Neurons in sensory systems often pool inputs over arrays of presynaptic cells, giving rise to functional subunits inside a neuron’s receptive field. The organization of these subunits provides a signature of the neuron’s presynaptic functional connectivity and determines how the neuron integrates sensory stimuli. Here we introduce the method of spike-triggered non-negative matrix factorization for detecting the layout of subunits within a neuron’s receptive field. The method only requires the neuron’s spiking responses under finely structured sensory stimulation and is therefore applicable to large populations of simultaneously recorded neurons. Applied to recordings from ganglion cells in the salamander retina, the method retrieves the receptive fields of presynaptic bipolar cells, as verified by simultaneous bipolar and ganglion cell recordings. The identified subunit layouts allow improved predictions of ganglion cell responses to natural stimuli and reveal shared bipolar cell input into distinct types of ganglion cells.

We study the effects of a probabilistic refractory period in the collective behavior of coupled discrete-time excitable cells (SIRS-like cellular automata). Using mean-field analysis and simulations, we show that a synchronized phase with stable collective oscillations exists even with non-deterministic refractory periods. Moreover, further increasing the coupling strength leads to a reentrant transition, where the synchronized phase loses stability. In an intermediate regime, we also observe bistability (and consequently hysteresis) between a synchronized phase and an active but incoherent phase without oscillations. The onset of the oscillations appears in the mean-field equations as a Neimark-Sacker bifurcation, the nature of which (i.e. super-or subcritical) is determined by the first Lyapunov coefficient. This allows us to determine the borders of the oscillating and of the bistable regions. The mean-field prediction thus obtained agrees quantitatively with simulations of complete graphs and, for random graphs, qualitatively predicts the overall structure of the phase diagram. The latter can be obtained from simulations by defining an order parameter q suited for detecting collective oscillations of excitable elements. We briefly review other commonly used order parameters and show (via data collapse) that q satisfies the expected finite size scaling relations.

Salamanders have been habitual residents of research laboratories for more than a century, and their history in science is tightly interwoven with vision research. Nevertheless, many vision scientists – even those working with salamanders – may be unaware of how much our knowledge about vision, and particularly the retina, has been shaped by studying salamanders. In this review, we take a tour through the salamander history in vision science, highlighting the main contributions of salamanders to our understanding of the vertebrate retina. We further point out specificities of the salamander visual system and discuss the perspectives of this animal system for future vision research.

Graphical abstract

12Waves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) 13 layer, driven by directly interconnected cholinergic starburst amacrine cells (the only known 14 retinal cholinergic cells) from postnatal day (P) 0-10, followed by waves driven by 15 glutamatergic bipolar cells. We found transient clusters of cholinergic RGC-like cells around 16 the optic disc during the period of cholinergic waves. They migrate towards the periphery 17 between P2-9 and then they disappear. Pan-retinal multielectrode array recordings reveal that 18 cholinergic wave origins follow a similar developmental center-to-periphery pattern. Electrical 19 imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. 20 We propose that these activity hotspots are sites for wave initiation and are related to the 21 cholinergic cell clusters, reminiscent of activity in transient subplate neurons in the developing 22 cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks 23 during the critical period for brain wiring. 24 25 26During development, neural wiring is refined through activity-dependent processes 27 (Blankenship and Feller, 2010;Luhmann et al, 2016). Spontaneous activity emerges long 28 before sensory experience is possible, displaying unique expression patterns in different CNS 29 areas. In the visual system, this activity is manifested by waves of spikes spreading across the 30 retinal ganglion cell (RGC) layer (Meister et al, 1991). Several studies have demonstrated that 31 retinal waves guide the development of visual connectivity (Huberman et al, 2008; Assali et 32 al, 2014). 33 The cellular mechanisms underlying wave generation change with development, indicated 34 by profound changes in the wave spatiotemporal features (Maccione et al, 2014). In mouse, the 35 drive for wave generation/propagation switches from gap junction communication (Stage-1, 36 prenatal) to cholinergic neurotransmission originating in starburst amacrine cells (SACs) 37 (Stage-2, late gestation to P9) (Feller et al, 1996). Control then switches to glutamatergic 38 bipolar cells before waves disappear around eye opening (Stage-3, P10-13). During Stage-2, 39 SACs make direct homotypic connections, leading to lateral activity propagation across their 40 network (Zheng et al, 2004). Experimental (Zheng et al, 2006; Ford et al, 2012) and theoretical 41 studies (Butts et al, 1999; Hennig et al, 2009; Matzakos-Karvouniari et al, 2019) suggest that 42 SACs play a fundamental role in defining wave dynamics by driving both wave initiation and 43 propagation. Active SACs impose a refractory period, creating boundaries for activity 44 propagation and controlling wave frequency. However, wave properties are not static during 45 the prolonged Stage-2 period, exhibiting a gradual increase in wave frequency and size, 46 followed by substantial shrinkage from P7 (Maccione et al, 2014). This suggests that Stage-2 47 57 expands, reaching the retinal periphery around P6-7....

