VIP Neurons Research Articles

Vitamins C and E (ascorbate/α-tocopherol) provide synergistic neuroprotection in the jejunum in experimental diabetes

The present study evaluated the synergistic effects of the association of ascorbic acid and α-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons (p<0.05). The association of ascorbic acid and α-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons.

Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field.

Both visual and vestibular sensory cues are important for perceiving one's direction of heading during self-motion. Previous studies have identified multisensory, heading-selective neurons in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP). Both MSTd and VIP have strong recurrent connections with the pursuit area of the frontal eye field (FEFsem), but whether FEFsem neurons may contribute to multisensory heading perception remain unknown. We characterized the tuning of macaque FEFsem neurons to visual, vestibular, and multisensory heading stimuli. About two-thirds of FEFsem neurons exhibited significant heading selectivity based on either vestibular or visual stimulation. These multisensory neurons shared many properties, including distributions of tuning strength and heading preferences, with MSTd and VIP neurons. Fisher information analysis also revealed that the average FEFsem neuron was almost as sensitive as MSTd or VIP cells. Visual and vestibular heading preferences in FEFsem tended to be either matched (congruent cells) or discrepant (opposite cells), such that combined stimulation strengthened heading selectivity for congruent cells but weakened heading selectivity for opposite cells. These findings demonstrate that, in addition to oculomotor functions, FEFsem neurons also exhibit properties that may allow them to contribute to a cortical network that processes multisensory heading cues.

Differential Impact of Behavioral Relevance on Quantity Coding in Primate Frontal and Parietal Neurons

Prefrontal cortex (PFC) and posterior parietal cortex are key brain areas for magnitude representations. Whether active discrimination of numerosity changes neuronal representations is still not known. We simultaneously recorded from the same recording sites in the PFC and ventral intraparietal area (VIP) before and after monkeys learned to actively discriminate the number of items in a set. Only PFC neurons, and not VIP neurons, exhibited heightened representation of number after numerosity training. Increased responsiveness of PFC was evidenced by enhanced differentiation of numerosity by the population of neurons, as well as increased numerosity encoding by individual selective neurons. None of these effects were observed in the VIP, in which neurons responded invariably to numerosity irrespective of behavioral relevance. This suggests elevated PFC participation during numerical task demands and executive control, whereas VIP encodes quantity as a perceptual category regardless of behavioral relevance.

617 Efficient Gene Delivery to the Enteric Nervous System by IV Delivery of AAV Vectors

Gene therapy may be useful to treat and study the enteric nervous system (ENS). In this study, we characterized transduction efficiency and distribution in the myenteric and submucosal plexuses following intravenous (IV) injection of adeno-associated viral vectors (AAV) expressing GFP in mice. Neonate (P1) mice were injected with AAV9-CB-GFP (3 x 1011 vg) in the temporal vein and juvenile mice (P21) received tail vein injections (2 x 1012 vg). Mice were euthanized at 60-90 days of age, and the myenteric plexus was examined. GFP positive myenteric neurons were found along the entire GI tract in injected mice. Segmental examinations of myenteric neurons in the colon showed no oral-aboral bias. Neuronal transduction ranged from 21-57% depending on the region. GFP co-localized with interneurons, excitatory and sensory myenteric neurons. In contrast, GFP expression in VIP, nNOS and glial cells was absent. However, IV injection of AAV9 with a glial promoter (GFAP) drove GFP expression exclusively in glia. Neonate IV injections with AAV1, 5, and 6 containing the CB-GFP expression cassette produced little to no transgene expression in the myenteric plexus. However, AAV8-CB-GFP showed significantly higher neuronal transduction compared to AAV9 injected mice. AAV8-CB-GFP expressed in all ENS cell types examined including VIP and nNOS neurons and intraganglionic S100 glia. Characterization of AAV-CB-GFP transduction in submucosal neurons is ongoing. These data demonstrate that the ENS is efficiently targeted by AAV8 and AAV9 following IV delivery. Further, transgene expression can be customized with changes in the viral capsid and expression cassette.

