What we think we do

Luminance encoding in the human brain

The main pathway through which visual signals are routed to cortex includes the dorsal lateral geniculate nucleus and primary visual cortex. However, recent work has identified in the mouse a new separate pathway. This pathway includes the dorso-thalamic perihabenula and the ventromedial prefrontal cortex which plays a key role in mood regulation. In addition to studying this newly identified pathway in the mouse, our lab uses functional MRI to test whether the new pathway exists also in humans, and if so, whether it contributes to mood regulation.

Dr. Shai Sabbah Lab | Brain research | Dr.-Shai-Sabbah-Main-figure_Background-of-top-banner-Orientation-selectivity-in-the-retina-and-cortex_-FeatureIMG

Retinal orientation selectivity

Orientation selective neurons, which respond to edges presented at certain orientations, have been documented in the retina and cortex. However, it is unknown whether cortical orientation selectivity is created de novo in the cortex, or instead derived from processing and integration of orientation-selective signals arriving from the retina, presumably through thalamic and collicular relay neurons. To understand the basis of retinal orientation selectivity and its contribution to cortical orientation selectivity, we study the topographic variation, morphology, physiology, and central projections of orientation-selective retinal ganglion cells.

Polar plot showing response amplitude (normalized to maximum) for eight different directions (N, nasal; D, dorsal; T, temporal; V, ventral). This orientation-selective cell responds best to gratings drifting along the ventral-dorsal axis, corresponding to preference for stimuli that are orientated along the nasal-temporal axis.

Two-photon guided patch-clamp recording

Calcium transients of neurons in an isolated retina in response to sinusoidal contrast gratings drifting in eight directions at 45° intervals.

| Shai Sabbah Laboratory | Bra Featur IMGin research | Main-figure_translatory-axes

Direction selectivity in the retina and brain

Visual motion tells us how objects are moving in the world, and how we are moving within that world. Our work has recently transformed the understanding of this system’s architecture in the context of the whole animal. We studied how the global geometry of retinal direction selectivity relates to optic flow induced by self-motion. By intensive global mapping using two-photon calcium imaging, electrophysiology, and retrograde tracing, we revealed a surprising spherical geometry of retinal direction selectivity. We identified four subtypes of direction-selective ganglion cells, each of which aligned its directional preferences with optic flow produced by the mouse’s movement along either the body or gravitational axis. This has fascinating implications for all the perceptual and visuomotor functions supported by these cells, including image stabilization, cortical motion perception, and gaze shifts to moving targets. Now a days, we study how signals from the various subtypes of direction-selective ganglion cells interact in the brain to generate an estimate of the direction of motion and trigger compensatory eye movements. We also study the mechanistic basis of retinal direction selectivity, and specifically, the asymmetry of input to direction-selective retinal ganglion cells from presynaptic cells.

Rotatory and translatory visual vector fields

Dr. Shai Sabbah Laboratory | Brain research | Brain-circuits

Brain circuits that mediate the effects of light on mood

Light has a critical impact on mood disorders in ways we are only beginning to recognize, with the potential for the development of effective, relatively non-invasive therapies. However, until now, surprisingly little has been reported on the mechanisms underlying the effects of light on mood. We characterize a newly discovered pathway that links specialized retinal photoreceptors, the dorsal thalamus, and the prefrontal cortex. This pathway apparently mediates the diverse effects of diffuse light intensity on mood. We dissect the synaptic input properties, behavioral output, and mechanistic basis of this new pathway, with special emphasis on its contribution to the pathophysiology of depression. To this end, we combine complementary behavioral, electrophysiological, functional imaging, and genetic manipulation approaches. This study, we hope, will pave the way toward a new understanding of the effect of light on mood, which can have implications both for research and in the clinic.

A newly-discovered pathway that bypasses the suprachiasmatic nucleus and regulates mood

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate a newly-identified thalamic nucleus, the perihabenular nucleus (PHb), which in turn innervates the ventromedial prefrontal cortex (vmPFC) that has a key role in mood regulation (blue line). This retino-thalamo-frontocortical pathway bypasses another pathway that appears to transmit ipRGC signals, and includes the master circadian oscillator (suprachiasmatic nucleus, SCN) and paraventricular thalamic nucleus (PVT). Accordingly, the new pathway has been shown to mediate a direct effect of light on mood without any circadian effects.

Shai-Sabaah Laboratory | Brain research | amacrine-cells

Luminance-dependent modulation of retinal function

The mammalian retina maintains high sensitivity over an extraordinary range of luminance levels, ranging from starlight to bright sunlight. This is achieved by switching between the rod and cone systems, and within each system, by employing light adaptation mechanisms that preserve a contrast-invariant response. While dopamine is known to modulate retinal network activity in proportion to luminance, the luminance-dependent signals and the circuits that transmit them to elicit light adaptation, remain elusive. Our work identified a family of luxotonic amacrine cells in which activity increases with luminance level and are poised to modulate retinal function in a luminance-dependent manner. We determine the kinetics of the synaptic input to luxotonic amacrine cells, identify their pre- and postsynaptic partners, and test their role in retinal light adaptation. Implementing optogenetics, chemogenetics, functional imaging, whole-cell electrophysiology, and serial section electron microscopy, this study will help further our understanding of a fundamental adaptative mechanism in a key sensory modality.

RAC1 receives luminance signals from M2 ipRGCs (green) via electrical transmission through gap junctions, but not from M1 ipRGCs (red). Consequently, the long axons of RAC1 may distribute these luminance signals across long distances and modulate retinal function in a luminance-dependent manner.

Identification of ribbon synapses between a bipolar cell (BC) axon and a dendrite of a retinal ganglion cell (RGC).