Adult-born neurons continuously incorporate into the olfactory bulb where they rapidly establish contacts with a variety of synaptic inputs. Little is known, however, about the functional properties of their output. Characterization of synaptic outputs from new neurons is essential to assess the functional impact of adult neurogenesis on mature circuits. Here, we used optogenetics to control neurotransmitter release from new neurons. We found that light-induced synaptic GABA release from adult-born neurons leads to profound modifications of postsynaptic target firing patterns. We revealed that functional output synapses form just after new cells acquire the faculty to spike, but most synapses were made a month later. Despite discrepancies in the timing of new synapse recruitment, the properties of postsynaptic signals remain constant. Remarkably, we found that all major cell types of the olfactory bulb circuit, including output neurons and several distinct subtypes of local interneurons, were contacted by adult-born neurons. Thus, this study provides new insights into how new neurons integrate into the adult neural network and may influence the sense of smell.

Purpose: To compare the performance of Tecnis Eyhance ICB00 with Tecnis PCB00 IOL for far, intermediate, and near vision, in patients after bilateral cataract surgery. Settings: This study was done at Geneva University Hospitals. Design: This is a retrospective study of 224 eyes that underwent cataract between May 2019 and June 2020. Methods: Visual acuity was assessed from month 1 to 12 after surgery for distance, intermediate and near visual acuity, by the same optometrist, which was blind regarding the type of IOL. The patients answered to a quality of life questionnaire. Patients were excluded for: monocular surgery, macular disease, other IOL type, or inability to reach 20/20 visual acuity in both eyes without correction. Results: One hundred and fifty-two eyes were excluded. Three groups were then analyzed: PCB00 group (38 eyes), ICB00 group (22 eyes), and mismatch group (12 eyes). Monocular visual acuities (CIVA, UNVA and CNVA, in logMAR) were higher in the ICB00 group than the PCB00 group (respectively 0.3 vs 0.4, p = 0.0033; 0.3 vs 0.4, p = 0.0408; 0.3 vs 0.4, p = 0.0039). Binocular visual acuities, CIVA and CNVA were higher in the ICB00 group than the PCB00 group (0.2 vs 0.4, p = 0.0061; 0.15 vs 0.3, p = 0.018). This mirrored the findings of the quality of life questionnaire. There was no significant difference between PCB00 and mismatch groups. Conclusions: the Tecnis Eyhance was more effective for intermediate and near vision. The central defocus of the lens might help patients achieve spectacle independence and better quality of life.

Neuronal activity modulates the membrane diffusion of postsynaptic γ-aminobutyric acid (GABA)_A receptors (GABA_ARs), thereby regulating the efficacy of GABAergic synapses. The K289M mutation in GABA_ARs subunit γ2 has been associated with the generalized epilepsy with febrile seizures plus (GEFS+) syndrome. This mutation accelerates receptor deactivation and therefore reduces inhibitory synaptic transmission. Yet, it is not clear why this mutation specifically promotes febrile seizures. We show that upon raising temperature both the number of GABA_ARs clusters and the frequency of miniature inhibitory postsynaptic currents decreased in neurons expressing the K289M mutant but not wild-type (WT) recombinant γ2. Single-particle tracking experiments revealed that raising temperature increases the membrane diffusion of synaptic GABA_ARs containing the K289M mutant but not WT recombinant γ2. This effect was mediated by enhanced neuronal activity as it was blocked by glutamate receptor antagonists and was mimicked by the convulsant 4-aminopyridine. Our data suggest the K289M mutation in γ2 confers GABA_ARs with enhanced sensitivity of their membrane diffusion to neuronal activity. Enhanced activity during hyperthermia may then trigger the escape of receptors from synapses and thereby further reduce the efficacy of GABAergic inhibition. Alteration of the membrane diffusion of neurotransmitter receptors therefore represents a new mechanism in human epilepsy.

The Fundus photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) studies showed that ED providers poorly recognized funduscopic findings in patients in the ED. We tested a modified version of the Brain and Optic Nerve Study Artificial Intelligence (BONSAI) deep learning system on nonmydriatic fundus photographs from the FOTO-ED studies to determine if the deep learning system could have improved the detection of papilledema had it been available to ED providers as a real-time diagnostic aid. Retrospective secondary analysis of a cohort of patients included in the FOTO-ED studies. The testing data set included 1608 photographs obtained from 828 patients in the FOTO-ED studies. Photographs were reclassified according to the optic disc classification system used by the deep learning system ("normal optic discs," "papilledema," and "other optic disc abnormalities"). The system's performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 1-vs-rest strategy, with reference to expert neuro-ophthalmologists. The BONSAI deep learning system successfully distinguished normal from abnormal optic discs (AUC 0.92 [95% confidence interval {CI} 0.90-0.93]; sensitivity 75.6% [73.7%-77.5%] and specificity 89.6% [86.3%-92.8%]), and papilledema from normal and others (AUC 0.97 [0.95-0.99]; sensitivity 84.0% [75.0%-92.6%] and specificity 98.9% [98.5%-99.4%]). Six patients with missed papilledema in 1 eye were correctly identified by the deep learning system as having papilledema in the other eye. The BONSAI deep learning system was able to reliably identify papilledema and normal optic discs on nonmydriatic photographs obtained in the FOTO-ED studies. Our deep learning system has excellent potential as a diagnostic aid in EDs and non-ophthalmology clinics equipped with nonmydriatic fundus cameras. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.