Irregularly timed electrical pulses reduce adaptation of retinal ganglion cells.

OBJECTIVE: Retinal prostheses aim to provide visual percepts to blind people affected by diseases caused by photoreceptor degeneration. One of the main challenges presented by current devices is neural adaptation in the retina, which is believed to be the cause of fading-an effect where artificially produced percepts disappear over a short period of time, despite continuous stimulation of the retina. We aim to understand the neural adaptation generated in retinal ganglion cells (RGCs) during electrical stimulation. APPROACH: Current visual prostheses use electrical pulses with fixed frequencies and amplitudes modulated over hundreds of milliseconds to stimulate the retina. However, in nature, neuronal spiking occurs with stochastic timing, hence the information received naturally from other neurons by RGCs is irregularly timed. We used a single epiretinal electrode to stimulate and compare rat RGC responses to stimulus trains of biphasic pulses delivered at regular and random inter-pulse intervals (IPI), the latter taken from an exponential distribution. MAIN RESULTS: Our observations suggest that stimulation with random IPIs result in lower adaptation rates than stimulation with constant IPIs at frequencies of 50 Hz and 200 Hz. We also found a high proportion of lower amplitude action potentials, or spikelets. The spikelets were more prominent at high stimulation frequencies (50 Hz and 200 Hz) and were less susceptible to adaptation, but it was not clear if they propagated along the axon. SIGNIFICANCE: Using random IPI stimulation in retinal prostheses reduces the decay of RGCs and this could potentially reduce fading of electrically induced visual perception.

Neural basis of forward flight control and landing in honeybees.

The impressive repertoire of honeybee visually guided behaviors, and their ability to learn has made them an important tool for elucidating the visual basis of behavior. Like other insects, bees perform optomotor course correction to optic flow, a response that is dependent on the spatial structure of the visual environment. However, bees can also distinguish the speed of image motion during forward flight and landing, as well as estimate flight distances (odometry), irrespective of the visual scene. The neural pathways underlying these abilities are unknown. Here we report on a cluster of descending neurons (DNIIIs) that are shown to have the directional tuning properties necessary for detecting image motion during forward flight and landing on vertical surfaces. They have stable firing rates during prolonged periods of stimulation and respond to a wide range of image speeds, making them suitable to detect image flow during flight behaviors. While their responses are not strictly speed tuned, the shape and amplitudes of their speed tuning functions are resistant to large changes in spatial frequency. These cells are prime candidates not only for the control of flight speed and landing, but also the basis of a neural 'front end' of the honeybee's visual odometer.

Visual Neuroscience: Unique Neural System for Flight Stabilization in Hummingbirds.

The pretectal visual motion processing area in the hummingbird brain is unlike that in other birds: instead of emphasizing detection of horizontal movements, it codes for motion in all directions through 360°, possibly offering precise visual stability control during hovering.

Retinal ganglion cells: mechanisms underlying depolarization block and differential responses to high frequency electrical stimulation of ON and OFF cells.

OBJECTIVE: ON and OFF retinal ganglion cells (RGCs) are known to have non-monotonic responses to increasing amplitudes of high frequency (2 kHz) biphasic electrical stimulation. That is, an increase in stimulation amplitude causes an increase in the cell's spike rate up to a peak value above which further increases in stimulation amplitude cause the cell to decrease its activity. The peak response for ON and OFF cells occurs at different stimulation amplitudes, which allows differential stimulation of these functional cell types. In this study, we investigate the mechanisms underlying the non-monotonic responses of ON and OFF brisk-transient RGCs and the mechanisms underlying their differential responses. APPROACH: Using in vitro patch-clamp recordings from rat RGCs, together with simulations of single and multiple compartment Hodgkin-Huxley models, we show that the non-monotonic response to increasing amplitudes of stimulation is due to depolarization block, a change in the membrane potential that prevents the cell from generating action potentials. MAIN RESULTS: We show that the onset for depolarization block depends on the amplitude and frequency of stimulation and reveal the biophysical mechanisms that lead to depolarization block during high frequency stimulation. Our results indicate that differences in transmembrane potassium conductance lead to shifts of the stimulus currents that generate peak spike rates, suggesting that the differential responses of ON and OFF cells may be due to differences in the expression of this current type. We also show that the length of the axon's high sodium channel band (SOCB) affects non-monotonic responses and the stimulation amplitude that leads to the peak spike rate, suggesting that the length of the SOCB is shorter in ON cells. SIGNIFICANCE: This may have important implications for stimulation strategies in visual prostheses.

