Salamander Retina Research Articles

Linear and Nonlinear Behaviors of the Photoreceptor Coupled Network.

Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study, we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to eight cells and to determine the electrical connectivity among multiple rods. We found direct evidence that voltage signal spread in the rod-rod coupling network in the absence of I h (mediated by HCN channels) is passive and follows the linear cable equation. Under physiological conditions, I h shapes the network signal by progressively shortening the response time-to-peak of distant rods, compensating the time loss of signal traveling from distant rods to bipolar cell somas and facilitating synchronization of rod output signals. Under voltage-clamp conditions, current flow within the coupled rods follows Ohm's law, supporting the idea that nonlinear behaviors of the rod network are dependent on membrane voltage. Rod-rod coupling is largely symmetrical in the 2D array, and voltage-clamp blocking the next neighboring rod largely suppresses rod signal spread into the second neighboring rod, suggesting that indirect coupling pathways play a minor role in rod-rod coupling.

Antagonistic surround responses in different cones are mediated by feedback synapses from different horizontal cells

Cone photoreceptors are the first neurons along the visual pathway that exhibit center-surround antagonistic receptive fields, the basic building blocks for spatial information processing in the visual system. The surround responses in cones are mediated by the horizontal cells (HCs) via multiple feedback synaptic mechanisms. It has been controversial on which mechanisms are responsible for the surround-elicited depolarizing responses in cones (ΔVCone(s)), and whether the surround responses of various types of cones are mediated by the same HC feedback mechanisms. In this report, we studied ΔVCone(s)) of four types of cones in the salamander retina, and found that they are mediated by feedback synapses from A-type, B-type or A- and B-type HCs. ΔVCone(s) are observable in the presence of concomitant center light spots, and surround + center light stimuli of various intensity, size and wavelength differentially activate the feedback synapses from A- and B-type HCs to cones. We found that ΔVCone(s) of the L-cones are mediated by both A- and B-type HCs, those of the P- and S-cones by B-type HCs, and those of the A-cones by the A-type HCs. Moreover, our results suggest that B-type HCs mediate ΔVCone(s) through both GABAergic and GluT-ClC feedback synaptic mechanisms, and A-type HCs mediate ΔVCone(s) via the GluT-ClC feedback mechanism. Feedback synaptic mechanisms that increase calcium influx in cone synaptic terminals play important roles in mediating the antagonistic surround responses in the postsynaptic bipolar cells, but they may not generate enough current to depolarize the cones and significantly contribute to ΔVCone(s).

Nonlinear spatial integration in retinal bipolar cells shapes the encoding of artificial and natural stimuli

SummaryThe retina dissects the visual scene into parallel information channels, which extract specific visual features through nonlinear processing. The first nonlinear stage is typically considered to occur at the output of bipolar cells, resulting from nonlinear transmitter release from synaptic terminals. In contrast, we show here that bipolar cells themselves can act as nonlinear processing elements at the level of their somatic membrane potential. Intracellular recordings from bipolar cells in the salamander retina revealed frequent nonlinear integration of visual signals within bipolar cell receptive field centers, affecting the encoding of artificial and natural stimuli. These nonlinearities provide sensitivity to spatial structure below the scale of bipolar cell receptive fields in both bipolar and downstream ganglion cells and appear to arise at the excitatory input into bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought: that is, at the input stage of bipolar cells.

Transmission at rod and cone ribbon synapses in the retina.

