and improve the perception of stimulation over time.

Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies

Rab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here, we report the generation and characterization of molecularly defined null mutants for all 26 rab genes in Drosophila. In flies, all rab genes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous system-enriched Rabs yielded viable and fertile flies without obvious morphological defects. However, all 13 mutants differentially affected development when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. We identified a synaptic maintenance defect following continuous stimulation for six mutants, including an autophagy-independent role of rab26. The complete mutant collection generated in this study provides a basis for further comprehensive studies of Rab GTPases during development and function in vivo.

Application of Attachable Magnetic Nerve Stimulator in Intraoperative Facial Nerve Monitoring during Ear Surgery

We developed an attachable magnetic nerve stimulator (AMNS) that connects the metallic instruments to a neurophysiological monitoring unit for monitoring the facial nerve (FN) during ear surgery and present our experiences with intraoperative neuromonitoring (IONM) of the FN using AMNS. The FN in 20 patients who underwent tympanomastoidectomy for chronic ear disease was examined. The electromyography (EMG) amplitudes of the FN using AMNS were assessed. The EMG amplitudes of the FN at 1.00-mA stimulation during drilling were 265 ± 64 µV in the orbicularis oris and 288 ± 57 µV in the orbicularis oculi. The EMG amplitudes using AMNS attached to the surgical instruments under 0.35-mA stimulus at the tympanic segment of the FN were 196 ± 43 µV in the orbicularis oris and 197 ± 41 µV in the orbicularis oculi. The application of continuous stimulation with burr and surgical instruments using the AMNS is feasible and effective for FN stimulation and identification.

Systematic functional analysis of Rab GTPases reveals limits of neuronal robustness in Drosophila

SummaryRab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here we report the generation and characterization of molecularly defined null mutants for all 26 rab genes in Drosophila. In addition, we created a transgenic fly collection for the acute, synchronous release system RUSH for all 26 Rabs. In flies, all rab genes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous-system enriched Rabs yields viable and fertile flies without obvious morphological defects. However, 9 of these 13 affect either developmental timing when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. These defects are non-lethal under laboratory conditions, but represent sensitized genetic backgrounds that reveal limits of developmental and functional robustness to environmental challenges. Interestingly, the neuronal rab26 was previously proposed to function in synaptic maintenance by linking autophagy and synaptic vesicle recycling and we identified rab26 as one of six rab mutants with reduced synaptic function under continuous stimulation conditions. However, we found no changes to autophagy or synaptic vesicle markers in the rab26 mutant, but instead a cell-specific role in membrane receptor turnover associated with cholinergic synapses in the fly visual system. Our systematic functional analyses suggest that several Rabs ensure robust development and function under varying environmental conditions. The mutant and transgenic fly collections generated in this study provide a basis for further studies of Rabs during development and homeostasis in vivo.

Burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia in humans

The aim of the present study was to compare the efficacy of burst-like conditioning electrical stimulation vs. continuous stimulation of cutaneous nociceptors for inducing increased pinprick sensitivity in the surrounding unstimulated skin (a phenomenon referred to as secondary hyperalgesia). In a first experiment ( n = 30), we compared the increase in mechanical pinprick sensitivity induced by 50-Hz burst-like stimulation ( n = 15) vs. 5-Hz continuous stimulation ( n = 15) while maintaining constant the total number of stimuli and the total duration of stimulation. We found a significantly greater increase in mechanical pinprick sensitivity in the surrounding unstimulated skin after 50-Hz burst-like stimulation compared with 5-Hz continuous stimulation ( P = 0.013, Cohen’s d = 0.970). Importantly, to control for the different frequency of stimulation, we compared in a second experiment ( n = 40) 5-Hz continuous stimulation ( n = 20) vs. 5-Hz burst-like stimulation ( n = 20), this time while keeping the total number of stimuli as well as the frequency of stimulation identical. Again, we found a significantly greater increase in pinprick sensitivity after 5-Hz burst-like stimulation compared with 5-Hz continuous stimulation ( P = 0.009, Cohen’s d = 0.868). To conclude, our data indicate that burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia. NEW & NOTEWORTHY Burst-like electrical conditioning stimulation of cutaneous nociceptors is more efficacious than continuous stimulation for inducing heterosynaptic facilitation of mechanical nociceptive input in humans.