618 Effect of Anesthesia in Colon Motility: Prospective Study of Children With Intractable Constipation Undergoing Colon Manometry

Gene therapy may be useful to treat and study the enteric nervous system (ENS). In this study, we characterized transduction efficiency and distribution in the myenteric and submucosal plexuses following intravenous (IV) injection of adeno-associated viral vectors (AAV) expressing GFP in mice. Neonate (P1) mice were injected with AAV9-CB-GFP (3 x 1011 vg) in the temporal vein and juvenile mice (P21) received tail vein injections (2 x 1012 vg). Mice were euthanized at 60-90 days of age, and the myenteric plexus was examined. GFP positive myenteric neurons were found along the entire GI tract in injected mice. Segmental examinations of myenteric neurons in the colon showed no oral-aboral bias. Neuronal transduction ranged from 21-57% depending on the region. GFP co-localized with interneurons, excitatory and sensory myenteric neurons. In contrast, GFP expression in VIP, nNOS and glial cells was absent. However, IV injection of AAV9 with a glial promoter (GFAP) drove GFP expression exclusively in glia. Neonate IV injections with AAV1, 5, and 6 containing the CB-GFP expression cassette produced little to no transgene expression in the myenteric plexus. However, AAV8-CB-GFP showed significantly higher neuronal transduction compared to AAV9 injected mice. AAV8-CB-GFP expressed in all ENS cell types examined including VIP and nNOS neurons and intraganglionic S100 glia. Characterization of AAV-CB-GFP transduction in submucosal neurons is ongoing. These data demonstrate that the ENS is efficiently targeted by AAV8 and AAV9 following IV delivery. Further, transgene expression can be customized with changes in the viral capsid and expression cassette.

Visual selectivity for heading in the macaque ventral intraparietal area.

The patterns of optic flow seen during self-motion can be used to determine the direction of one's own heading. Tracking eye movements which typically occur during everyday life alter this task since they add further retinal image motion and (predictably) distort the retinal flow pattern. Humans employ both visual and nonvisual (extraretinal) information to solve a heading task in such case. Likewise, it has been shown that neurons in the monkey medial superior temporal area (area MST) use both signals during the processing of self-motion information. In this article we report that neurons in the macaque ventral intraparietal area (area VIP) use visual information derived from the distorted flow patterns to encode heading during (simulated) eye movements. We recorded responses of VIP neurons to simple radial flow fields and to distorted flow fields that simulated self-motion plus eye movements. In 59% of the cases, cell responses compensated for the distortion and kept the same heading selectivity irrespective of different simulated eye movements. In addition, response modulations during real compared with simulated eye movements were smaller, being consistent with reafferent signaling involved in the processing of the visual consequences of eye movements in area VIP. We conclude that the motion selectivities found in area VIP, like those in area MST, provide a way to successfully analyze and use flow fields during self-motion and simultaneous tracking movements.

Eye-centered visual receptive fields in the ventral intraparietal area.

The ventral intraparietal area (VIP) processes multisensory visual, vestibular, tactile, and auditory signals in diverse reference frames. We recently reported that visual heading signals in VIP are represented in an approximately eye-centered reference frame when measured using large-field optic flow stimuli. No VIP neuron was found to have head-centered visual heading tuning, and only a small proportion of cells had reference frames that were intermediate between eye- and head-centered. In contrast, previous studies using moving bar stimuli have reported that visual receptive fields (RFs) in VIP are head-centered for a substantial proportion of neurons. To examine whether these differences in previous findings might be due to the neuronal property examined (heading tuning vs. RF measurements) or the type of visual stimulus used (full-field optic flow vs. a single moving bar), we have quantitatively mapped visual RFs of VIP neurons using a large-field, multipatch, random-dot motion stimulus. By varying eye position relative to the head, we tested whether visual RFs in VIP are represented in head- or eye-centered reference frames. We found that the vast majority of VIP neurons have eye-centered RFs with only a single neuron classified as head-centered and a small minority classified as intermediate between eye- and head-centered. Our findings suggest that the spatial reference frames of visual responses in VIP may depend on the visual stimulation conditions used to measure RFs and might also be influenced by how attention is allocated during stimulus presentation.