Light-evoked voltage responses of rod and cone photoreceptor cells in the vertebrate retina must be converted to a train of synaptic vesicle release events for transmission to downstream neurons. This review discusses the processes, proteins, and structures that shape this critical early step in vision, focusing on studies from salamander retina with comparisons to other experimental animals. Many mechanisms are conserved across species. In cones, glutamate release is confined to ribbon release sites although rods are also capable of release at non-ribbon sites. The role of non-ribbon release in rods remains unclear. Release from synaptic ribbons in rods and cones involves at least three vesicle pools: a readily releasable pool (RRP) matching the number of membrane-associated vesicles along the ribbon base, a ribbon reserve pool matching the number of additional vesicles on the ribbon, and an enormous cytoplasmic reserve. Vesicle release increases in parallel with Ca2+ channel activity. While the opening of only a few Ca2+ channels beneath each ribbon can trigger fusion of a single vesicle, sustained release rates in darkness are governed by the rate at which the RRP can be replenished. The number of vacant release sites, their functional status, and the rate of vesicle delivery in turn govern replenishment. Along with an overview of the mechanisms of exocytosis and endocytosis, we consider specific properties of ribbon-associated proteins and pose a number of remaining questions about this first synapse in the visual system.

ATP-mediated increase in H+ flux from retinal Müller cells: a role for Na+/H+ exchange.

Small alterations in extracellular H+ can profoundly alter neurotransmitter release by neurons. We examined mechanisms by which extracellular ATP induces an extracellular H+ flux from Müller glial cells, which surround synaptic connections throughout the vertebrate retina. Müller glia were isolated from tiger salamander retinae and H+ fluxes examined using self-referencing H+-selective microelectrodes. Experiments were performed in 1 mM HEPES with no bicarbonate present. Replacement of extracellular sodium by choline decreased H+ efflux induced by 10 µM ATP by 75%. ATP-induced H+ efflux was also reduced by Na+/H+ exchange inhibitors. Amiloride reduced H+ efflux initiated by 10 µM ATP by 60%, while 10 µM cariporide decreased H+ flux by 37%, and 25 µM zoniporide reduced H+ flux by 32%. ATP-induced H+ fluxes were not significantly altered by the K+/H+ pump blockers SCH28080 or TAK438, and replacement of all extracellular chloride with gluconate was without effect on H+ fluxes. Recordings of ATP-induced H+ efflux from cells that were simultaneously whole cell voltage clamped revealed no effect of membrane potential from -70 mV to 0 mV. Restoration of extracellular potassium after cells were bathed in 0 mM potassium produced a transient alteration in ATP-dependent H+ efflux. The transient response to extracellular potassium occurred only when extracellular sodium was present and was abolished by 1 mM ouabain, suggesting that alterations in sodium gradients were mediated by Na+/K+-ATPase activity. Our data indicate that the majority of H+ efflux elicited by extracellular ATP from isolated Müller cells is mediated by Na+/H+ exchange.NEW & NOTEWORTHY Glial cells are known to regulate neuronal activity, but the exact mechanism(s) whereby these "support" cells modulate synaptic transmission remains unclear. Small changes in extracellular levels of acidity are known to be particularly powerful regulators of neurotransmitter release. Here, we show that extracellular ATP, known to be a potent activator of glial cells, induces H+ efflux from retinal Müller (glial) cells and that the bulk of the H+ efflux is mediated by Na+/H+ exchange.

Interspike intervals within retinal spike bursts combinatorially encode multiple stimulus features.

Neurons in various regions of the brain generate spike bursts. While the number of spikes within a burst has been shown to carry information, information coding by interspike intervals (ISIs) is less well understood. In particular, a burst with k spikes has k-1 intraburst ISIs, and these k-1 ISIs could theoretically encode k-1 independent values. In this study, we demonstrate that such combinatorial coding occurs for retinal bursts. By recording ganglion cell spikes from isolated salamander retinae, we found that intraburst ISIs encode oscillatory light sequences that are much faster than the light intensity modulation encoded by the number of spikes. When a burst has three spikes, the two intraburst ISIs combinatorially encode the amplitude and phase of the oscillatory sequence. Analysis of trial-to-trial variability suggested that intraburst ISIs are regulated by two independent mechanisms responding to orthogonal oscillatory components, one of which is common to bursts with a different number of spikes. Therefore, the retina encodes multiple stimulus features by exploiting all degrees of freedom of burst spike patterns, i.e., the spike number and multiple intraburst ISIs.

