Direction selectivity represents a fundamental visual computation. In mammalian retina, On-Off direction-selective ganglion cells (DSGCs) respond strongly to motion in a preferred direction and weakly to motion in the opposite, null direction. Electrical recordings suggested three direction-selective (DS) synaptic mechanisms: DS GABA release during null-direction motion from starburst amacrine cells (SACs) and DS acetylcholine and glutamate release during preferred direction motion from SACs and bipolar cells. However, evidence for DS acetylcholine and glutamate release has been inconsistent and at least one bipolar cell type that contacts another DSGC (On-type) lacks DS release. Here, whole-cell recordings in mouse retina showed that cholinergic input to On-Off DSGCs lacked DS, whereas the remaining (glutamatergic) input showed apparent DS. Fluorescence measurements with the glutamate biosensor intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) conditionally expressed in On-Off DSGCs showed that glutamate release in both On- and Off-layer dendrites lacked DS, whereas simultaneously recorded excitatory currents showed apparent DS. With GABA-A receptors blocked, both iGluSnFR signals and excitatory currents lacked DS. Our measurements rule out DS release from bipolar cells onto On-Off DSGCs and support a theoretical model suggesting that apparent DS excitation in voltage-clamp recordings results from inadequate voltage control of DSGC dendrites during null-direction inhibition. SAC GABA release is the apparent sole source of DS input onto On-Off DSGCs.

A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

The complexity of sensory receptive fields increases from one synaptic stage to the next. In many cases, increased complexity is achieved through spatiotemporal interactions between convergent excitatory and inhibitory inputs. Here, we present evidence that direction selectivity (DS), a complex emergent receptive field property of retinal starburst amacrine cells (SACs), is generated by spatiotemporal interactions between functionally diverse excitatory inputs. Electrophysiological whole-cell recordings from ON and OFF SACs show distinct temporal differences in excitation following proximal compared with distal stimulation of their receptive fields. Distal excitation is both faster and more transient, ruling out passive filtering by the dendrites and indicating a task-specific specialization. Model simulations demonstrate that this specific organization of excitation generates robust DS responses in SACs, consistent with elementary motion detector models. These results indicate that selective integration of spatiotemporally patterned excitation is a computational mechanism for motion detection in the mammalian retina.

Sensorimotor delays decouple behaviors from the events that drive them. The brain compensates for these delays with predictive mechanisms, but the efficacy and timescale over which these mechanisms operate remain poorly understood. Here, we assess how prediction is used to compensate for prey movement that occurs during visuomotor processing. We obtained high-speed video records of freely moving, tongue-projecting salamanders catching walking prey, emulating natural foraging conditions. We found that tongue projections were preceded by a rapid head turn lasting ∼130 ms. This motor lag, combined with the ∼100 ms phototransduction delay at photopic light levels, gave a ∼230 ms visuomotor response delay during which prey typically moved approximately one body length. Tongue projections, however, did not significantly lag prey position but were highly accurate instead. Angular errors in tongue projection accuracy were consistent with a linear extrapolation model that predicted prey position at the time of tongue contact using the average prey motion during a ∼175 ms period one visual latency before the head movement. The model explained successful strikes where the tongue hit the fly, and unsuccessful strikes where the fly turned and the tongue hit a phantom location consistent with the fly's earlier trajectory. The model parameters, obtained from the data, agree with the temporal integration and latency of retinal responses proposed to contribute to motion extrapolation. These results show that the salamander predicts future prey position and that prediction significantly improves prey capture success over a broad range of prey speeds and light levels.SIGNIFICANCE STATEMENTNeural processing delays cause actions to lag behind the events that elicit them. To cope with these delays, the brain predicts what will happen in the future. While neural circuits in the retina and beyond have been suggested to participate in such predictions, few behaviors have been explored sufficiently to constrain circuit function. Here we show that salamanders aim their tongues by using extrapolation to estimate future prey position, thereby compensating for internal delays from both visual and motor processing. Predictions made just before a prey turn resulted in the tongue being projected to a position consistent with the prey's pre-turn trajectory. These results define the computations and operating regimen for neural circuits that predict target motion.