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.

Optimizing the electrical stimulation of retinal ganglion cells.

Epiretinal prostheses aim to restore visual perception in the blind through electrical stimulation of surviving retinal ganglion cells (RGCs). While the effects of several waveform parameters (e.g., phase duration) on stimulation efficacy have been described, their relative influence remains unclear. Further, morphological differences between RGC classes represent a key source of variability that has not been accounted for in previous studies. Here we investigate the effect of electrical stimulus waveform parameters on activation of an anatomically homogenous RGC population and describe a technique for identifying optimal stimulus parameters to minimize the required stimulus charge. Responses of rat A2-type RGCs to a broad array of biphasic stimulation parameters, delivered via an epiretinal stimulating electrode (200 × 200 µ m) were recorded using whole-cell current clamp techniques. The data demonstrate that for rectangular charge-balanced stimuli, phase duration and polarity have the largest effect on threshold current amplitude-cells were most responsive to cathodic-first pulses of short phase duration. Waveform asymmetry and increases in interphase interval further reduced thresholds. Using optimal waveform parameters, we observed a drop in stimulus efficacy with increasing stimulation frequency. This was more pronounced for large cells. Our results demonstrate that careful choice of electrical waveform parameters can significantly improve the efficacy of electrical stimulation and the efficacy of implantable neurostimulators for the retina.

Phase sensitivity of complex cells in primary visual cortex.

Neurons in the primary visual cortex are often classified as either simple or complex based on the linearity (or otherwise) of their response to spatial luminance contrast. In practice, classification is typically based on Fourier analysis of a cell's response to an optimal drifting sine-wave grating. Simple cells are generally considered to be linear and produce responses modulated at the fundamental frequency of the stimulus grating. In contrast, complex cells exhibit significant nonlinearities that reduce the response at the fundamental frequency. Cells can therefore be easily and objectively classified based on the relative modulation of their responses - the ratio of the phase-sensitive response at the fundamental frequency of the stimulus (F1) to the phase-invariant sustained response (F0). Cells are classified as simple if F1/F0>1 and complex if F1/F0<1. This classification is broadly consistent with criteria based on the spatial organisation of cells' receptive fields and is accordingly presumed to reflect disparate functional roles of simple and complex cells in coding visual information. However, Fourier analysis of spiking responses is sensitive to the number of spikes available - F1/F0 increases as the number of spikes is reduced, even for phase-invariant complex cells. Moreover, many complex cells encountered in the laboratory exhibit some phase sensitivity, evident as modulation of their responses at the fundamental frequency. There currently exists no objective quantitative means of assessing the significance or otherwise of these modulations. Here we derive a statistical basis for objectively assessing whether the modulation of neuronal responses is reliable, thereby adding a level of statistical certainty to measures of phase sensitivity. We apply our statistical analysis to neuronal responses to moving sine-wave gratings recorded from 367 cells in cat primary visual cortex. We find that approximately 60% of complex cells exhibit statistically significant (α<0.01) modulation of their responses to optimal moving gratings. These complex cells are phase sensitive and reliably encode spatial phase.

Spectral inputs and ocellar contributions to a pitch-sensitive descending neuron in the honeybee.