Contributions of glutamate transporters and Ca2+-activated Cl− currents to feedback from horizontal cells to cone photoreceptors

Lateral inhibitory feedback from horizontal cells (HCs) to cones establishes center-surround receptive fields and color opponency in the retina. When HCs hyperpolarize to light, inhibitory feedback to cones increases activation of cone Ca2+ currents (ICa) that can in turn activate additional currents. We recorded simultaneously from cones and HCs to analyze cone currents activated by HC feedback in salamander retina. Depolarization-activated inward tail currents in cones were inhibited by CaCCinh-A01 that inhibits both Ano1 and Ano2 Ca2+-activated Cl− currents (ICl(Ca)). An Ano1-selective inhibitor Ani9 was less effective suggesting that Ano2 is the predominant ICl(Ca) subtype in cones. CaCCinh-A01 inhibited feedback currents more strongly when intracellular Ca2+ in cones was buffered with 0.05 mM EGTA compared to stronger buffering with 5 mM EGTA. By contrast, blocking glutamate transporter anion currents (ICl(Glu)) with TBOA had stronger inhibitory effects on cone feedback currents when Ca2+ buffering was strong. Inward feedback currents ran down at rates intermediate between rundown of glutamate release and ICl(Ca), consistent with contributions to feedback from both ICl(Ca) and ICl(Glu). These results suggest that Cl− channels coupled to glutamate transporters help to speed inward feedback currents initiated by local changes in intracellular [Ca2+] close to synaptic ribbons of cones whereas Ano2 Ca2+-activated Cl− channels contribute to slower components of feedback regulated by spatially extensive changes in intracellular [Ca2+].

Adaptation of Inhibition Mediates Retinal Sensitization

In response to a changing sensory environment, sensory systems adjust their neural code for a number of purposes, including an enhanced sensitivity for novel stimuli, prediction of sensory features, and the maintenance of sensitivity. Retinal sensitization is a form of short-term plasticity that elevates local sensitivity following strong, local, visual stimulation and has been shown to create a prediction of the presence of a nearby localized object. The neural mechanism that generates this elevation in sensitivity remains unknown. Using simultaneous intracellular and multielectrode recording in the salamander retina, we show that a decrease in tonic amacrine transmission is necessary for and is correlated spatially and temporally with ganglion cell sensitization. Furthermore, introducing a decrease in amacrine transmission is sufficient to sensitize nearby ganglion cells. A computational model accounting for adaptive dynamics and nonlinear pathways confirms a decrease in steady inhibitory transmission can cause sensitization. Adaptation of inhibition enhances the sensitivity to the sensory feature conveyed by an inhibitory pathway, creating a prediction of future input.

Radiation Force as a Physical Mechanism for Ultrasonic Neurostimulation of the Ex Vivo Retina.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5-43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects.SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Actin Dynamics, Regulated by RhoA-LIMK-Cofilin Signaling, Mediates Rod Photoreceptor Axonal Retraction After Retinal Injury.

PurposeRetraction of the axon terminals of rod photoreceptors after retinal detachment breaks the first synapse in the visual pathway, resulting in visual impairment. Previous work showed that the mechanism of axonal retraction involves RhoA signaling and its downstream effector LIM Kinase (LIMK) activation. We examined the response of the downstream component cofilin, a direct binding protein of actin filaments, as well as the regulation by RhoA-LIMK-Cofilin signaling of actin assembly/disassembly, in the presynaptic ribbon terminal of injured rod cells.MethodsInjury was produced by retinal detachment or rod cell isolation. Detached porcine retina was probed for levels and localization of phosphorylated cofilin with Western blots and confocal microscopy, whereas rod cell cultures of dissociated salamander retina were examined for filamentous actin assembly/disassembly with a barbed end assay and phalloidin staining.ResultsA detachment increased phosphorylation of cofilin in retinal explants; phosphorylation occurred in rod terminals in sections of detached retina. Isolation of rod cells resulted in axon retraction accompanied by an increase in actin barbed ends and a decrease in net filament labeling. All changes were significantly reduced by either Rho kinase (ROCK) or LIMK inhibition, using Y27632 or BMS-5, respectively. Cytochalasin D also reduced retraction and stabilized filaments in isolated rod cells.ConclusionsThese results indicate that actin depolymerization via activation of RhoA downstream kinases and cofilin contributes to axon retraction. Preventing depolymerization, in addition to actomyosin contraction, may stabilize ribbon synapses after trauma.

