The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells.DOI: http://dx.doi.org/10.7554/eLife.06262.001

Highlights d Repetitive visual stimulation eliminates center and boosts surround response in SAC d Changes in center-surround abolish SAC direction selectivity and shift its response d Shifted SAC responses alter inhibition timing and reverse DSGC directional tuning d SAC center and surround elicit directional responses in DSGC to opposite directions

Here we present a protocol for preparation of acute brain slices. This procedure is a critical element for electrophysiological patch-clamp experiments that largely determines the quality of results. It has been shown that omitting the cooling step during cutting procedure is beneficial in obtaining healthy slices and cells, especially when dealing with highly myelinated brain structures from mature animals. Even though the precise mechanism whereby elevated temperature supports neural health can only be speculated upon, it stands to reason that, whenever possible, the temperature in which the slicing is performed should be close to physiological conditions to prevent temperature related artifacts. Another important advantage of this method is the simplicity of the procedure and therefore the short preparation time. In the demonstrated method adult mice are used but the same procedure can be applied with younger mice as well as rats. Also, the following patch clamp experiment is performed on horizontal cerebellar slices, but the same procedure can also be used in other planes as well as other posterior areas of the brain. Video LinkThe video component of this article can be found at

SummaryA key feature in sensory processing is center-surround receptive field antagonism. Retinal direction-selectivity (DS) relies on asymmetric inhibition from starburst amacrine cells (SAC) to direction selective ganglion cells (DSGC). SAC exhibit antagonistic center-surround, depolarizing to light increments and decrements in their center and surround, respectively, but the role of this property in DS remains elusive. We found that a repetitive stimulation exhausts SAC center and enhances its surround and used it to distinguish center-from surround-mediated responses. Center, but not surround stimulation, induced direction-selective responses in SAC, as predicted by an elementary spatiotemporal model. Nevertheless, both SAC center and surround elicited direction-selective responses in DSGCs, but to opposite directions. Physiological and morphology-based modeling data show that the opposed responses resulted from inverted DSGC’s excitatory-inhibitory temporal balance, indicating that SAC response time rules DS. Our findings reveal antagonistic center-surround mechanisms for DS, and demonstrate how context-dependent center-surround reorganization enables flexible computations.

SummaryThe mammalian retina is considered an autonomous circuit, yet work dating back to Ramon y Cajal indicates that it receives inputs from the brain. How such inputs affect retinal processing has remained unknown. We identified brain-to-retina projections of histaminergic neurons from the mouse hypothalamus, which densely innervated the dorsal retina. Histamine application, or chemogenetic activation of histaminergic axons, altered spontaneous and light-evoked activity of various retinal ganglion cells (RGCs), including direction-selective RGCs. These cells exhibited broader directional tuning and gained responses to high motion velocities. Such changes could improve vision when objects move fast across the visual field (e.g. while running), which fits with the known increased activity of histaminergic neurons during arousal. In humans, an antihistamine drug non-uniformly modulated visual sensitivity across the visual field, indicating an evolutionary conserved function of the histaminergic system. Our findings expose a previously unappreciated role for brain-to-retina projections in modulating retinal function.