Cell Receptive Fields Research Articles

Distinct subcomponents of mouse retinal ganglion cell receptive fields are differentially altered by light adaptation

The remarkable dynamic range of vision is facilitated by adaptation of retinal sensitivity to ambient lighting conditions. An important mechanism of sensitivity adaptation is control of the spatial and temporal window over which light is integrated. The retina accomplishes this by switching between parallel synaptic pathways with differing kinetics and degrees of synaptic convergence. However, the relative shifts in spatial and temporal integration are not well understood – particularly in the context of the antagonistic spatial surround. Here, we resolve these issues by characterizing the adaptation-induced changes to spatiotemporal integration in the linear receptive field center and surround of mouse retinal ganglion cells. While most ganglion cells lose their antagonistic spatial surround under scotopic conditions, a strong surround is maintained in a subset. We then applied a novel technique that allowed us to analyze the receptive field as a triphasic temporal filter in the center and a biphasic filter in the surround. The temporal tuning of the surround was relatively maintained across adaptation conditions compared to the center, which greatly increased its temporal integration. Though all phases of the center’s triphasic temporal response slowed, some shifted significantly less. Additionally, adaptation differentially shifted ON and OFF pathway temporal tuning, reducing their asymmetry under scotopic conditions. Finally, spatial integration was significantly increased by dark adaptation in some cells while it decreased it in others. These findings provide novel insight into how adaptation adjusts visual information processing by altering fundamental properties of ganglion cell receptive fields, such as center-surround antagonism and space-time integration.

Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive Somatotopic Representational Discontinuities and their Plasticity in a Computational Model of Primary Sensory Cortical Area 3b.

Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers), boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties.

Electrophysiological Method for Recording Intracellular Voltage Responses of <em>Drosophila</em> Photoreceptors and Interneurons to Light Stimuli <em>In Vivo</em>

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method described here enables the investigator to measure long-lasting (from minutes to hours) high-quality intracellular responses from single Drosophila R1-R6 photoreceptors and Large Monopolar Cells (LMCs) to light stimuli. Because the recording system has low noise, it can be used to study variability among individual cells in the fly eye, and how their outputs reflect the physical properties of the visual environment. We outline all key steps in performing this technique. The basic steps in constructing an appropriate electrophysiology set-up for recording, such as design and selection of the experimental equipment are described. We also explain how to prepare for recording by making appropriate (sharp) recording and (blunt) reference electrodes. Details are given on how to fix an intact fly in a bespoke fly-holder, prepare a small window in its eye and insert a recording electrode through this hole with minimal damage. We explain how to localize the center of a cell's receptive field, dark- or light-adapt the studied cell, and to record its voltage responses to dynamic light stimuli. Finally, we describe the criteria for stable normal recordings, show characteristic high-quality voltage responses of individual cells to different light stimuli, and briefly define how to quantify their signaling performance. Many aspects of the method are technically challenging and require practice and patience to master. But once learned and optimized for the investigator's experimental objectives, it grants outstanding in vivo neurophysiological data.

Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo.

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method described here enables the investigator to measure long-lasting (from minutes to hours) high-quality intracellular responses from single Drosophila R1-R6 photoreceptors and Large Monopolar Cells (LMCs) to light stimuli. Because the recording system has low noise, it can be used to study variability among individual cells in the fly eye, and how their outputs reflect the physical properties of the visual environment. We outline all key steps in performing this technique. The basic steps in constructing an appropriate electrophysiology set-up for recording, such as design and selection of the experimental equipment are described. We also explain how to prepare for recording by making appropriate (sharp) recording and (blunt) reference electrodes. Details are given on how to fix an intact fly in a bespoke fly-holder, prepare a small window in its eye and insert a recording electrode through this hole with minimal damage. We explain how to localize the center of a cell's receptive field, dark- or light-adapt the studied cell, and to record its voltage responses to dynamic light stimuli. Finally, we describe the criteria for stable normal recordings, show characteristic high-quality voltage responses of individual cells to different light stimuli, and briefly define how to quantify their signaling performance. Many aspects of the method are technically challenging and require practice and patience to master. But once learned and optimized for the investigator's experimental objectives, it grants outstanding in vivo neurophysiological data.

Commentary: Anatomical constitution of sense organs as a marker of mental disorders.

Commentary: Anatomical constitution of sense organs as a marker of mental disorders.

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina.

A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing.