Data-driven inference of hidden nodes in networks

The explosion of activity in finding interactions in complex systems is driven by availability of copious observations of complex natural systems. However, such systems, e.g., the human brain, are rarely completely observable. Interaction network inference must then contend with hidden variables affecting the behavior of the observed parts of the system. We present an effective approach for model inference with hidden variables. From configurations of observed variables, we identify the observed-to-observed, hidden-to-observed, observed-to-hidden, and hidden-to-hidden interactions, the configurations of hidden variables, and the number of hidden variables. We demonstrate the performance of our method by simulating a kinetic Ising model, and show that our method outperforms existing methods. Turning to real data, we infer the hidden nodes in a neuronal network in the salamander retina and a stock market network. We show that predictive modeling with hidden variables is significantly more accurate than that without hidden variables. Finally, an important hidden variable problem is to find the number of clusters in a dataset. We apply our method to classify MNIST handwritten digits. We find that there are about 60 clusters which are roughly equally distributed among the digits.

Network inference in stochastic systems from neurons to currencies: Improved performance at small sample size.

The fundamental problem in modeling complex phenomena such as human perception using probabilistic methods is that of deducing a stochastic model of interactions between the constituents of a system from observed configurations. Even in this era of big data, the complexity of the systems being modeled implies that inference methods must be effective in the difficult regimes of small sample sizes and large coupling variability. Thus, model inference by means of minimization of a cost function requires additional assumptions such as sparsity of interactions to avoid overfitting. In this paper, we completely divorce iterative model updates from the value of a cost function quantifying goodness of fit. This separation enables the use of goodness of fit as a natural rationale for terminating model updates, thereby avoiding overfitting. We do this within the mathematical formalism of statistical physics by defining a formal free energy of observations from a partition function with an energy function chosen precisely to enable an iterative model update. Minimizing this free energy, we demonstrate coupling strength inference in nonequilibrium kinetic Ising models, and show that our method outperforms other existing methods in the regimes of interest. Our method has no tunable learning rate, scales to large system sizes, and has a systematic expansion to obtain higher-order interactions. As applications, we infer a functional connectivity network in the salamander retina and a currency exchange rate network from time-series data of neuronal spiking and currency exchange rates, respectively. Accurate small sample size inference is critical for devising a profitable currency hedging strategy.

Activity Correlations between Direction-Selective Retinal Ganglion Cells Synergistically Enhance Motion Decoding from Complex Visual Scenes

SummaryNeurons in sensory systems are often tuned to particular stimulus features. During complex naturalistic stimulation, however, multiple features may simultaneously affect neuronal responses, which complicates the readout of individual features. To investigate feature representation under complex stimulation, we studied how direction-selective ganglion cells in salamander retina respond to texture motion where direction, velocity, and spatial pattern inside the receptive field continuously change. We found that the cells preserve their direction preference under this stimulation, yet their direction encoding becomes ambiguous due to simultaneous activation by luminance changes. The ambiguities can be resolved by considering populations of direction-selective cells with different preferred directions. This gives rise to synergistic motion decoding, yielding more information from the population than the summed information from single-cell responses. Strong positive response correlations between cells with different preferred directions amplify this synergy. Our results show how correlated population activity can enhance feature extraction in complex visual scenes.

A single retinal circuit model for multiple computations.

