Journal of Neurophysiology
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Published By American Physiological Society

1522-1598, 0022-3077

Author(s):  
Line Sofie Loken ◽  
Helena Backlund Wasling ◽  
Håkan Olausson ◽  
Francis McGlone ◽  
Johan Wessberg

Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (n=27), radial (n=8) and peroneal nerves (n=4). Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.


Author(s):  
Rosa Hugosdottir ◽  
Mindy Kasting ◽  
Carsten Dahl Mørch ◽  
Ole Kæseler Andersen ◽  
Lars Arendt-Nielsen

Heat/capsaicin sensitization and electrical high frequency stimulation (HFS) are well known model of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45 °C heat stimulation for 5 min followed by a topical capsaicin patch (4x4 cm) for 30 minutes on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS+HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS) and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pinprick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pinprick stimulation (difference from baseline and control area) was observed in the HFS+HEAT/CAPS session than in the HFS session 20 and 30 minutes after HFS. Furthermore, sensitivity was increased after HFS+HEAT/CAPS compared to after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central- and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.


Author(s):  
Julien Rossato ◽  
Kylie J. Tucker ◽  
Simon Avrillon ◽  
Lilian Lacourpaille ◽  
Ales Holobar ◽  
...  

This study aimed to determine whether neural drive is redistributed between muscles during a fatiguing isometric contraction, and if so, whether the initial level of common synaptic input between these muscles constrains this redistribution. We studied two muscle groups: triceps surae (14 participants) and quadriceps (15 participants). Participants performed a series of submaximal isometric contractions and a torque-matched contraction maintained until task failure. We used high-density surface electromyography to identify the behavior of 1874 motor units from the soleus, gastrocnemius medialis (GM), gastrocnemius lateralis(GL), rectus femoris, vastus lateralis (VL), and vastus medialis(VM). We assessed the level of common drive between muscles in absence of fatigue using a coherence analysis. We also assessed the redistribution of neural drive between muscles during the fatiguing contraction through the correlation between their cumulative spike trains (index of neural drive). The level of common drive between VL and VM was significantly higher than that observed for the other muscle pairs, including GL-GM. The level of common drive increased during the fatiguing contraction, but the differences between muscle pairs persisted. We also observed a strong positive correlation of neural drive between VL and VM during the fatiguing contraction (r=0.82). This was not observed for the other muscle pairs, including GL-GM, which exhibited differential changes in neural drive. These results suggest that less common synaptic input between muscles allows for more flexible coordination strategies during a fatiguing task, i.e., differential changes in neural drive across muscles. The role of this flexibility on performance remains to be elucidated.


Author(s):  
Jie Zhang ◽  
Linlin Li ◽  
Fangwei Xiu

Diabetic retinopathy (DR) is the most common micro-vascular complication of diabetes, and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds respectively in the stimulation of high glucose (HG), to screen for the potential candidate drug. Streptozotocin (STZ)- induced diabetic mice were injected with different doses of the candidate Sesamin every two days for one month. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1β and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. Additionally, Sesamin alleviated brain-retinal barrier breakdown by Evan's blue leakage assay and reduced inflammation in Streptozotocin-induced diabetic mice. In conclusion, Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that Sesamin might serve as a candidate drug for DR treatment.


Author(s):  
Lenneke Kiefer ◽  
Lisa Koch ◽  
Melisa Merdan-Desik ◽  
Bernhard H. Gaese ◽  
Manuela Nowotny

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure. Auditory brainstem responses (ABRs) were measured before, during and up to eight weeks after noise exposure for threshold determination and ABR waveform analysis. Trauma induction with stepwise increasing sound pressure level was interrupted by five interspersed ABR measurements. Comparing short- and long-term dynamics underlying the following noise-induced hearing loss revealed diverging time courses between the three species. Hearing loss occurred early on during noise exposure in all three rodent species at or above trauma frequency. Initial noise level (105 dB SPL) was most effective in rats while the delayed level-increase to 115 dB SPL affected mice much stronger. Induced temporary threshold shifts in rats and mice were larger in animals with lower pre-trauma ABR thresholds. The increase in activity (gain) along the auditory pathway was derived by comparing the amplitudes of short- and long-latency ABR waveform components. Directly after trauma, significant effects were found for rats (decreasing gain) and mice (increasing gain) while gerbils revealed high individual variability in gain changes. Taken together, our comparative study revealed pronounced species-specific differences in the development of noise-induced hearing loss and the related processing along the auditory pathway.