Neuro-Anatomical Evidence Indicating Indirect Modulation of Macrophages by Vagal Efferents in the Intestine but Not in the Spleen

BackgroundElectrical stimulation of the vagus nerve suppresses intestinal inflammation and normalizes gut motility in a mouse model of postoperative ileus. The exact anatomical interaction between the vagus nerve and the intestinal immune system remains however a matter of debate. In the present study, we provide additional evidence on the direct and indirect vagal innervation of the spleen and analyzed the anatomical evidence for neuroimmune modulation of macrophages by vagal preganglionic and enteric postganglionic nerve fibers within the intestine.MethodsDextran conjugates were used to label vagal preganglionic (motor) fibers projecting to the small intestine and spleen. Moreover, identification of the neurochemical phenotype of the vagal efferent fibers and enteric neurons was performed by immunofluorescent labeling. F4/80 antibody was used to label resident macrophages.ResultsOur anterograde tracing experiments did not reveal dextran-labeled vagal fibers or terminals in the mesenteric ganglion or spleen. Vagal efferent fibers were confined within the myenteric plexus region of the small intestine and mainly endings around nNOS, VIP and ChAT positive enteric neurons. nNOS, VIP and ChAT positive fibers were found in close proximity of intestinal resident macrophages carrying α7 nicotinic receptors. Of note, VIP receptors were found on resident macrophages located in close proximity of VIP positive nerve fibers.ConclusionIn the present study, we show that the vagus nerve does not directly interact with resident macrophages in the gut or spleen. Instead, the vagus nerve preferentially interacts with nNOS, VIP and ChAT enteric neurons located within the gut muscularis with nerve endings in close proximity of the resident macrophages.

Inhibitory Neurons: Vip Cells Hit the Brake on Inhibition

Recent studies on vasoactive intestinal peptide-expressing inhibitory neurons in the barrel and auditory cortices of the mouse brain have shown that they form a disinhibitory circuitry that affects the excitability of pyramidal neurons.

Eye-Centered Representation of Optic Flow Tuning in the Ventral Intraparietal Area

Reference frames are important for understanding sensory processing in the cortex. Previous work showed that vestibular heading signals in the ventral intraparietal area (VIP) are represented in body-centered coordinates. In contrast, vestibular heading tuning in the medial superior temporal area (MSTd) is approximately head centered. We considered the hypothesis that visual heading signals (from optic flow) in VIP might also be transformed into a body-centered representation, unlike visual heading tuning in MSTd, which is approximately eye centered. We distinguished among eye-centered, head-centered, and body-centered spatial reference frames by systematically varying both eye and head positions while rhesus monkeys viewed optic flow stimuli depicting various headings. We found that heading tuning of VIP neurons based on optic flow generally shifted with eye position, indicating an eye-centered spatial reference frame. This is similar to the representation of visual heading signals in MSTd, but contrasts sharply with the body-centered representation of vestibular heading signals in VIP. These findings demonstrate a clear dissociation between the spatial reference frames of visual and vestibular signals in VIP, and emphasize that frames of reference for neurons in parietal cortex can depend on the type of sensory stimulation.

Functional specializations of the ventral intraparietal area for multisensory heading discrimination.

The ventral intraparietal area (VIP) of the macaque brain is a multimodal cortical region with directionally selective responses to visual and vestibular stimuli. To explore how these signals contribute to self-motion perception, neural activity in VIP was monitored while macaques performed a fine heading discrimination task based on vestibular, visual, or multisensory cues. For neurons with congruent visual and vestibular heading tuning, discrimination thresholds improved during multisensory stimulation, suggesting that VIP (like the medial superior temporal area; MSTd) may contribute to the improved perceptual discrimination seen during cue combination. Unlike MSTd, however, few VIP neurons showed opposite visual/vestibular tuning over the range of headings relevant to behavior, and those few cells showed reduced sensitivity under cue combination. Our data suggest that the heading tuning of some VIP neurons may be locally remodeled to increase the proportion of cells with congruent tuning over the behaviorally relevant stimulus range. VIP neurons also showed much stronger trial-by-trial correlations with perceptual decisions (choice probabilities; CPs) than MSTd neurons. While this may suggest that VIP neurons are more strongly linked to heading perception, we also find that correlated noise is much stronger among pairs of VIP neurons, with noise correlations averaging 0.14 in VIP as compared with 0.04 in MSTd. Thus, the large CPs in VIP could be a consequence of strong interneuronal correlations. Together, our findings suggest that VIP neurons show specializations that may make them well equipped to play a role in multisensory integration for heading perception.