Saccades are a fundamental part of natural vision. They interrupt fixations of the visual gaze and rapidly shift the image that falls onto the retina. These stimulus dynamics can cause activation or suppression of different retinal ganglion cells, but how they affect the encoding of visual information in different types of ganglion cells is largely unknown. Here, we recorded spiking responses to saccade-like shifts of luminance gratings from ganglion cells in isolated marmoset retinas and investigated how the activity depended on the combination of pre- and post-saccadic images. All identified cell types, On and Off parasol and midget cells as well as a type of Large Off cells, displayed distinct response patterns, including particular sensitivity to either the pre- or the post-saccadic image or combinations thereof. In addition, Off parasol and Large Off cells, but not On cells, showed pronounced sensitivity to whether the image changed across the transition. Stimulus sensitivity of On cells could be explained based on their responses to step changes in light intensity, whereas Off cells, in particular, parasol and the Large Off cells, seem to be affected by additional interactions that are not triggered during simple light-intensity flashes. Together, our data show that ganglion cells in the primate retina are sensitive to different combinations of pre- and post-saccadic visual stimuli. This contributes to the functional diversity of the retina’s output signals and to asymmetries between On and Off pathways and provides evidence of signal processing beyond what is triggered by isolated steps in light intensity.Significance Statement:Sudden eye movements (saccades) shift our direction of gaze, bringing new images in focus on our retinas. To study how retinal neurons deal with these rapid image transitions, we recorded spiking activity from ganglion cells, the retina's output neurons, in isolated retinas of marmoset monkeys while shifting a projected image in a saccade-like fashion across the retina. We found that the cells do not just respond to the newly fixated image, but that different types of ganglion cells display different sensitivities to the pre- and post-saccadic stimulus patterns. Certain Off cells, for example, are sensitive to changes in the image across transitions, which contributes to differences between On and Off information channels and extends the range of encoded stimulus features.

Saccades are a fundamental part of natural vision. They interrupt fixations of the visual gaze and rapidly shift the image that falls onto the retina. These stimulus dynamics can cause activation or suppression of different retinal ganglion cells, but how they affect the encoding of visual information in different types of ganglion cells is largely unknown. Here, we recorded spiking responses to saccade-like shifts of luminance gratings from ganglion cells in isolated marmoset retinas and investigated how the activity depended on the combination of pre- and post-saccadic images. All identified cell types, On and Off parasol and midget cells as well as a type of Large Off cells, displayed distinct response patterns, including particular sensitivity to either the pre- or the post-saccadic image or combinations thereof. In addition, Off parasol and Large Off cells, but not On cells, showed pronounced sensitivity to whether the image changed across the transition. Stimulus sensitivity of On cells could be explained based on their responses to step changes in light intensity, whereas Off cells, in particular, parasol and the Large Off cells, seem to be affected by additional interactions that are not triggered during simple light-intensity flashes. Together, our data show that ganglion cells in the primate retina are sensitive to different combinations of pre- and post-saccadic visual stimuli. This contributes to the functional diversity of the retina's output signals and to asymmetries between On and Off pathways and provides evidence of signal processing beyond what is triggered by isolated steps in light intensity.

Developing neurons become spontaneously active while growing blood vessels begin to irrigate their surroundings. However, surprising little is known about early interactions between neural activity and angiogenesis. In the neonatal mouse retina, spontaneous waves of impulses sweep across the ganglion cell layer (GCL), just underneath the growing superficial vascular plexus. We discovered clusters of transient auto-fluorescent cells in the GCL, forming an annulus that co-localizes with the frontline of the growing plexus. Blood vessel density is highest within cluster areas, suggesting their involvement in angiogenesis. Once the clusters and blood vessels reach the retinal periphery by the end of the first postnatal week, the clusters disappear, eliminated by microglial phagocytosis. Electrical imaging suggests that they have their own electrophysiological signature. Blocking Pannexin1 (PANX1) hemi-channels with probenecid blocks the waves and the fluorescent clusters disappear following prolonged exposure to the drug. Spontaneous waves initiation points follow a developmental center-to-periphery progression similar to the cluster cells. We suggest that these transient cells are specialized, hyperactive neurons residing in the GCL. They generate spontaneous activity hotspots, thereby triggering waves through purinergic paracrine signaling via PANX1 hemi-channels. The strong activity generated around these hotspots triggers angiogenesis, attracting new blood vessels that provide local oxygen supply. Signaling through PANX-1 attracts microglia that establish contact with these cells, eventually leading to their elimination by phagocytosis. These cluster cells may provide the first evidence that specialized transient neuronal populations guide angiogenesis in the developing CNS through neural activity.