By measuring insect compensatory optomotor reflexes to visual motion, researchers have examined the computational mechanisms of the motion processing system. However, establishing the spectral sensitivity of the neural pathways that underlie this motion behavior has been difficult, and the contribution of the simple eyes (ocelli) has been rarely examined. In this study we investigate the spectral response properties and ocellar inputs of an anatomically identified descending neuron (DNII(2)) in the honeybee optomotor pathway. Using a panoramic stimulus, we show that it responds selectively to optic flow associated with pitch rotations. The neuron is also stimulated with a custom-built light-emitting diode array that presented moving bars that were either all-green (spectrum 500-600 nm, peak 530 nm) or all-short wavelength (spectrum 350-430 nm, peak 380 nm). Although the optomotor response is thought to be dominated by green-sensitive inputs, we show that DNII(2) is equally responsive to, and direction selective to, both green- and short-wavelength stimuli. The color of the background image also influences the spontaneous spiking behavior of the cell: a green background produces significantly higher spontaneous spiking rates. Stimulating the ocelli produces strong modulatory effects on DNII(2), significantly increasing the amplitude of its responses in the preferred motion direction and decreasing the response latency by adding a directional, short-latency response component. Our results suggest that the spectral sensitivity of the optomotor response in honeybees may be more complicated than previously thought and that ocelli play a significant role in shaping the timing of motion signals.

Visual response properties of neck motor neurons in the honeybee.

Recent behavioural studies have demonstrated that honeybees use visual feedback to stabilize their gaze. However, little is known about the neural circuits that perform the visual motor computations that underlie this ability. We investigated the motor neurons that innervate two neck muscles (m44 and m51), which produce stabilizing yaw movements of the head. Intracellular recordings were made from five (out of eight) identified neuron types in the first cervical nerve (IK1) of honeybees. Two motor neurons that innervate muscle 51 were found to be direction-selective, with a preference for horizontal image motion from the contralateral to the ipsilateral side of the head. Three neurons that innervate muscle 44 were tuned to detect motion in the opposite direction (from ipsilateral to contralateral). These cells were binocularly sensitive and responded optimally to frontal stimulation. By combining the directional tuning of the motor neurons in an opponent manner, the neck motor system would be able to mediate reflexive optomotor head turns in the direction of image motion, thus stabilising the retinal image. When the dorsal ocelli were covered, the spontaneous activity of neck motor neurons increased and visual responses were modified, suggesting an ocellar input in addition to that from the compound eyes.

Differential changes in perceived contrast following contrast adaptation in humans.

Perceived contrast is reduced after prolonged exposure to a textured pattern (contrast adaptation). The size of this effect is dependent on the relationship between the adapting contrast and the test contrast. It is generally accepted that the greatest reductions occur when the adapting contrast is much higher than the test contrast. Here this relationship was examined for a wide range of spatial frequencies. The results show that the effect of the adapt/test ratio on perceived contrast following contrast adaptation is highly spatial frequency dependent. At high spatial frequencies >1cpd perceived contrast was reduced for all adapting contrasts, which is consistent with other studies. However, at low spatial frequencies (<1cpd) the perceived contrast was actually above veridical perception when the adapting contrast was lower than the test contrast. This finding has not been previously reported and has important implications for models of contrast perception.

Dynamic contrast change produces rapid gain control in visual cortex.

During normal vision, objects moving in the environment, our own body movements and our eye movements ensure that the receptive fields of visual neurons are being presented with continually changing contrasts. Thus, the visual input during normal behaviour differs from the type of stimuli traditionally used to study contrast coding, which are presented in a step-like manner with abrupt changes in contrast followed by prolonged exposure to a constant stimulus. The abrupt changes in contrast typically elicit brief periods of intense firing with low variability called onset transients. Onset transients provide the visual system with a powerful and reliable cue that the visual input has changed. In this paper we investigate visual processing in the primary visual cortex of cats in response to stimuli that change contrast dynamically. We show that 1-4 s presentations of dynamic increases and decreases in contrast can generate stronger contrast gain control than several minutes exposure to a stimulus of constant contrast. Thus, transient mechanisms of contrast coding are not only less variable than sustained responses but are also more rapid and flexible. Finally, we propose a quantitative model of contrast coding which accounts for changes in spike rate over time in response to dynamically changing image contrast.