Center-Surround Inhibition in Working Memory

Directing visual attention toward a particular feature or location in the environment suppresses processing of nearby stimuli [1-4]. Echoing the center-surround organization of retinal ganglion cell receptive fields [5], and biasing of competitive local neuronal dynamics in favor of task-relevant stimuli [6], this "inhibitory surround" attention mechanism accentuates the demarcation between task-relevant and irrelevant items. Here, we show that internally maintaining a color stimulus in working memory (WM), rather than visually attending the stimulus in the external environment, produces an analogous pattern of inhibition for stimuli that are nearby in color space. Replicating a well-known effect of attentional capture by stimuli that match WM content [7], visual attention was biased toward (task-irrelevant) stimuli that exactly matched a WM item. This bias was curtailed, however, for stimuli that were very similar to the WMcontent (i.e., within the inhibitory zone surrounding the focus of WM) and recovered for less similar stimuli (i.e., beyond the bounds of the inhibitory surround). Moreover, the expression of this inhibition effect was positively associated with WM performance across observers. In a second experiment, inhibition also occurred between two similar items simultaneously held in WM. This suggests that maintenance in WM is characterized by an excitatory peak centered on the focus of (internal) attention, surrounded by an inhibitory zone to limit interference by irrelevant and confusable representations. Here, thus, we show for the first time that the same center-surround selection mechanism that focuses visual attention on sensory stimuli also selectively maintains internally activated representations in WM.

The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene.

Spatial phase sensitivity of complex cells in primary visual cortex depends on stimulus contrast

Neurons in primary visual cortex are classified as simple, which are phase sensitive, or complex, which are significantly less phase sensitive. Previously, we have used drifting gratings to show that the phase sensitivity of complex cells increases at low contrast and after contrast adaptation while that of simple cells remains the same at all contrasts (Cloherty SL, Ibbotson MR. J Neurophysiol 113: 434-444, 2015; Crowder NA, van Kleef J, Dreher B, Ibbotson MR. J Neurophysiol 98: 1155-1166, 2007; van Kleef JP, Cloherty SL, Ibbotson MR. J Physiol 588: 3457-3470, 2010). However, drifting gratings confound the influence of spatial and temporal summation, so here we have stimulated complex cells with gratings that are spatially stationary but continuously reverse the polarity of the contrast over time (contrast-reversing gratings). By varying the spatial phase and contrast of the gratings we aimed to establish whether the contrast-dependent phase sensitivity of complex cells results from changes in spatial or temporal processing or both. We found that most of the increase in phase sensitivity at low contrasts could be attributed to changes in the spatial phase sensitivities of complex cells. However, at low contrasts the complex cells did not develop the spatiotemporal response characteristics of simple cells, in which paired response peaks occur 180° out of phase in time and space. Complex cells that increased their spatial phase sensitivity at low contrasts were significantly overrepresented in the supragranular layers of cortex. We conclude that complex cells in supragranular layers of cat cortex have dynamic spatial summation properties and that the mechanisms underlying complex cell receptive fields differ between cortical layers.

Functional properties of spontaneous excitatory currents and encoding of light/dark transitions in horizontal cells of the mouse retina.

As all visual information is represented in the spatio-temporal dynamics of transmitter release from photoreceptors and the combined postsynaptic responses of second-order neurons, appropriate synaptic transfer functions are fundamental for a meaningful perception of the visual world. The functional contribution of horizontal cells to gain control and organization of bipolar and ganglion cell receptive fields can only be evaluated with an in-depth understanding of signal processing in horizontal cells. Therefore, a horizontal slice preparation of the mouse retina was established to record from horizontal cell bodies with their dendritic fields intact and receiving functional synaptic input from cone photoreceptors. Horizontal cell bodies showed spontaneous excitatory currents (spEPSCs) of monophasic and more complex multi-peak waveforms. spEPSCs were induced by quantal release of glutamate from presynaptic cones with a unitary amplitude of 3 pA. Non-stationary noise analysis revealed that spEPSCs with a monoexponential decay were mediated by 7-8 glutamate receptors with a single-channel amplitude of 1.55 pA. Responses to photopic full-field illumination were characterized by reduction of a tonic inward current or hyperpolarization, inhibition of spEPSCs, followed by a fast and transient inward current at light offset. The response to periodic dark/light transitions of different frequencies was dependent on the adaptational status of the cell with a limiting frequency of 10 Hz. Both on and off components of the light response were mediated by AMPA and kainate receptors. Detailed analysis of horizontal cell synaptic physiology is a prerequisite for understanding signal coding and processing at the photoreceptor ribbon synapse.

Emergence of spatiotemporal invariance in large neuronal ensembles in rat barrel cortex.

