Synchronous inhibitory pathways create both efficiency and diversity in the retina.

Sensory receptive fields combine features that originate in different neural pathways. Retinal ganglion cell receptive fields compute intensity changes across space and time using a peripheral region known as the surround, a property that improves information transmission about natural scenes. The visual features that construct this fundamental property have not been quantitatively assigned to specific interneurons. Here, we describe a generalizable approach using simultaneous intracellular and multielectrode recording to directly measure and manipulate the sensory feature conveyed by a neural pathway to a downstream neuron. By directly controlling the gain of individual interneurons in the circuit, we show that rather than transmitting different temporal features, inhibitory horizontal cells and linear amacrine cells synchronously create the linear surround at different spatial scales and that these two components fully account for the surround. By analyzing a large population of ganglion cells, we observe substantial diversity in the relative contribution of amacrine and horizontal cell visual features while still allowing individual cells to increase information transmission under the statistics of natural scenes. Established theories of efficient coding have shown that optimal information transmission under natural scenes allows a diverse set of receptive fields. Our results give a mechanism for this theory, showing how distinct neural pathways synthesize a sensory computation and how this architecture both generates computational diversity and achieves the objective of high information transmission.

Comparative characterization of single cell activity in the globus pallidus internus of patients with dystonia or Tourette syndrome.

Altered processing in the basal ganglia has been described both in dystonia and Tourette's syndrome (TS). Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become a recognized treatment for dystonia and has been used successfully to alleviate tics in TS. This study evaluates possible differences of GPi linear and nonlinear neuronal discharge characteristics between patients with dystonia and TS. Nine patients with primary dystonia and six patients with TS were studied during functional stereotactic neurosurgical operations for implantation of DBS electrodes under general anesthesia. Six patients with primary dystonia under local anesthesia served as non-anesthetized controls. Single-unit activity recordings in the GPi were obtained during routine microelectrode recording and mapping to delineate nuclear borders and to identify the sensorimotor subregions. Anesthesia profoundly decreased neuronal activity in patients with dystonia. Dystonia patients showed marginally higher mean firing rates in the GPi compared to TS patients (P = 0.06). Although the average total number of bursts and the mean peak frequency in bursts did not differ between groups, the mean spikes in bursts were higher in dystonia patients (P < 0.05). Nonlinear time series analysis metrics, measured as complexity of Lempel-Ziv and maximum approximate entropy, revealed higher randomness in TS compared to dystonia patients (P < 0.05). The percentage of oscillating neurons in spike trains was higher in dystonia compared to TS (P < 0.05). Our data provide evidence for differences of the neuronal dynamic complexity, randomness and oscillatory modulation of spike trains in the GPi between dystonia and TS. Such differences, although subtle, might contribute to the specific clinical phenomenology secondary to disordered neuronal basal ganglia processing.

Disinhibitory gating of retinal output by transmission from an amacrine cell.

Inhibitory interneurons help transform the input of a neural circuit into its output. Such interneurons are diverse, and most have unknown function. To study the function of single amacrine cells in the intact salamander retina, we recorded extracellularly from a population of ganglion cells with a multielectrode array, while simultaneously recording from or injecting current into single Off-type amacrine cells that had linear responses. We measured how visual responses of the amacrine cell interacted both with other visual input to the ganglion cell and with transmission between the two cells. We found that on average, visual responses from Off-type amacrine cells inhibited nearby Off-type ganglion cells. By recording and playing back the light-driven membrane potential fluctuations of amacrine cells during white noise visual stimuli, we found that paradoxically, increasing the light-driven modulations of inhibitory amacrine cells increased the firing rate of nearby Off-type ganglion cells. By measuring the correlations and transmission between amacrine and ganglion cells, we found that, on average, the amacrine cell hyperpolarizes before the ganglion cell fires, generating timed disinhibition just before the ganglion cell spikes. In addition, we found that amacrine to ganglion cell transmission is nonlinear in that increases in ganglion cell activity produced by amacrine hyperpolarization were greater than decreases in activity produced by amacrine depolarization. We conclude that the primary mode of action of this class of amacrine cell is to actively gate the ganglion cell response by a timed release from inhibition.

Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells.

Our understanding of how mammalian sensory circuits are organized and develop has long been hindered by the lack of genetic markers of neurons with discrete functions. Here, we report a transgenic mouse selectively expressing GFP in a complete mosaic of transient OFF-alpha retinal ganglion cells (tOFF-alphaRGCs). This enabled us to relate the mosaic spacing, dendritic anatomy, and electrophysiology of these RGCs to their complete map of projections in the brain. We find that tOFF-alphaRGCs project exclusively to the superior colliculus (SC) and dorsal lateral geniculate nucleus and are restricted to a specific laminar depth within each of these targets. The axons of tOFF-alphaRGC are also organized into columns in the SC. Both laminar and columnar specificity develop through axon refinement. Disruption of cholinergic retinal waves prevents the emergence of columnar- but not laminar-specific tOFF-alphaRGC connections. Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype.

A retinal circuit that computes object motion.

Certain ganglion cells in the retina respond sensitively to differential motion between the receptive field center and surround, as produced by an object moving over the background, but are strongly suppressed by global image motion, as produced by the observer's head or eye movements. We investigated the circuit basis for this object motion sensitive (OMS) response by recording intracellularly from all classes of retinal interneurons while simultaneously recording the spiking output of many ganglion cells. Fast, transient bipolar cells respond linearly to motion in the receptive field center. The synaptic output from their terminals is rectified and then pooled by the OMS ganglion cell. A type of polyaxonal amacrine cell is driven by motion in the surround, again via pooling of rectified inputs, but from a different set of bipolar cell terminals. By direct intracellular current injection, we found that these polyaxonal amacrine cells selectively suppress the synaptic input of OMS ganglion cells. A quantitative model of these circuit elements and their interactions explains how an important visual computation is accomplished by retinal neurons and synapses.