Transformation of motion pattern selectivity from retina to superior colliculus.

The superior colliculus (SC) is a prominent and conserved visual center in all vertebrates. In mice, the most superficial lamina of the SC is enriched with neurons that are selective for the moving direction of visual stimuli. Here we study how these direction selective neurons respond to complex motion patterns known as plaids, using two-photon calcium imaging in awake male and female mice. The plaid pattern consists of two superimposed sinusoidal gratings moving in different directions, giving an apparent pattern direction that lies between the directions of the two component gratings. Most direction selective neurons in the mouse SC respond robustly to the plaids and show a high selectivity for the moving direction of the plaid pattern but not of its components. Pattern motion selectivity is seen in both excitatory and inhibitory SC neurons and is especially prevalent in response to plaids with large cross angles between the two component gratings. However, retinal inputs to the SC are ambiguous in their selectivity to pattern versus component motion. Modeling suggests that pattern motion selectivity in the SC can arise from a nonlinear transformation of converging retinal inputs. In contrast, the prevalence of pattern motion selective neurons is not seen in the primary visual cortex (V1). These results demonstrate an interesting difference between the SC and V1 in motion processing and reveal the SC as an important site for encoding pattern motion.Significance Statement An important function of the visual system is to encode the direction of complex motion patterns in the environment. Studies using the plaid stimulus have revealed neurons in different cortical areas that are tuned to either pattern motion or component motion, but how neurons in the SC respond to plaids has not been studied. Here we show that direction selective neurons in the mouse SC respond to plaids with a clear pattern motion selectivity, at a level not seen in the retina or V1. Our results thus provide new information regarding the function and organization of the early visual system and highlight the importance of SC circuits in computing complex motion.

Mapping visual functions onto molecular cell types in the mouse superior colliculus.

The superficial superior colliculus (sSC) carries out diverse roles in visual processing and behaviors, but how these functions are delegated among collicular neurons remains unclear. Here, using single-cell transcriptomics, we identified 28 neuron subtypes and subtype-enriched marker genes from tens of thousands of adult mouse sSC neurons. We then asked whether the sSC's molecular subtypes are tuned to different visual stimuli. Specifically, we imaged calcium dynamics in single sSC neurons in vivo during visual stimulation and then mapped marker gene transcripts onto the same neurons ex vivo. Our results identify a molecular subtype of inhibitory neuron accounting for ∼50% of the sSC's direction-selective cells, suggesting a genetic logic for the functional organization of the sSC. In addition, our studies provide a comprehensive molecular atlas of sSC neuron subtypes and a multimodal mapping method that will facilitate investigation of their respective functions, connectivity, and development.

Phase advancing is a common property of multiple neuron classes in the mouse retina.

Behavioral interactions with moving objects are challenged by response latencies within the sensory and motor nervous systems. In vision, the combined latency from phototransduction and synaptic transmission from the retina to central visual areas amounts to 50-100 ms, depending on stimulus conditions. Time required for generating appropriate motor output adds to this latency and further compounds the behavioral delay. Neuronal adaptations that help counter sensory latency within the retina have been demonstrated in some species, but how general these specializations are, and where in the circuitry they originate, remains unclear. To address this, we studied the timing of object motion-evoked responses at multiple signaling stages within the mouse retina using two-photon fluorescence calcium and glutamate imaging, targeted whole-cell electrophysiology, and computational modeling. We found that both ON and OFF-type ganglion cells, as well as the bipolar cells that innervate them, temporally advance the position encoding of a moving object and so help counter the inherent signaling delay in the retina. Model simulations show that this predictive capability is a direct consequence of the spatial extent of the cells' linear visual receptive field, with no apparent specialized circuits that help predict beyond it.Significance StatementSignal transduction and synaptic transmission within sensory signaling pathways costs time. Not a lot of time, just tens to a few hundred milliseconds depending on the sensory system, but enough to challenge fast behavioral interactions under dynamic stimulus conditions, like catching a moving fly. To counter neuronal delays, nervous systems of many species use anticipatory mechanisms. One such mechanism in the mammalian visual system helps predict the future position of a moving target through a process called phase advancing. Here we ask for functionally diverse neuron populations in the mouse retina how common is phase advancing and demonstrate that it is common and generated at multiple signaling stages.

Lack of Evidence for Stereotypical Direction Columns in the Mouse Superior Colliculus.

Neurons in the visual system can be spatially organized according to their response properties such as receptive field location and feature selectivity. For example, the visual cortex of many mammalian species contains orientation and direction columns where neurons with similar preferences are clustered. Here, we examine whether such a columnar structure exists in the mouse superior colliculus (SC), a prominent visual center for motion processing. By performing large-scale physiological recording and two-photon calcium imaging in adult male and female mice, we show that direction-selective neurons in the mouse SC are not organized into stereotypical columns as a function of their preferred directions, although clusters of similarly tuned neurons are seen in a minority of mice. Nearby neurons can prefer similar or opposite directions in a largely position-independent manner. This finding holds true regardless of animal state (anesthetized vs awake, running vs stationary), SC depth (most superficial lamina vs deeper in the SC), research technique (calcium imaging vs electrophysiology), and stimulus type (drifting gratings vs moving dots, full field vs small patch). Together, these results challenge recent reports of region-specific organizations in the mouse SC and reveal how motion direction is represented in this important visual center.

Author Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

The version of this paper originally published cited a preprint version of ref. 12 instead of the published version (Proc. Natl. Acad. Sci. USA 115, 5594-5599; 2018), which was available before this Nature Methods paper went to press. The reference information has been updated in the PDF and HTML versions of the article.

Publisher Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

In the version of this paper originally published, important figure labels in Fig. 3d were not visible. An image layer present in the authors' original figure that included two small dashed outlines and text labels indicating ROI 1 and ROI 2, as well as a scale bar and the name of the cell label, was erroneously altered during image processing. The figure has been corrected in the HTML and PDF versions of the paper.

Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) that are functionally brighter; detect submicromolar to millimolar amounts of glutamate; and have blue, cyan, green, or yellow emission profiles. These variants could be imaged in vivo in cases where original iGluSnFR was too dim, resolved glutamate transients in dendritic spines and axonal boutons, and allowed imaging at kilohertz rates.