Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system.

Special nuclear layer contacts between starburst amacrine cells in the mouse retina.

Starburst amacrine cells are a prominent neuron type in the mammalian retina that has been well-studied for its role in direction-selective information processing. One specific property of these cells is that their dendrites tightly stratify at specific depths within the inner plexiform layer (IPL), which, together with their unique expression of choline acetyltransferase (ChAT), has made them the most common depth marker for studying other retinal neurons in the IPL. This stratifying property makes it unexpected that they could routinely have dendrites reaching into the nuclear layer or that they could have somatic contact specializations, which is exactly what we have found in this study. Specifically, an electron microscopic image volume of sufficient size from a mouse retina provided us with the opportunity to anatomically observe both microscopic details and collective patterns, and our detailed cell reconstructions revealed interesting cell-cell contacts between starburst amacrine neurons. The contact characteristics differ between the respective On and Off starburst amacrine subpopulations, but both occur within the soma layers, as opposed to their regular contact laminae within the inner plexiform layer.

Cyclic structure with cellular precision in a vertebrate sensorimotor neural circuit.

Neuronal wiring diagrams reconstructed by electron microscopy1,2,3,4,5 pose new questions about the organization of nervous systems following the time-honored tradition of cross-species comparisons.6,7 The C. elegans connectome has been conceptualized as a sensorimotor circuit that is approximately feedforward,8,9,10,11 starting from sensory neurons proceeding to interneurons and ending with motor neurons. Overrepresentation of a 3-cell motif often known as the "feedforward loop" has provided further evidence for feedforwardness.10,12 Here, we contrast with another sensorimotor wiring diagram that was recently reconstructed from a larval zebrafish brainstem.13 We show that the 3-cycle, another 3-cell motif, is highly overrepresented in the oculomotor module of this wiring diagram. This is a first for any neuronal wiring diagram reconstructed by electron microscopy, whether invertebrate12,14 or mammalian.15,16,17 The 3-cycle of cells is "aligned" with a 3-cycle of neuronal groups in a stochastic block model (SBM)18 of the oculomotor module. However, the cellular cycles exhibit more specificity than can be explained by the group cycles-recurrence to the same neuron is surprisingly common. Cyclic structure could be relevant for theories of oculomotor function that depend on recurrent connectivity. The cyclic structure coexists with the classic vestibulo-ocular reflex arc for horizontal eye movements,19 and could be relevant for recurrent network models of temporal integration by the oculomotor system.20,21.