Efficient mapping of the thalamocortical monosynaptic connectivity in vivo by tangential insertions of high-density electrodes in the cortex.

The thalamus provides the principal input to the cortex and therefore understanding the mechanisms underlying cortical integration of sensory inputs requires to characterize the thalamocortical connectivity in behaving animals. Here, we propose tangential insertions of high-density electrodes into mouse cortical layer 4 as a method to capture the activity of thalamocortical axons simultaneously with their synaptically connected cortical neurons. This technique can reliably monitor multiple parallel thalamic synaptic inputs to cortical neurons, providing an efficient approach to map thalamocortical connectivity in both awake and anesthetized mice.

Retinal input integration in excitatory and inhibitory neurons in the mouse superior colliculus in vivo.

The superior colliculus (SC) is a midbrain structure that receives inputs from retinal ganglion cells (RGCs). The SC contains one of the highest densities of inhibitory neurons in the brain but whether excitatory and inhibitory SC neurons differentially integrate retinal activity in vivo is still largely unknown. We recently established a recording approach to measure the activity of RGCs simultaneously with their postsynaptic SC targets in vivo, to study how SC neurons integrate RGC activity. Here, we employ this method to investigate the functional properties that govern retinocollicular signaling in a cell type-specific manner by identifying GABAergic SC neurons using optotagging in VGAT-ChR2 mice. Our results demonstrate that both excitatory and inhibitory SC neurons receive comparably strong RGC inputs and similar wiring rules apply for RGCs innervation of both SC cell types, unlike the cell type-specific connectivity in the thalamocortical system. Moreover, retinal activity contributed more to the spiking activity of postsynaptic excitatory compared to inhibitory SC neurons. This study deepens our understanding of cell type-specific retinocollicular functional connectivity and emphasizes that the two major brain areas for visual processing, the visual cortex and the SC, differently integrate sensory afferent inputs.

Retinal waves align the concentric orientation map in mouse superior colliculus to the center of vision.

Neurons in the mouse superior colliculus (SC) are arranged in a concentric orientation map, which is aligned to the center of vision and the optic flow experienced by the mouse. The origin of this map remains unclear. Here, we propose that spontaneous retinal waves during development provide a scaffold to establish the concentric orientation map within the SC and its alignment to the optic flow. We test this hypothesis by modeling the orientation-tuned SC neurons that receive ON/OFF retinal inputs. Our model suggests that the propagation direction bias of stage III retinal waves, together with OFF-delayed responses, shapes the spatial organization of the orientation map. The OFF delay establishes orientation-tuned neurons by segregating their ON/OFF receptive subfields, the wave-like activities form the concentric pattern, and the direction biases align the map to the center of vision. Together, retinal waves may play an instructive role in establishing functional properties of single SC neurons and their spatial organization within maps.

High-density electrode recordings reveal strong and specific connections between retinal ganglion cells and midbrain neurons.

The superior colliculus is a midbrain structure that plays important roles in visually guided behaviors in mammals. Neurons in the superior colliculus receive inputs from retinal ganglion cells but how these inputs are integrated in vivo is unknown. Here, we discovered that high-density electrodes simultaneously capture the activity of retinal axons and their postsynaptic target neurons in the superior colliculus, in vivo. We show that retinal ganglion cell axons in the mouse provide a single cell precise representation of the retina as input to superior colliculus. This isomorphic mapping builds the scaffold for precise retinotopic wiring and functionally specific connection strength. Our methods are broadly applicable, which we demonstrate by recording retinal inputs in the optic tectum in zebra finches. We find common wiring rules in mice and zebra finches that provide a precise representation of the visual world encoded in retinal ganglion cells connections to neurons in retinorecipient areas.

Tangential high-density electrode insertions allow to simultaneously measure neuronal activity across an extended region of the visual field in mouse superior colliculus.

BACKGROUND: The superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, which render the measure of neuronal activity from a large population of neurons in the SC technically difficult to perform. NEW METHOD: To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo. This method permits a large number of recording sites (~200) inside the SC circuitry allowing to record from a large population of SC neurons along a vast area of retinotopic space. RESULTS: This approach provides a unique opportunity to measure the activity of SC neuronal populations over up to ~2 mm of SC tissue reporting for the first time the continuous receptive fields coverage of almost the entire SC retinotopy. Here we describe how to perform targeted tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo in the upper visual layers. Furthermore, we describe how to combine this approach with optogenetic tools for cell-type identification on the population level. COMPARISON WITH EXISTING METHODS: Vertical insertion has been a standard way to record visual responses in the SC. Inserting multi-shank probes vertically allows to cover a larger region of the SC but misses both the complete extent of the available retinotopy and the continuous measure allowed by the high density of recording sites on Neuropixels probes. CONCLUSION: Altogether tangential insertions in the upper visual layers of the mouse SC using Neuropixels permit for the first time to access a majority of the retinotopically organized visual representation of the world at an unprecedented precision.