Vision is dependent on extracting intricate features of the visual information from the outside world, and complex visual computations begin to take place as soon as at the retinal level. In multiple studies on salamander retinas, the responses of a subtype of retinal ganglion cells, i.e., fast/biphasic-OFF ganglion cells, have been shown to be able to realize multiple functions, such as the segregation of a moving object from its background, motion anticipation, and rapid encoding of the spatial features of a new visual scene. For each of these visual functions, modeling approaches using extended linear-nonlinear cascade models suggest specific preceding retinal circuitries merging onto fast/biphasic-OFF ganglion cells. However, whether multiple visual functions can be accommodated together in a certain retinal circuitry and how specific mechanisms for each visual function interact with each other have not been investigated. Here, we propose a physiologically consistent, detailed computational model of the retinal circuit based on the spatiotemporal dynamics and connections of each class of retinal neurons to implement object motion sensitivity, motion anticipation, and rapid coding in the same circuit. Simulations suggest that multiple computations can be accommodated together, thereby implying that the fast/biphasic-OFF ganglion cell has potential to output a train of spikes carrying multiple pieces of information on distinct features of the visual stimuli.

Learning to make external sensory stimulus predictions using internal correlations in populations of neurons

To compensate for sensory processing delays, the visual system must make predictions to ensure timely and appropriate behaviors. Recent work has found predictive information about the stimulus in neural populations early in vision processing, starting in the retina. However, to utilize this information, cells downstream must be able to read out the predictive information from the spiking activity of retinal ganglion cells. Here we investigate whether a downstream cell could learn efficient encoding of predictive information in its inputs from the correlations in the inputs themselves, in the absence of other instructive signals. We simulate learning driven by spiking activity recorded in salamander retina. We model a downstream cell as a binary neuron receiving a small group of weighted inputs and quantify the predictive information between activity in the binary neuron and future input. Input weights change according to spike timing-dependent learning rules during a training period. We characterize the readouts learned under spike timing-dependent synaptic update rules, finding that although the fixed points of learning dynamics are not associated with absolute optimal readouts they convey nearly all of the information conveyed by the optimal readout. Moreover, we find that learned perceptrons transmit position and velocity information of a moving-bar stimulus nearly as efficiently as optimal perceptrons. We conclude that predictive information is, in principle, readable from the perspective of downstream neurons in the absence of other inputs. This suggests an important role for feedforward prediction in sensory encoding.

Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes.

Self-referencing H+-selective electrodes were used to measure extracellular H+ fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H+-selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H+ flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H+ flux. Barium at 6 mM also increased H+ flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 μM DIDS, 300 μM SITS, and 30 μM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 μM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H+ fluxes, and removal of the end foot region further decreased the H+ flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H+-selective electrodes can be used to monitor H+ fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell.NEW & NOTEWORTHY The present study uses self-referencing H+-selective electrodes for the first time to measure H+ fluxes from Müller (glial) cells isolated from tiger salamander retina. These studies demonstrate bicarbonate transport as a potent regulator of extracellular levels of acidity around Müller cells and point toward a need for further studies aimed at addressing how such glial cell pH regulatory mechanisms may shape neuronal signaling.

Inference of neuronal functional circuitry with spike-triggered non-negative matrix factorization

Neurons in sensory systems often pool inputs over arrays of presynaptic cells, giving rise to functional subunits inside a neuron’s receptive field. The organization of these subunits provides a signature of the neuron’s presynaptic functional connectivity and determines how the neuron integrates sensory stimuli. Here we introduce the method of spike-triggered non-negative matrix factorization for detecting the layout of subunits within a neuron’s receptive field. The method only requires the neuron’s spiking responses under finely structured sensory stimulation and is therefore applicable to large populations of simultaneously recorded neurons. Applied to recordings from ganglion cells in the salamander retina, the method retrieves the receptive fields of presynaptic bipolar cells, as verified by simultaneous bipolar and ganglion cell recordings. The identified subunit layouts allow improved predictions of ganglion cell responses to natural stimuli and reveal shared bipolar cell input into distinct types of ganglion cells.