Influence of adapting speed on speed and contrast coding in the primary visual cortex of the cat.

Adaptation is a ubiquitous property of the visual system. Adaptation often improves the ability to discriminate between stimuli and increases the operating range of the system, but is also associated with a reduced ability to veridically code stimulus attributes. Adaptation to luminance levels, contrast, orientation, direction and spatial frequency has been studied extensively, but knowledge about adaptation to image speed is less well understood. Here we examined how the speed tuning of neurons in cat primary visual cortex was altered after adaptation to speeds that were slow, optimal, or fast relative to each neuron's speed response function. We found that the preferred speed (defined as the speed eliciting the peak firing rate) of the neurons following adaptation was dependent on the speed at which they were adapted. At the population level cells showed decreases in preferred speed following adaptation to speeds at or above the non-adapted speed, but the preferred speed did not change following adaptation to speeds lower than the non-adapted peak. Almost all cells showed response gain control (reductions in absolute firing capacity) following speed adaptation. We also investigated the speed dependence of contrast adaptation and found that most cells showed contrast gain control (rightward shifts of their contrast response functions) and response gain control following adaptation at any speed. We conclude that contrast adaptation may produce the response gain control associated with speed adaptation, but shifts in preferred speed require an additional level of processing beyond contrast adaptation. A simple model is presented that is able to capture most of the findings.

Complex cells increase their phase sensitivity at low contrasts and following adaptation.

One of the best-known dichotomies in neuroscience is the division of neurons in the mammalian primary visual cortex into simple and complex cells. Simple cells have receptive fields with separate on and off subregions and give phase-sensitive responses to moving gratings, whereas complex cells have uniform receptive fields and are phase invariant. The phase sensitivity of a cell is calculated as the ratio of the first Fourier coefficient (F1) to the mean time-average (Fo) of the response to moving sinusoidal gratings at 100% contrast. Cells are then classified as simple (F1/Fo >1) or complex (F1/Fo <1). We manipulated cell responses by changing the stimulus contrast or through adaptation. The F(1)/F(0) ratios of cells defined as complex at 100% contrast increased at low contrasts and following adaptation. Conversely, the F1/Fo ratios remained constant for cells defined as simple at 100% contrast. The latter cell type was primarily located in thalamorecipient layers 4 and 6. Many cells initially classified as complex exhibit F1/Fo >1 at low contrasts and after adaptation (particularly in layer 4). The results are consistent with the spike-threshold hypothesis, which suggests that the division of cells into two types arises from the nonlinear interaction of spike threshold with membrane potential responses.

Enhanced motion sensitivity follows saccadic suppression in the superior temporal sulcus of the macaque cortex.

The responses of neurons in the middle temporal and medial superior temporal areas of macaque cortex are suppressed during saccades compared with saccade-like stimulus movements. We utilized the short-latency ocular following paradigm to show that this saccadic suppression is followed by postsaccadic enhancement of motion responses. The level of enhancement decays with a time constant of 100 ms from saccade end. The speed of ocular following is also enhanced after saccades and decays over a similar time course, suggesting a link between the neural and behavioral effects. There is some evidence that maximum postsaccadic enhancement occurs when cells are stimulated at their optimum speeds. Latencies of motion responses are saccade dependent: 37 ms for saccade-generated motion, 45 ms for motion in the half-second after saccades, and 70 ms with no prior saccades. The finding that saccades alter response latencies may partially explain perceptual time compression during saccades and time dilation after saccades.

Contrast gain control is drift-rate dependent: an informational analysis.

