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Scleral buckling is a highly successful technique for the repair of rhegmatogenous retinal detachment that requires intra-operative examination of the retina and treatment of retinal breaks via indirect ophthalmoscopy. Data suggest that scleral buckling likely results in improved outcomes for many patients but is declining in popularity, perhaps because of significant advances in vitrectomy instrumentation and visualization systems. Emerging data suggest that chandelier-assisted scleral buckling is safe and has many potential advantages over traditional buckling techniques. By combining traditional scleral buckling with contemporary vitreoretinal visualization techniques, chandelier-assistance may increase the popularity of scleral buckling to treat primary rhegmatogenous retinal detachment for surgeons of the next generation, maintaining buckling as an option for appropriate patients in the future.

Purpose To compare the surgical results in cases of primary rhegmatogenous retinal detachments between standard scleral buckling (SSB) and scleral buckling with chandelier illumination (SBC) and to analyse the differences in SBC surgical results between an experienced ophthalmologist and inexperienced ophthalmologists. Methods Consecutive surgical case series of 155 eyes that underwent scleral buckling were retrospectively reviewed and divided into four groups: SSB performed by an experienced ophthalmologist ( n  = 54), SBC performed by an experienced ophthalmologist ( n  = 52), SBC performed by inexperienced ophthalmologists ( n  = 40) and SSB performed by inexperienced ophthalmologists ( n  = 9). Then, these four groups were compared. Results No significant differences were observed between SSB and SBC procedures both performed by the experienced ophthalmologist with regard to demographics, preoperative findings, contents of the surgery, intraoperative complications, retinal reattachment, postoperative findings and postoperative complications. Between SBC performed by the experienced ophthalmologist and SBC performed by the inexperienced ophthalmologists, no significant differences were found regarding intraoperative complications, retinal reattachment, postoperative findings and postoperative complications. Between SSB and SBC procedures both performed by the inexperienced ophthalmologist, a significant difference was found regarding intraoperative complications. Conclusion There were no significant differences in surgical results between SSB and SBC when both were performed by the experienced ophthalmologist. In addition, the surgical results were equal between the experienced ophthalmologist and the inexperienced ophthalmologist as far as SBC was concerned. Learning scleral buckling skills by using SBC is a reasonable course of action for inexperienced ophthalmologists.

Microglia have emerged as critical regulators of synapse development and circuit formation in the healthy brain. To date, examination of microglia in such processes has largely been focused on excitatory synapses. Their roles, however, in the modulation of GABAergic interneuron synapses—particularly those targeting the axon initial segment (AIS)—during development remain enigmatic. Here, we identify a synaptogenic/growth-promoting role for microglia in regulating pyramidal neuron (PyN) AIS synapse formation by chandelier cells (ChCs), a unique interneuron subtype whose axonal terminals, called cartridges, selectively target the AIS. We show that a subset of microglia contacts PyN AISs and ChC cartridges and that such tripartite interactions, which rely on the unique AIS cytoskeleton and microglial GABAB1 receptors, are associated with increased ChC cartridge length and bouton number and AIS synaptogenesis. Conversely, microglia depletion or disease-induced aberrant microglia activation impairs the proper development and maintenance of ChC cartridges and boutons, as well as AIS synaptogenesis. These findings unveil key roles for homeostatic, AIS-associated microglia in regulating proper ChC axonal morphogenesis and synaptic connectivity in the neocortex.

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.

Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.

Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to “depression-like” behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.

Scleral buckling (SB) remains an important technique to master for those interested in treating rhegmatogenous retinal detachment (RRD). Several ways to repair RRD include pneumatic retinopexy (PR), pars plana vitrectomy (PPV), SB or a combination of these. There is a growing worldwide trend that favors PPV as the preferred method for retinal reattachment of primary uncomplicated RRD. Reimbursement issues, operating room access, and technological advances in PPV that improve retinal visualization and less exposure to SB during fellowship training may explain this trend. As the number of SB cases decreases over time, there is a risk that SB becomes a dying art and surgeons in training may not be trained in SB. SB is preferred in eyes with no posterior vitreous detachment and retinal dialysis. SB with minimal gas vitrectomy may be indicated for eyes with inferior pathology. Non-contact wide-angled visualization with chandelier assisted SB may be well suited for teaching new generations of aspiring vitreoretinal surgeons. Its functional and anatomic results compare favorably with conventional SB for primary uncomplicated primary RRD. The main advantage of this technique is the improved visualization even through small pupils. Better visualization ensures treatment of all breaks while avoiding complications during drainage of subretinal fluid and a safer placement of intrascleral sutures for scleral fixation of the buckling element. Recordings of the procedure are easily performed, allowing the surgeons involved to review the case and learn from it. The main disadvantage is the cost involved with the chandelier and the need to have a microscope or a 3D system with a wide angle viewing system. Photoreceptor re-alignment following retinal re-attachment is an important determinant of the post-operative functional outcomes. Different methods of retinal re-attachment apparently result in different degrees of photoreceptor re-alignment. SB may hold an advantage over PPV in this regard. Keywords: rhegmatogenous retinal detachment, chandelier assisted scleral buckling, wide-angled illumination assisted scleral buckling, scleral buckling, pars plana vitrectomy, photoreceptor integrity

The axon initial segment (AIS) is a structure at the start of the axon with a high density of sodium and potassium channels that defines the site of action potential generation. It has recently been shown that this structure is plastic and can change its position along the axon, as well as its length, in a homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory nucleus lead to a lengthening of the AIS and an increase in neuronal excitability. On the other hand, a long-term increase in activity in dissociated rat hippocampal neurons results in an outward movement of the AIS and a decrease in the cell’s excitability. Here, we investigated whether the AIS is capable of undergoing structural plasticity in rat hippocampal organotypic slices, which retain the diversity of neuronal cell types present at postnatal ages, including chandelier cells. These interneurons exclusively target the AIS of pyramidal neurons and form rows of presynaptic boutons along them. Stimulating individual CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components of the axo-axonic synapses did not change position after AIS relocation. We used computational modeling to explore the functional consequences of this partial mismatch and found that it allows the GABAergic synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability. We propose that this spatial arrangement is the optimal configuration for a homeostatic response to long-term stimulation.

Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modeling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.

Although studies have reported various patterns of atherosclerotic aortic plaques (AAPs) detected by non-obstructive aortic angioscopy (NOA), the long-term outcomes associated with AAPs such as puff-chandelier rupture atheromatous plaque (PCR), remain unclear. This study investigated the long-term prognostic significance of AAPs detected by NOA in patients who underwent percutaneous coronary intervention (PCI). This retrospective multicenter cohort study included 167 patients who underwent PCI and NOA. The association between AAPs and the incidence of major adverse cardiac events (MACE) were assessed. MACE was categorized into: MACE1, including cardiac death, myocardial infarction, stroke, and ischemia-driven unplanned revascularization; and MACE2, including cardiac death, myocardial infarction, and stroke. There were no NOA-related complications. Of all AAPs, only PCR showed a significant prognostic value during the follow-up period (mean follow-up period: 6.3 years [range 5.9–6.6]). In multivariable Cox proportional hazards analysis, PCR was an independent predictor of MACE (MACE1; HR 1.91, 95% CI 1.04–3.49, P = 0.04, MACE2; hazard ratio [HR] 4.52, 95% confidence interval [CI] 1.23–16.57, P = 0.02). Kaplan–Meier analysis revealed that PCR was significantly associated with MACE. NOA during PCI is safe and feasible. Detecting PCR by NOA may provide reliable information for identifying patients at high risk of subsequent long-term adverse events after PCI.