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.

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 (

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 Offtype 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.multielectrode recording | computational modeling I n local neural circuits of the brain, interneurons change the output of the circuit by combining their own transmission with inputs to the circuit (1). Inhibitory interneurons throughout the brain have great diversity in their morphology, postsynaptic connections, and biochemistry, but for nearly all of these cells, their functional role in information processing is unknown. In the retina, inhibitory amacrine cells comprise more than 30 classes; most of these cells also have unknown function (2, 3).Compared with a principal neuron, which represents a circuit's output, understanding the functional role of interneurons is a challenge because the effect of an interneuron on the circuit's output is a combination of multiple circuit properties (4, 5). For example, the effect of an amacrine cell on a retinal ganglion cell is a function of the amacrine cell's light response, its effects of transmission on the retinal ganglion cell, and of other visual input to the ganglion cell. Knowledge of all three of these properties is needed to predict how the amacrine cell will affect the ganglion cell's activity.The responses of different cells are precisely timed in the retina, with different amacrine and ganglion cells having distinct temporal responses with respect to light (6-9). Inhibitory transmission to ganglion cells is known to have different effects, i...

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.