Neurons in the visual cortex code relative changes in illumination (contrast) and adapt their sensitivities to the visual scene by centering the steepest regions of their sigmoidal contrast response functions (CRFs: spike rate as a function of contrast) on the prevailing contrast. The influence of this contrast gain control has not been reported at nonoptimal drift rates. We calculated the Fisher information contained in the CRFs of halothane-anesthetized cats. Fisher information gives a measure of the accuracy of contrast representations based on the ratio of the square of the steepness of the CRF and the spike-rate dependency of the spiking variance. Variance increases with spike rate, so Fisher information is maximal where the CRF is steep and spike rates are low. Here, we show that the contrast at which the maximal Fisher information (C(MFI)) occurs for each adapting drift rate is at a fixed level above the adapting contrast. For adapting contrasts of 0 to 0.32 the relationship between C(MFI) and adapting contrast is well described by a straight line with a slope close to 1. The intercept of this line on the C(MFI)-axis is drift-rate dependent, although the slope is not. At high drift rates relative to each cell's peak the C(MFI) offset is higher than that for low drift rates. The results show that the contrast coding strategy in visual cortex maximizes accuracy for contrasts above the prevailing contrast in the environment for all drift rates. We argue that tuning the system for accuracy at contrasts above the prevailing value is optimal for viewing natural scenes.

Neurons in V1, V2, and PMLS of cat cortex are speed tuned but not acceleration tuned: the influence of motion adaptation.

We studied neurons in areas V1, V2, and posteromedial lateral suprasylvian area (PMLS) of anesthetized cats, assessing their speed tuning using steps to constant speeds and acceleration and deceleration tuning using speed ramps. The results show that the speed tuning of neurons in all three cortical areas is highly dependent on prior motion history, with early responses during speed steps tuned to higher speeds than later responses. The responses to speed ramps are profoundly influenced by speed-dependent response latencies and ongoing changes in neuronal speed tuning due to adaptation. Acceleration evokes larger transient and sustained responses than subsequent deceleration of the same rate with this disparity increasing with ramp rate. Consequently, there was little correlation between preferred speeds measured using speed steps, acceleration or deceleration. From 146 recorded cells, the proportion of cells that were clearly speed tuned ranged from 69 to 100% across the three brain areas. However, only 13 cells showed good skewed Gaussian fits and systematic variation in their responses to a range of accelerations. Although suggestive of acceleration coding, this apparent tuning was attributable to a cell's speed tuning and the different stimulus durations at each acceleration rate. Thus while the majority of cells showed speed tuning, none unequivocally showed acceleration tuning. The results are largely consistent with an existing model that predicts responses to accelerating stimuli developed for macaque MT, which showed that the responses to acceleration can be decoded if adaptation is taken into account. However, the present results suggest future models should include stimulus-specific adaptation and speed-dependent response latencies.

Relationship between contrast adaptation and orientation tuning in V1 and V2 of cat visual cortex.

Previous studies investigating the response properties of neurons in the primary visual cortex of cats and primates have shown that prolonged exposure to optimally oriented, high-contrast gratings leads to a reduction in responsiveness to subsequently presented test stimuli. We recorded from 119 neurons in cat V1 and V2 and found that in a high proportion of cells contrast adaptation also occurs for gratings oriented orthogonal to a neuron's preferred orientation, even though this stimulus did not elicit significant increases in spiking activity. Approximately 20% of neurons adapted equally to all orientations tested and a further 46% showed at least some adaptation to orthogonally oriented gratings, whereas 20% of neurons did not adapt to orthogonal gratings. The magnitude of contrast adaptation was positively correlated with adapting contrast, but was not related to the spiking activity of the cells. Highly direction selective neurons produced stronger adaptation to orthogonally oriented gratings than other neurons. Orientation-related adaptation was correlated with the rate of change of orientation tuning in consecutive cells along electrode penetrations that traveled parallel to the cortical layers. Nonoriented adaptation was most common in areas where orientation preference changed rapidly, whereas orientation-selective adaptation was most common in areas where orientation preference changed slowly. A minority of neurons did not show contrast adaptation (14%). No major differences were found between units in different cortical layers, V1 and V2, or between complex and simple cells. The relevance of these findings to the current understanding of adaptation within the context of orientation column architecture is discussed.