Encoding of movement in near extrapersonal space in primate area VIP

Many neurons in the macaque ventral intraparietal area (VIP) are multimodal, i.e., they respond not only to visual but also to tactile, auditory and vestibular stimulation. Anatomical studies have shown distinct projections between area VIP and a region of premotor cortex controlling head movements. A specific function of area VIP could be to guide movements in order to head for and/or to avoid objects in near extrapersonal space. This behavioral role would require a consistent representation of visual motion within 3-D space and enhanced activity for nearby motion signals. Accordingly, in our present study we investigated whether neurons in area VIP are sensitive to moving visual stimuli containing depth signals from horizontal disparity. We recorded single unit activity from area VIP of two awake behaving monkeys (Macaca mulatta) fixating a central target on a projection screen. Sensitivity of neurons to horizontal disparity was assessed by presenting large field moving images (random dot fields) stereoscopically to the two eyes by means of LCD shutter goggles synchronized with the stimulus computer. During an individual trial, stimuli had one of seven different disparity values ranging from 3° uncrossed- (far) to 3° crossed- (near) disparity in 1° steps. Stimuli moved at constant speed in all simulated depth planes. Different disparity values were presented across trials in pseudo-randomized order. Sixty-one percent of the motion sensitive cells had a statistically significant selectivity for the horizontal disparity of the stimulus (p < 0.05, distribution free ANOVA). Seventy-five percent of them preferred crossed-disparity values, i.e., moving stimuli in near space, with the highest mean activity for the nearest stimulus. At the population level, preferred direction of visual stimulus motion was not affected by horizontal disparity. Thus, our findings are in agreement with the behavioral role of area VIP in the representation of movement in near extrapersonal space.

Regenerative process evaluation of neuronal subclasses in chagasic patients with megacolon

Chagas' disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system (ENS) components leads to megacolon development. Previous data presented that the regeneration tax in the ENS neurons is augmented in chagasic patients. Although, there are several neuronal types with different functions in the intestine a detailed study about the regeneration of every neuronal type was never performed before. Therefore, the aim of this study was to evaluate the regeneration tax of every neuronal cell type in the ENS from chagasic patients with megacolon and non-infected individuals. A neuronal regeneration marker (GAP-43) was used in combination with a pan-neuronal marker (Peripherin) and several neuropeptides markers (cChat, Substance P, NPY, VIP and NOS), and it was considered as positive just with the combination of these markers. Our results demonstrated that the regeneration levels of cChat, Substance P, and NPY were similar in chagasic patients and non-infected individuals. However, levels of VIP and NOS neuropeptides were increased in chagasic patients when compared with non-infected individuals. We believe that the augment in the regeneration occur due to an increased destruction of selective neuronal types. These results corroborates with previous studies that pointed out to selective destruction of VIP and NOS neurons in chagasic patients.