A Presynaptic Group III mGluR Recruits Gβγ/SNARE Interactions to Inhibit Synaptic Transmission by Cone Photoreceptors in the Vertebrate Retina.

G-protein βγ subunits (Gβγ) interact with presynaptic proteins and regulate neurotransmitter release downstream of Ca2+ influx. To accomplish their roles in sensory signaling, photoreceptor synapses use specialized presynaptic proteins that support neurotransmission at active zone structures known as ribbons. While several G-protein coupled receptors (GPCRs) influence synaptic transmission at ribbon synapses of cones and other retinal neurons, it is unknown whether Gβγ contributes to these effects. We tested whether activation of one particular GPCR, a metabotropic glutamate receptor (mGluR), can reduce cone synaptic transmission via Gβγ in tiger salamander retinas. In recordings from horizontal cells, we found that an mGluR agonist (L-AP4) reduced cone-driven light responses and mEPSC frequency. In paired recordings of cones and horizontal cells, L-AP4 slightly reduced cone ICa (∼10%) and caused a larger reduction in cone-driven EPSCs (∼30%). Proximity ligation assay revealed direct interactions between SNAP-25 and Gβγ subunits in retinal synaptic layers. Pretreatment with the SNAP-25 cleaving protease BoNT/A inhibited L-AP4 effects on synaptic transmission, as did introduction of a peptide derived from the SNAP-25 C terminus. Introducing Gβγ subunits directly into cones reduced EPSC amplitude. This effect was inhibited by BoNT/A, supporting a role for Gβγ/SNAP-25 interactions. However, the mGluR-dependent reduction in ICa was not mimicked by Gβγ, indicating that this effect was independent of Gβγ. The finding that synaptic transmission at cone ribbon synapses is regulated by Gβγ/SNAP-25 interactions indicates that these mechanisms are shared by conventional and ribbon-type synapses. Gβγ liberated from other photoreceptor GPCRs is also likely to regulate synaptic transmission.SIGNIFICANCE STATEMENT Dynamic regulation of synaptic transmission by presynaptic G-protein coupled receptors shapes information flow through neural circuits. At the first synapse in the visual system, presynaptic metabotropic glutamate receptors (mGluRs) regulate cone photoreceptor synaptic transmission, although the mechanisms and functional impact of this are unclear. We show that mGluRs regulate light response encoding across the cone synapse, accomplished in part by triggering G-protein βγ subunits (Gβγ) interactions with SNAP-25, a core component of the synaptic vesicle fusion machinery. In addition to revealing a role in visual processing, this provides the first demonstration that Gβγ/SNAP-25 interactions regulate synaptic function at a ribbon-type synapse, contributing to an emerging picture of the ubiquity of Gβγ/SNARE interactions in regulating synaptic transmission throughout the nervous system.

Joint Encoding of Object Motion and Motion Direction in the Salamander Retina.

The retina contains specialized cells for motion processing. Among the retinal ganglion cells, which form the output neurons of the retina, some are known to report the direction of a moving stimulus (direction-selective cells), and others distinguish the motion of an object from a moving background. But little is known about how information about local object motion and information about motion direction interact. Here, we report that direction-selective ganglion cells can be identified in the salamander retina, where their existence had been unclear. Furthermore, there are two independent systems of direction-selective cells, and one of these combines direction selectivity with sensitivity to local motion. The output of these cells could assist in tracking moving objects and estimating their future position.

Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains.

Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations), in their temporal dimension (temporal neural response variations), or in their combination (temporally coordinated neural population firing). Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together), temporal firing patterns (temporal activation of these groups of neurons) and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial). We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine-scale image features, and supplied almost as much information about coarse natural image features as firing rates. Together, these results highlight the importance of spike timing, and particularly of first-spike latencies, in retinal coding.