Invariant sensory coding is the robust coding of some sensory information (e.g., stimulus type) despite major changes in other sensory parameters (e.g., stimulus strength). The contribution of large populations of neurons (ensembles) to invariant sensory coding is not well understood, but could offer distinct advantages over invariance in single cell receptive fields. To test invariant sensory coding in neuronal ensembles evoked by single whisker stimulation as early as primary sensory cortex, we recorded detailed spatiotemporal movies of evoked ensemble activity through the depth of rat barrel cortex using microelectrode arrays. We found that an emergent property of whisker evoked ensemble activity, its spatiotemporal profile, was notably invariant across major changes in stimulus amplitude (up to >200-fold). Such ensemble-based invariance was found for single whisker stimulation as well as for the integrated profile of activity evoked by the more naturalistic stimulation of the entire whisker array. Further, the integrated profile of whisker array evoked ensemble activity and its invariance to stimulus amplitude shares striking similarities to “funneled” tactile perception in humans. We therefore suggest that ensemble-based invariance could provide a robust neurobiological substrate for invariant sensory coding and integration at an early stage of cortical sensory processing already in primary sensory cortex.

Equation of motion and general solution for the one-dimensional complex cell response in the signal-tuned approach.

A signal-tuned approach has been recently introduced for modeling stimulus-dependent cortical receptive fields. The approach is based on signal-tuned Gabor functions, which are Gaussian-modulated sinusoids whose parameters are obtained from a "tuning" signal. Given a stimulus to a cell, it is taken as the tuning signal for the Gabor function modeling the cell's receptive field, and the inner product of the stimulus and the stimulus-dependent field produces the cell's response. Here, we derive and solve the equation of motion for the signal-tuned complex cell response r(x,τ), where x and τ are receptive-field parameters: its center, and the delay with which it adapts to a change in input. The motion equation can be mapped onto the Schrödinger equation for a system with time-dependent imaginary mass and time-dependent complex potential, and yields a plane-wave solution and an Airy-packet solution. The plane-wave solution replicates responses previously obtained for temporally modulated and translating signals, and yields responses which seem compatible with apparent-motion effects, when the stimulus is a pair of alternating pulses. The Airy-packet solution can lead to long-range propagating responses.

Letter identification and the neural image classifier.

Letter identification is an important visual task for both practical and theoretical reasons. To extend and test existing models, we have reviewed published data for contrast sensitivity for letter identification as a function of size and have also collected new data. Contrast sensitivity increases rapidly from the acuity limit but slows and asymptotes at a symbol size of about 1 degree. We recast these data in terms of contrast difference energy: the average of the squared distances between the letter images and the average letter image. In terms of sensitivity to contrast difference energy, and thus visual efficiency, there is a peak around ¼ degree, followed by a marked decline at larger sizes. These results are explained by a Neural Image Classifier model that includes optical filtering and retinal neural filtering, sampling, and noise, followed by an optimal classifier. As letters are enlarged, sensitivity declines because of the increasing size and spacing of the midget retinal ganglion cell receptive fields in the periphery.

Opposing motion inhibits responses of direction-selective ganglion cells in the fish retina.

Inhibitory influences in receptive fields (RFs) of the fish retinal direction-selective ganglion cells (DS GCs) were investigated. Responses of the fast retinal DS GCs were recorded extracellularly from their axon terminals in the superficial layer of tectum opticum of immobilized fish. The data were collected from two cyprinid species - Carassius gibelio, a wild form of the goldfish, and the barbel fish Labeobarbus intermedius. Visual stimuli were presented to the fish on the monitor screen within a square area of stimulation occupying approximately 11 × 11° of the visual field. DS GCs were stimulated by pairs of narrow stripes moving in opposing directions. One of them entered central (responsive) area of cell receptive field (RRF) from the preferred, and the other one from the null side. Stimuli merged at center of stimulation area, and subsequently moved away from each other. It was shown that the cell response evoked by the stripe coming from the preferred side of RF was inhibited by the stimulus coming from the opposite direction. In the majority of units recorded inhibitory effect induced by the null-side stimulus was initiated in the RF periphery. As a rule, inhibitory influences sent from the RF periphery were spread across the entire central area of RF. Modifications of the inhibitory influences were investigated throughout the whole motion of paired stimuli. Evident inhibitory effects mediated from the null direction were recorded during the approach of stimuli. When stripes crossed each other and moved apart inhibition was terminated, and cell response appeared again. Null-side inhibition observed in fish DS GCs is most likely induced by starburst-like amacrine cells described in morphological studies of different fish species. Possible mechanisms underlying direction selectivity in fish DS GCs are discussed.

Influence of environmental information in natural scenes and the effects of motion adaptation on a fly motion-sensitive neuron during simulated flight.

