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Frontal eye field (FEF) is a key part of oculomotor system, with dominant responses to the direction of single saccades. However, whether and how FEF contributes to sequential saccades remain largely unknown. Here by training rhesus monkeys to perform sequential saccades and recording the neuronal activities in FEF, we found that the sequence-related activities are clearly represented in FEF, and many neurons’ selectivity to saccade direction undergoes dynamic changes during sequential task. In addition, the sequence-related activities are context-dependent, with different firing activities during memory- versus visually-guided sequence. Supra-threshold microstimulation in FEF evokes saccade without altering the overall sequence structure. Pharmacological inactivation of FEF severely impaired the monkey’s performance of sequential saccades, with different effects on the same actions at different positions within the sequence. These results reveal the context-dependent dynamic encoding of saccade direction in FEF, and underscore a critical role of FEF in planning and execution of sequential saccades.In BriefJia, Puyang et al. employed in vivo recording to reveal the dynamic encoding of sequential saccades in primate frontal eye field (FEF), then used electric microstimulation and reversible inactivation to demonstrate the causal role of FEF in controlling saccade sequences.HighlightsFEF neurons respond differently during sequential vs. single saccadesSequence-related FEF activity is context-dependentFEF microstimulation induced saccade without altering sequence structureFEF inactivation severely impaired the performance of sequential saccades

In optic neuropathies, the progressive deterioration of retinal ganglion cell (RGC) function leads to irreversible vision loss. Increasing experimental evidence suggests differing susceptibility for RGC functional subtypes. Here with multi-electrode array recordings, RGC functional loss was characterized at multiple time points in a mouse model of optic nerve crush. Firing rate, latency of response and receptive field size were analyzed for ON, OFF and ON-OFF RGCs separately. It was observed that responses and receptive fields of OFF cells were impaired earlier than ON cells after the injury. For the ON-OFF cells, the OFF component of response was also more susceptible to optic nerve injury than the ON component. Moreover, more ON transient cells survived than ON sustained cells post the crush, implying a diversified vulnerability for ON cells. Together, these data support the contention that RGCs' functional degeneration in optic nerve injury is subtype dependent, a fact that needs to be considered when developing treatments of glaucomatous retinal ganglion cell degeneration and other optic neuropathies.

Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic nerve crush byin vivoimaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for ∼11% of the total SMI-32–positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic nerve crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32–positive RGCs.

Purpose Elastic light backscattering spectroscopy (ELBS) has exquisite sensitivity to the ultrastructural properties of tissue and thus has been applied to detect various diseases associated with ultrastructural alterations in their early stages. This study aims to test whether ELBS can detect early damage in retinal ganglion cells (RGCs). Methods We used a mouse model of partial optic nerve crush (pONC) to induce rapid RGC death. We confirmed RGC loss by axon counting and characterized the changes in retinal morphology by optical coherence tomography (OCT) and in retinal function by full-field electroretinogram (ERG), respectively. To quantify the ultrastructural properties, elastic backscattering spectroscopic analysis was implemented in the wavelength-dependent images recorded by reflectance confocal microscopy. Results At 3 days post-pONC injury, no significant change was found in the thickness of the RGC layer or in the mean amplitude of the oscillatory potentials measured by OCT and ERG, respectively; however, we did observe a significantly decreased number of axons compared with the controls. At 3 days post-pONC, we used ELBS to calculate the ultrastructural marker (D), the shape factor quantifying the shape of the local mass density correlation functions. It was significantly reduced in the crushed eyes compared with the controls, indicating the ultrastructural fragmentation in the crushed eyes. Conclusions Elastic light backscattering spectroscopy detected ultrastructural neuronal damage in RGCs following the pONC injury when OCT and ERG tests appeared normal. Our study suggests a potential clinical method for detecting early neuronal damage prior to anatomical alterations in the nerve fiber and ganglion cell layers.

In this short review, Puyang and her colleagues compared the results from three laboratories on the dendritic and functional degeneration of retinal ganglion cells (RGCs) in mouse models of experimental glaucoma [1–4]. Acute or chronic ocular hypertension was induced in mice, and different techniques were applied to identify RGC types. The dendritic alternations of RGCs were examined following the induction of ocular hypertension, and their light response properties were characterized by the multi-electrode array (MEA) recording. These studies support the notion that the morphological and functional degeneration of RGCs are subtype-dependent in experimental glaucoma.

PURPOSE. We investigated the progressive degeneration of retinal and superior collicular functions in a mouse model of sustained ocular hypertension. METHODS. Focal laser illumination and injection of polystyrene microbeads were used to induce chronic ocular hypertension. Retinal ganglion cell (RGC) loss was characterized by in vivo optical coherence tomography (OCT) and immunohistochemistry. Retinal dysfunction was also monitored by the full-field ERG. Retinal ganglion cell light responses were recorded using a 256-channel multielectrode array (MEA), and RGC subtypes were characterized by noncentered spike-triggered covariance (STC-NC) analysis. Single-unit extracellular recordings from superficial layers of the superior colliculus (SC) were performed to examine the receptive field (RF) properties of SC neurons. RESULTS. The elevation of intraocular pressure (IOP) lasted 4 months in mice treated with a combination of laser photocoagulation and microbead injection. Progressive RGC loss and functional degeneration were confirmed in ocular hypertensive (OHT) mice. These mice had fewer visually responsive RGCs than controls. Using the STC-NC analysis, we classified RGCs into ON, OFF, and ON-OFF functional subtypes. We showed that ON and OFF RGCs were more susceptible to the IOP elevation than ON-OFF RGCs. Furthermore, SC neurons of OHT mice had weakened responses to visual stimulation and exhibited mismatched ON and OFF subfields and irregular RF structure. CONCLUSIONS. We demonstrated that the functional degeneration of RGCs is subtypedependent and that the ON and OFF pathways from the retina to the SC were disrupted. Our study provides a foundation to investigate the mechanisms underlying the progressive vision loss in experimental glaucoma.