Postnatal development of electrophysiological and morphological properties in layer 2/3 and layer 5 pyramidal neurons in the mouse primary visual cortex.

Eye-opening is a critical point for laminar maturation of pyramidal neurons (PNs) in primary visual cortex. Knowing both the intrinsic properties and morphology of PNs from the visual cortex during development is crucial to contextualize the integration of visual inputs at different age stages. Few studies have reported changes in intrinsic excitability in these neurons but were restricted to only one layer or one stage of cortical development. Here, we used in vitro whole-cell patch-clamp to investigate the developmental impact on electrophysiological properties of layer 2/3 and layer 5 PNs in mouse visual cortex. Additionally, we evaluated the morphological changes before and after eye-opening and compared these in adult mice. Overall, we found a decrease in intrinsic excitability in both layers after eye-opening which remained stable between juvenile and adult mice. The basal dendritic length increased in layer 5 neurons, whereas spine density increased in layer 2/3 neurons after eye-opening. These data show increased number of synapses after onset of sensory input paralleled with a reduced excitability, presumably as homeostatic mechanism. Altogether, we provide a database of the properties of PNs in mouse visual cortex by considering the layer- and time-specific changes of these neurons during sensory development.

Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Electrophysiological properties of layer 2/3 pyramidal neurons in the primary visual cortex of a retinitis pigmentosa mouse model (rd10).

Retinal degeneration is one of the main causes of visual impairment and blindness. One group of retinal degenerative diseases, leading to the loss of photoreceptors, is collectively termed retinitis pigmentosa. In this group of diseases, the remaining retina is largely spared from initial cell death making retinal ganglion cells an interesting target for vision restoration methods. However, it is unknown how downstream brain areas, in particular the visual cortex, are affected by the progression of blindness. Visual deprivation studies have shown dramatic changes in the electrophysiological properties of visual cortex neurons, but changes on a cellular level in retinitis pigmentosa have not been investigated yet. Therefore, we used the rd10 mouse model to perform patch-clamp recordings of pyramidal neurons in layer 2/3 of the primary visual cortex to screen for potential changes in electrophysiological properties resulting from retinal degeneration. Compared to wild-type C57BL/6 mice, we only found an increase in intrinsic excitability around the time point of maximal retinal degeneration. In addition, we saw an increase in the current amplitude of spontaneous putative inhibitory events after a longer progression of retinal degeneration. However, we did not observe a long-lasting shift in excitability after prolonged retinal degeneration. Together, our results provide evidence of an intact visual cortex with promising potential for future therapeutic strategies to restore vision.

Clinical significance of contact lens related changes of ocular surface tissue observed on optical coherence images.

PURPOSE: To investigate the relationship between the real contact lens imprint into the conjunctival tissue, observed by optical coherence tomography (OCT) and conjunctival staining and contact lens wearing comfort. METHODS: 17 participants (mean age = 26.6 SD ± 3.6 years; 7 females) were fitted with three different contact lenses base curves of the same silicone hydrogel custom lens type (Visell 50; Hecht Contactlinsen, Au, Germany) in a randomised order. One lens was optimally fitted according to the manufacturer's recommendation, one fitted 0.4 mm flatter and one fitted 0.4 mm steeper. After 4 h of lens wear the contact lens edge in the area of the conjunctiva was imaged nasally and temporally using OCT (Optovue iVue SD-OCT). To correct the artefact due to optical distortion with OCT, the imprint of all worn lenses was measured on a glass plate afterwards. Conjunctival staining in the limbal region after 4 h of lens wear was classified using the CCLRU Grading Scale. Comfort scoring was based on visual analog scales from 0 (very poor) to 100 (excellent). RESULTS: The mean conjunctival imprint of all contact lens edges was 32.0 ± 8.1 µm before and 7.3 ± 6.5 µm after distortion correction of the OCT images. The distortion corrected conjunctival imprint with the 0.4 mm steeper lens (11.5 ± 6.2 µm) was statistically significantly greater compared to the optimally fitted lens (6.5 ± 5.9 µm) (One-way ANOVA followed Tukey-test; p = 0.017) and greater compared to the 0.4 mm flatter lens (3.9 ± 5.3 µm) (p < 0.001). There was no statistically significant difference between the optimally fitted lens and the 0.4 mm flatter lens (p = 0.209). The nasally measured imprint (11.4 ± 9.0 µm) was significantly greater than the temporally measured (3.3 ± 7.6 µm) (p < 0.001). There was no statistically significant correlation between the amount of conjunctival imprint and the graded conjunctival staining (p = 0.346) or the wearer's comfort (p = 0.735). CONCLUSIONS: Contact lens edges imaged by OCT exhibited displacement artefacts. The observed conjunctival imprints are a combination of real conjunctival compression and artefacts. A deeper imprint of the contact lens into the conjunctiva caused by a steeper base curve was not related to clinically significant staining or changes in comfort after 4 h of lens wear. The observed differences between nasal and temporal imprint are likely to be caused by variations of conjunctival thickness and the shape of the underlying sclera.