Parkinson’s disease is not associated with gastrointestinal myenteric ganglion neuron loss

Gastrointestinal dysfunction is a prominent non-motor feature of Parkinson's disease (PD) that contributes directly to the morbidity of patients, complicates management of motor symptoms, and may herald incipient PD in patients without motor disability. Although PD has traditionally been considered a disease of dopaminergic neurons in the substantia nigra, analyses of gastrointestinal samples from PD patients have consistently revealed pathology in the enteric nervous system. The relationship of PD pathology to GI dysmotility is poorly understood, and this lack of understanding has led to limited success in developing treatments for PD-related GI symptoms. We have quantitatively compared myenteric neuron density and relative abundance of NO, VIP, and catecholamine neurons between patients with PD and control individuals along the length of the GI tract. In addition, we have examined the frequency of GI α-synuclein neuritic pathology and its co-localization with the same neuronal markers. We have included a comparison with a small population of patients with incidental Lewy bodies found at autopsy. These data indicate that there is no neuronal loss in the myenteric plexus in PD. Lewy body pathology parallels parasympathetic autonomic input from the dorsal motor nucleus of the vagus, not the distribution of extrinsic sympathetic input or intrinsic enteric neurons, and is only rarely co-localized with tyrosine hydroxylase. These data provide a critical background to which further analyses of the effect of PD on the GI tract may be compared and suggest that neuropathology in myenteric neurons is unlikely to be a causative factor in PD-related GI dysmotility.

Face-infringement space: the frame of reference of the ventral intraparietal area

Experimental studies have shown that responses of ventral intraparietal area (VIP) neurons specialize in head movements and the environment near the head. VIP neurons respond to visual, auditory, and tactile stimuli, smooth pursuit eye movements, and passive and active movements of the head. This study demonstrates mathematical structure on a higher organizational level created within VIP by the integration of a complete set of variables covering face-infringement. Rather than positing dynamics in an a priori defined coordinate system such as those of physical space, we assemble neuronal receptive fields to find out what space of variables VIP neurons together cover. Section 1 presents a view of neurons as multidimensional mathematical objects. Each VIP neuron occupies or is responsive to a region in a sensorimotor phase space, thus unifying variables relevant to the disparate sensory modalities and movements. Convergence on one neuron joins variables functionally, as space and time are joined in relativistic physics to form a unified spacetime. The space of position and motion together forms a neuronal phase space, bridging neurophysiology and the physics of face-infringement. After a brief review of the experimental literature, the neuronal phase space natural to VIP is sequentially characterized, based on experimental data. Responses of neurons indicate variables that may serve as axes of neural reference frames, and neuronal responses have been so used in this study. The space of sensory and movement variables covered by VIP receptive fields joins visual and auditory space to body-bound sensory modalities: somatosensation and the inertial senses. This joining of allocentric and egocentric modalities is in keeping with the known relationship of the parietal lobe to the sense of self in space and to hemineglect, in both humans and monkeys. Following this inductive step, variables are formalized in terms of the mathematics of graph theory to deduce which combinations are complete as a multidimensional neural structure that provides the organism with a complete set of options regarding objects impacting the face, such as acceptance, pursuit, and avoidance. We consider four basic variable types: position and motion of the face and of an external object. Formalizing the four types of variables allows us to generalize to any sensory system and to determine the necessary and sufficient conditions for a neural center (for example, a cortical region) to provide a face-infringement space. We demonstrate that VIP includes at least one such face-infringement space.

Inferotemporal Cortex Subserves Three-Dimensional Structure Categorization

We perceive real-world objects as three-dimensional (3D), yet it is unknown which brain area underlies our ability to perceive objects in this way. The macaque inferotemporal (IT) cortex contains neurons that respond selectively to 3D structures defined by binocular disparity. To examine the causal role of IT in the categorization of 3D structures, we electrically stimulated clusters of IT neurons with a similar 3D-structure preference while monkeys performed a 3D-structure categorization task. Microstimulation of 3D-structure-selective IT clusters caused monkeys to choose the preferred structure of the 3D-structure-selective neurons considerably more often. Microstimulation in IT also accelerated the monkeys' choice for the preferred structure, while delaying choices corresponding to the nonpreferred structure of a given site. These findings reveal that 3D-structure-selective neurons in IT contribute to the categorization of 3D objects.