Author(s):  
Qian Li ◽  
Mingwei Qu ◽  
Ningning Wang ◽  
Limin Wang ◽  
Guimei Fan ◽  
...  

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.


Author(s):  
Sunyoung Park ◽  
John T. Serences

Top-down spatial attention enhances cortical representations of behaviorally relevant visual information and increases the precision of perceptual reports. However, little is known about the relative precision of top-down attentional modulations in different visual areas, especially compared to the highly precise stimulus-driven responses that are observed in early visual cortex. For example, the precision of attentional modulations in early visual areas may be limited by the relatively coarse spatial selectivity and the anatomical connectivity of the areas in prefrontal cortex that generate and relay the top-down signals. Here, we used fMRI and human participants to assess the precision of bottom-up spatial representations evoked by high contrast stimuli across the visual hierarchy. Then, we examined the relative precision of top-down attentional modulations in the absence of spatially-specific bottom-up drive. While V1 showed the largest relative difference between the precision of top-down attentional modulations and the precision of bottom-up modulations, mid-level areas such as V4 showed relatively smaller differences between the precision of top-down and bottom-up modulations. Overall, this interaction between visual areas (e.g. V1 vs V4) and the relative precision of top-down and bottom-up modulations suggests that the precision of top-down attentional modulations is limited by the representational fidelity of areas that generate and relay top-down feedback signals.


Author(s):  
Katie H Long ◽  
Kristine R McLellan ◽  
Maria Boyarinova ◽  
Sliman J Bensmaia

Hand proprioception - the sense of the posture and movements of the wrist and digits - is critical to dexterous manual behavior and to stereognosis, the ability to sense the three-dimensional structure of objects held in the hand. To better understand this sensory modality and its role in hand function, we sought to characterize the acuity with which the postures and movements of finger joints are sensed. To this end, we measured the ability of human subjects to discriminate changes in posture and speed around the three joints of the index finger. In these experiments, we isolated the sensory component by imposing the postures on an otherwise still hand, to complement other studies, in which subjects made judgments on actively achieved postures. We found that subjects could reliably sense 12-16% changes in joint angle and 18-32% changes in joint speed. Furthermore, the acuity for posture and speed was comparable across the three joints of the finger. Finally, task performance was unaffected by the presence of a vibratory stimulus, calling into question the role of cutaneous cues in hand proprioception.


Author(s):  
Olivier D. Laflamme ◽  
Marwan Ibrahim ◽  
Turgay Akay

Motor responses in one leg to sensory stimulation of the contralateral leg have been named "crossed reflexes" and extensively investigated in cats and humans. Despite this effort, a circuit-level understanding of the crossed reflexes has remained missing. In mice, advances in molecular genetics enabled insights into the "commissural spinal circuitry" that ensures coordinated leg movements during locomotion. Despite some common features between the commissural spinal circuitry and the circuit for the crossed reflexes, the degree to which they overlap has remained obscure. Here, we describe excitatory crossed reflex responses elicited by electrically stimulating the common peroneal nerve that mainly innervate ankle flexor muscles and the skin on antero-lateral aspect of the hind leg. Stimulation of the peroneal nerve with low current intensity evoked low amplitude motor responses in the contralateral flexor and extensor muscles. At higher current strengths, stimulation of the same nerve evoked stronger and more synchronous responses in the same contralateral muscles. In addition to the excitatory crossed reflex pathway indicated by muscle activation, we demonstrate the presence of an inhibitory crossed reflex pathway, which was modulated when the motor pools were active during walking. The results are compared with the crossed reflex responses initiated by stimulating proprioceptors from extensor muscles and cutaneous afferents from the posterior part of the leg. We anticipate that these findings will be essential for future research combining the in vivo experiments presented here with mouse genetics to understand crossed reflex pathways at the network level in vivo.


Author(s):  
James Edward Niemeyer

Epilepsy is often labelled a network disorder, though a common view of seizures holds that they initiate in a singular onset zone before expanding contiguously outward. A recent report by Choy et al. (2021) leverages new tools to study whole-brain dynamics during epileptic seizures originating in the hippocampus. Cell-type-specific kindling and functional imaging revealed how various brain regions were recruited to seizures and uncovered a novel form of migrating seizure core.


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