ABSTRACTGaining information about the spatial layout of natural scenes is a challenging task that flies need to solve, especially when moving at high velocities. A group of motion sensitive cells in the lobula plate of flies is supposed to represent information about self-motion as well as the environment. Relevant environmental features might be the nearness of structures, influencing retinal velocity during translational self-motion, and the brightness contrast. We recorded the responses of the H1 cell, an individually identifiable lobula plate tangential cell, during stimulation with image sequences, simulating translational motion through natural sceneries with a variety of differing depth structures. A correlation was found between the average nearness of environmental structures within large parts of the cell's receptive field and its response across a variety of scenes, but no correlation was found between the brightness contrast of the stimuli and the cell response. As a consequence of motion adaptation resulting from repeated translation through the environment, the time-dependent response modulations induced by the spatial structure of the environment were increased relatively to the background activity of the cell. These results support the hypothesis that some lobula plate tangential cells do not only serve as sensors of self-motion, but also as a part of a neural system that processes information about the spatial layout of natural scenes.

Temporal correlation mechanisms and their role in feature selection: a single-unit study in primate somatosensory cortex.

Author SummaryAttention can select stimuli in space based on the stimulus features most relevant for a task. Attention effects have been linked to several important phenomena such as modulations in neuronal spiking rate (i.e., the average number of spikes per unit time) and spike-spike synchrony between neurons. Attention has also been associated with spike count correlations, a measure that is thought to reflect correlated noise in the population of neurons. Here, we studied whether feature-based attention biases the correlated activity between neurons when attention is directed towards their common preferred feature. Simultaneous single-unit recordings were obtained from multiple neurons in secondary somatosensory cortex in non-human primates performing feature-attention tasks. Both firing rate and spike-synchrony were enhanced when attention was directed towards the preferred feature of cells. However, attention effects on spike-synchrony had a tighter relationship with behavior. Further, attention decreased spike-count correlations when it was directed towards the receptive field of cells. Our data indicate that temporal correlation codes play a role in mediating feature selection, and are consistent with a feature-based selection model that operates by reducing the overall noise in a population and synchronizing activity across subpopulations that encode the relevant features of sensory stimuli.

Local density of human midget retinal ganglion cell receptive fields

Local density of human midget retinal ganglion cell receptive fields

Second order receptive field properties of simple and complex cells support a new standard model of thalamocortical circuitry in V1.

[Hubel and Wiesel's (1962)][1] hierarchical model of simple and complex cell receptive fields (RFs) has shaped our understanding of the structure and function of the primary visual cortex (V1). They proposed that the characteristic elongated ON or OFF subregions of simple-cell RFs are constructed

A formula for human retinal ganglion cell receptive field density as a function of visual field location.

In the human eye, all visual information must traverse the retinal ganglion cells. The most numerous subclass, the midget retinal ganglion cells, are believed to underlie spatial pattern vision. Thus the density of their receptive fields imposes a fundamental limit on the spatial resolution of human vision. This density varies across the retina, declining rapidly with distance from the fovea. Modeling spatial vision of extended or peripheral targets thus requires a quantitative description of midget cell density throughout the visual field. Through an analysis of published data on human retinal topography of cones and ganglion cells, as well as analysis of prior formulas, we have developed a new formula for midget retinal ganglion cell density as a function of position in the monocular or binocular visual field.

Extracellular ATP hydrolysis inhibits synaptic transmission by increasing ph buffering in the synaptic cleft.

Author SummaryAt the first retinal synapse, specific cells—horizontal cells (HCs)—inhibit photoreceptors and help to organize the receptive fields of another retinal cell type, bipolar cells. This synaptic interaction is crucial for visual contrast enhancement. Here we show that horizontal cells feed back to photoreceptors via a very fast ephaptic mechanism and a relatively slow mechanism. The slow mechanism requires ATP release via Pannexin 1 (Panx1) channels that are located on HC dendrites near the site where photoreceptors release the neurotransmitter glutamate to HCs and bipolar cells. The released ATP is hydrolyzed to produce AMP, phosphate groups, and protons; these phosphates and protons form a pH buffer, which acidifies the synaptic cleft. This slow acidification inhibits presynaptic calcium channels and consequently reduces the neurotransmitter release of photoreceptors. This demonstrates a new way in which ATP release can be involved in synaptic modulation. Surprisingly, the action of ATP is not purinergic but is mediated via changes in the pH buffer capacity in the synaptic cleft. Given the broad expression of Panx1 channels in the nervous system and the suggestion that Panx1 function underlies stabilization of synaptic plasticity and is needed for learning, we anticipate that this mechanism will be more widespread than just occurring at the first retinal synapse.