Comparing acceleration and speed tuning in macaque MT: physiology and modeling.

Studies of individual neurons in area MT have traditionally investigated their sensitivity to constant speeds. We investigated acceleration sensitivity in MT neurons by comparing their responses to constant steps and linear ramps in stimulus speed. Speed ramps constituted constant accelerations and decelerations between 0 and 240 degrees /s. Our results suggest that MT neurons do not have explicit acceleration sensitivity, although speed changes affected their responses in three main ways. First, accelerations typically evoked higher responses than the corresponding deceleration rate at all rates tested. We show that this can be explained by adaptation mechanisms rather than differential processing of positive and negative speed gradients. Second, we inferred a cell's preferred speed from the responses to speed ramps by finding the stimulus speed at the latency-adjusted time when response amplitude peaked. In most cells, the preferred speeds inferred from deceleration were higher than those for accelerations of the same rate or from steps in stimulus speed. Third, neuron responses to speed ramps were not well predicted by the transient or sustained responses to steps in stimulus speed. Based on these findings, we developed a model incorporating adaptation and a neuron's speed tuning that predicted the higher inferred speeds and lower spike rates for deceleration responses compared with acceleration responses. This model did not predict acceleration-specific responses, in accordance with the lack of acceleration sensitivity in the neurons. The outputs of this single-cell model were passed to a population-vector-based model used to estimate stimulus speed and acceleration. We show that such a model can accurately estimate relative speed and acceleration using information from the population of neurons in area MT.

Rapid processing of retinal slip during saccades in macaque area MT.

The primate middle temporal area (MT) is involved in the analysis and perception of visual motion, which is generated actively by eye and body movements and passively when objects move. We studied the responses of single cells in area MT of awake macaques, comparing the direction tuning and latencies of responses evoked by wide-field texture motion during fixation (passive viewing) and during rewarded, target-directed saccades and non-rewarded, spontaneous saccades over the same stationary texture (active viewing). We found that MT neurons have similar motion sensitivity and direction-selectivity for retinal slip associated with active and passive motion. No cells showed reversals in direction tuning between the active and passive viewing conditions. However, mean latencies were significantly different for saccade-evoked responses (30 ms) and stimulus-evoked responses (67 ms). Our results demonstrate that neurons in area MT retain their direction-selectivity and display reduced processing times during saccades. This rapid, accurate processing of peri-saccadic motion may facilitate post-saccadic ocular following reflexes or corrective saccades.

Contrast and temporal frequency-related adaptation in the pretectal nucleus of the optic tract.

In mammals, many cells in the retino-geniculate-cortical pathway adapt during stimulation with high contrast gratings. In the visual cortex, adaptation to high contrast images reduces sensitivity at low contrasts while only moderately affecting sensitivity at high contrasts, thus generating rightward shifts in the contrast response functions (contrast gain control). Similarly, motion adaptation at particular temporal frequencies (TFs) alters the temporal tuning properties of cortical cells. For the first time in any species, this paper investigates the influence of motion adaptation on both the contrast and TF responses of neurons in the retino-pretectal pathway by recording from direction-selective neurons in the nucleus of the optic tract (NOT) of the marsupial wallaby, Macropus eugenii. This species is of interest because its NOT receives almost all input directly from the retina, with virtually none from the visual cortex (unlike cats and primates). All NOT cells show changes in their contrast response functions after adaptation, many revealing contrast gain control. Contrast adaptation is direction-dependent, preferred directions producing the largest changes. The lack of cortical input suggests that contrast adaptation is generated independently from the cortex in the NOT or retina. Motion adaptation also produces direction-selective effects on the TF tuning of NOT neurons by shifting the location of the optimum TF. Cells that show strong adaptation to contrast also tend to show large changes in TF tuning, suggesting similar intracellular mechanisms. The data are discussed in terms of the generality of contrast adaptation across mammalian species and across unconnected brain regions within the same species.