Representation of Vestibular and Visual Cues to Self-Motion in Ventral Intraparietal Cortex

Convergence of vestibular and visual motion information is important for self-motion perception. One cortical area that combines vestibular and optic flow signals is the ventral intraparietal area (VIP). We characterized unisensory and multisensory responses of macaque VIP neurons to translations and rotations in three dimensions. Approximately one-half of VIP cells show significant directional selectivity in response to optic flow, one-half show tuning to vestibular stimuli, and one-third show multisensory responses. Visual and vestibular direction preferences of multisensory VIP neurons could be congruent or opposite. When visual and vestibular stimuli were combined, VIP responses could be dominated by either input, unlike the medial superior temporal area (MSTd) where optic flow tuning typically dominates or the visual posterior sylvian area (VPS) where vestibular tuning dominates. Optic flow selectivity in VIP was weaker than in MSTd but stronger than in VPS. In contrast, vestibular tuning for translation was strongest in VPS, intermediate in VIP, and weakest in MSTd. To characterize response dynamics, direction-time data were fit with a spatiotemporal model in which temporal responses were modeled as weighted sums of velocity, acceleration, and position components. Vestibular responses in VIP reflected balanced contributions of velocity and acceleration, whereas visual responses were dominated by velocity. Timing of vestibular responses in VIP was significantly faster than in MSTd, whereas timing of optic flow responses did not differ significantly among areas. These findings suggest that VIP may be proximal to MSTd in terms of vestibular processing but hierarchically similar to MSTd in terms of optic flow processing.

Parietal Area VIP Causally Influences Heading Perception during Pursuit Eye Movements

The ventral intraparietal area (VIP) of the macaque monkey brain is a multimodal area with visual, vestibular, somatosensory, and eye movement-related responses. The visual responses are strongly directional, and VIP neurons respond well to complex optic flow patterns similar to those found during self-motion. To test the hypothesis that visual responses in VIP directly contribute to the perception of self-motion direction, we used electrical microstimulation to perturb activity in VIP while animals performed a two-alternative heading discrimination task. Microstimulation systematically biased monkeys' choices in a direction consistent with neuronal preferences at the stimulation site, and these effects were larger while the animal was making smooth pursuit eye movements. From these results, we conclude that VIP is causally involved in the perception of self-motion from visual cues and that this involvement is gated by ongoing motor behavior.

Cholecystokinin (CCK)‐expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK‐deficient mice

The suprachiasmatic nucleus (SCN) is the principal pacemaker driving circadian rhythms of physiology and behaviour. Neurons within the SCN express both classical and neuropeptide transmitters which regulate clock functions. Cholecyctokinin (CCK) is a potent neurotransmitter expressed in neurons of the mammalian SCN, but its role in circadian timing is not known. In the present study, CCK was demonstrated in a distinct population of neurons located in the shell region of the SCN and in a few cells in the core region. The CCK neurons did not express vasopressin or vasoactive intestinal peptide. However, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of cFOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar τ, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting of the clock or in regulating core clock function. The expression of CCK in a subpopulation of neurons, which do not belonging to either the VIP or AVP cells but which have synaptic contacts to both cell types and reverse innervation of CCK neurons from VIP neurons, suggests that the CCK neurons may act in non-photic regulation within the clock and/or, via CCK projections, mediate clock information to hypothalamic nuclei.

Extrastriate Area MST and Parietal Area VIP Similarly Represent Forward Headings

Many studies have documented the involvement of medial superior temporal extrastriate area (MST) in the perception of heading based on optic flow information. Furthermore, both heading perception and the responses of MST neurons are relatively stable in the presence of eye movements that distort the retinal flow information on which perception is based. Area VIP in the posterior parietal cortex also contains a robust representation of optic flow cues for heading. However, the studies in the two areas were frequently conducted using different stimuli, making quantitative comparison difficult. To remedy this, we studied MST using a family of random dot heading stimuli that we have previously used in the study of VIP. These stimuli simulate observer translation through a three-dimensional cloud of points, and a range of forward headings was presented both with and without horizontal smooth pursuit eye movements. We found that MST neurons, like VIP neurons, respond robustly to these stimuli and partially compensate for the presence of pursuit. Quantitative comparison of the responses revealed no substantial difference between the heading responses of MST and VIP neurons or in their degree of pursuit tolerance.