Objective. The restoration of vision in blind patients suffering from degenerative retinal diseases like retinitis pigmentosa may be obtained by local electrical stimulation with retinal implants. In this study, a very large electrode array for retinal stimulation (VLARS) was introduced and tested regarding its safety in implantation and biocompatibility. Further, the array’s stimulation capabilities were tested in an acute setting. Approach. The polyimide-based implants have a diameter of 12 mm, cover approximately 110 mm2 of the retinal surface and carrying 250 iridium oxide coated gold electrodes. The implantation surgery was established in cadaveric porcine eyes. To analyze biocompatibility, ten rabbits were implanted with the VLARS device, and observed for 12 weeks using slit lamp examination, fundus photography, optical coherence tomography (OCT) as well as ultrasound imaging. After enucleation, histological examinations were performed. In acute stimulation experiments, electrodes recorded cortical field potentials upon retinal stimulation in the visual cortex in rabbits. Main results. Implantation studies in rabbits showed that the implantation surgery is safe but difficult. Retinal detachment induced by retinal tears was observed in five animals in varying severity. In five cases, corneal edema reduced the quality of the follow-up examinations. Findings in OCT-imaging and funduscopy suggested that peripheral fixation was insufficient in various animals. Results of the acute stimulation demonstrated the array’s ability to elicit cortical responses. Significance. Overall, it was possible to implant very large epiretinal arrays. On retinal stimulation with the VLARS responses in the visual cortex were recorded. The VLARS device offers the opportunity to restore a much larger field of visual perception when compared to current available retinal implants.

Schizophrenic patients show altered sensory perception as well as changes in electrical and magnetic brain responses to sustained, frequency-modulated sensory stimulation. Both the amplitude and temporal precision of the neural responses differ in patients as compared to control subjects, and these changes are most pronounced for stimulation at gamma frequencies (20–40 Hz). In addition, patients display enhanced spontaneous gamma oscillations, which has been interpreted as ‘neural noise’ that may interfere with normal stimulus processing. To investigate electrophysiological markers of aberrant sensory processing in a model of schizophrenia, we recorded neuronal activity in primary somatosensory cortex of mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1. Sensory responses to sustained 20–70 Hz whisker stimulation were analyzed with respect to firing rates, spike precision (phase locking) and gamma oscillations, and compared to baseline conditions. The mutants displayed elevated spontaneous firing rates, a reduced gain in sensory-evoked spiking and gamma activity, and reduced spike precision of 20–40 Hz responses. These findings present the first in vivo evidence of the linkage between a genetic marker and altered stimulus encoding, thus suggesting a novel electrophysiological endophenotype of schizophrenia.

Sparse population activity is a well-known feature of supragranular sensory neurons in neocortex. The mechanisms underlying sparseness are not well understood because a direct link between the neurons activated in vivo, and their cellular properties investigated in vitro has been missing. We used two-photon calcium imaging to identify a subset of neurons in layer L2/3 (L2/3) of mouse primary somatosensory cortex that are highly active following principal whisker vibrotactile stimulation. These high responders (HRs) were then tagged using photoconvertible green fluorescent protein for subsequent targeting in the brain slice using intracellular patch-clamp recordings and biocytin staining. This approach allowed us to investigate the structural and functional properties of HRs that distinguish them from less active control cells. Compared to less responsive L2/3 neurons, HRs displayed increased levels of stimulus-evoked and spontaneous activity, elevated noise and spontaneous pairwise correlations, and stronger coupling to the population response. Intrinsic excitability was reduced in HRs, while we found no evidence for differences in other electrophysiological and morphological parameters. Thus, the choice of which neurons participate in stimulus encoding may be determined largely by network connectivity rather than by cellular structure and function.

To reveal the neuronal underpinnings of sensory processing deficits in patients with schizophrenia, previous studies have investigated brain activity in response to sustained sensory stimulation at various frequencies. This paradigm evoked neural activity at the stimulation frequency and harmonics thereof. During visual and auditory stimulation that elicited enhanced or ‘resonant’ responses in healthy controls, patients with schizophrenia displayed reduced activity. The present study sought to elucidate the cellular basis of disease-related deficits in sensory resonance properties using mice heterozygous for the schizophrenia susceptibility gene Neuregulin 1 (NRG1). We applied repetitive whisker stimulation at 1–15 Hz, a range relevant to whisking behavior in mice, and measured cellular activity in the primary somatosensory cortex. At frequencies where control mice displayed enhancements in measures of response magnitude and precision, NRG1 (+/−) mutants showed reductions. Our results demonstrate for the first time a link between a mutation of a schizophrenia risk gene and altered neuronal resonance properties in sensory cortex.