Cortex Of Nonhuman Primates Research Articles

Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Alterations in cannabinoid CB1 receptor (CB1R) are implicated in various psychiatric disorders. CB1R participates in both depolarization induced suppression of inhibition (DSI) and depolarization induced suppression of excitation (DSE), suggesting its involvement in regulating excitatory and inhibitory (E/I) balance. Prior studies examining neuronal cell type specific CB1R distribution have been conducted near exclusively within rodents. Identification of these distribution patterns within the human and non-human primate cortex is essential to increase our insight into its function. Using co-labeling immunohistochemistry and fluorescent microscopy, we examined CB1R protein levels within excitatory and inhibitory boutons of male human and non-human primate prefrontal cortex and auditory cortices, regions involved in the behavioral effects of exogenous cannabinoid exposures. We found that CB1R was present in both bouton populations within all brain regions examined in both species. Significantly higher CB1R levels were found within inhibitory than within excitatory boutons across all regions in both species, although the cell type by brain region interactions differed between the two species. Our results support the importance of conducting more in-depth CB1R examinations to understand how cell type and brain region dependent differences contribute to regional E/I balance regulation, and how aberrations in CB1R distribution may contribute to pathology.

Propofol Anesthesia Alters Cortical Traveling Waves.

Oscillatory dynamics in cortex seem to organize into traveling waves that serve a variety of functions. Recent studies show that propofol, a widely used anesthetic, dramatically alters cortical oscillations by increasing slow-delta oscillatory power and coherence. It is not known how this affects traveling waves. We compared traveling waves across the cortex of non-human primates before, during, and after propofol-induced loss of consciousness (LOC). After LOC, traveling waves in the slow-delta (∼1 Hz) range increased, grew more organized, and traveled in different directions relative to the awake state. Higher frequency (8-30 Hz) traveling waves, by contrast, decreased, lost structure, and switched to directions where the slow-delta waves were less frequent. The results suggest that LOC may be due, in part, to increases in the strength and direction of slow-delta traveling waves that, in turn, alter and disrupt traveling waves in the higher frequencies associated with cognition.

A cerebellar origin of feedforward inhibition to the motor cortex in non-human primates.

Voluntary movements are driven by coordinated activity across a large population of motor cortical neurons. Formation of this activity is controlled by local interactions and long-range inputs. How remote areas of the brain communicate with motor cortical neurons to effectively drive movement remains unclear. We address this question by studying the cerebellar-thalamocortical system. We find that thalamic input to the motor cortex triggers feedforward inhibition by contacting inhibitory cells via highly effective GluR2-lacking AMPA receptors and that, during task performance, the activity of parvalbumin (PV) and pyramidal cells exhibits relations comparable with movement parameters. We also find that the movement-related activity of PV interneurons precedes firing of pyramidal cells. This counterintuitive sequence of events, where inhibitory cells are recruited more strongly and before excitatory cells, may amplify the cortical effect of cerebellar signals in a way that exceeds their sheer synaptic efficacy by suppressing other inputs.

Network structure mediates functional reorganization induced by optogenetic stimulation of non-human primate sensorimotor cortex

SummaryBecause aberrant network-level functional connectivity underlies a variety of neural disorders, the ability to induce targeted functional reorganization would be a profound development toward therapies for neural disorders. Brain stimulation has been shown to induce large-scale network-wide functional connectivity changes (FCC), but the mapping from stimulation to the induced changes is unclear. Here, we develop a model which jointly considers the stimulation protocol and the cortical network structure to accurately predict network-wide FCC in response to optogenetic stimulation of non-human primate primary sensorimotor cortex. We observe that the network structure has a much stronger effect than the stimulation protocol on the resulting FCC. We also observe that the mappings from these input features to the FCC diverge over frequency bands and successive stimulations. Our framework represents a paradigm shift for targeted neural stimulation and can be used to interrogate, improve, and develop stimulation-based interventions for neural disorders.

Latency shortening with enhanced sparseness and responsiveness in V1 during active visual sensing

In natural vision, neuronal responses to visual stimuli occur due to self-initiated eye movements. Here, we compare single-unit activity in the primary visual cortex (V1) of non-human primates to flashed natural scenes (passive vision condition) to when they freely explore the images by self-initiated eye movements (active vision condition). Active vision enhances the number of neurons responding, and the response latencies become shorter and less variable across neurons. The increased responsiveness and shortened latency during active vision were not explained by increased visual contrast. While the neuronal activities in all layers of V1 show enhanced responsiveness and shortened latency, a significant increase in lifetime sparseness during active vision is observed only in the supragranular layer. These findings demonstrate that the neuronal responses become more distinct in active vision than passive vision, interpreted as consequences of top-down predictive mechanisms.

1024-channel electrophysiological recordings in macaque V1 and V4 during resting state

Co-variations in resting state activity are thought to arise from a variety of correlated inputs to neurons, such as bottom-up activity from lower areas, feedback from higher areas, recurrent processing in local circuits, and fluctuations in neuromodulatory systems. Most studies have examined resting state activity throughout the brain using MRI scans, or observed local co-variations in activity by recording from a small number of electrodes. We carried out electrophysiological recordings from over a thousand chronically implanted electrodes in the visual cortex of non-human primates, yielding a resting state dataset with unprecedentedly high channel counts and spatiotemporal resolution. Such signals could be used to observe brain waves across larger regions of cortex, offering a temporally detailed picture of brain activity. In this paper, we provide the dataset, describe the raw and processed data formats and data acquisition methods, and indicate how the data can be used to yield new insights into the ‘background’ activity that influences the processing of visual information in our brain.

Common principles in the lateralization of auditory cortex structure and function for vocal communication in primates and rodents.

This review summarizes recent findings on the lateralization of communicative sound processing in the auditory cortex (AC) of humans, non-human primates and rodents. Functional imaging in humans has demonstrated a left hemispheric preference for some acoustic features of speech, but it is unclear to which degree this is caused by bottom-up acoustic feature selectivity or top-down modulation from language areas. Although non-human primates show a less pronounced functional lateralization in AC, the properties of AC fields and behavioural asymmetries are qualitatively similar. Rodent studies demonstrate microstructural circuits that might underlie bottom-up acoustic feature selectivity in both hemispheres. Functionally, the left AC in the mouse appears to be specifically tuned to communication calls, whereas the right AC may have a more 'generalist' role. Rodents also show anatomical AC lateralization, such as differences in size and connectivity. Several of these functional and anatomical characteristics are also lateralized in human AC. Thus, complex vocal communication processing shares common features among rodents and primates. We argue that a synthesis of results from humans, non-human primates and rodents is necessary to identify the neural circuitry of vocal communication processing. However, data from different species and methods are often difficult to compare. Recent advances may enable better integration of methods across species. Efforts to standardize data formats and analysis tools would benefit comparative research and enable synergies between psychological and biological research in the area of vocal communication processing.

Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations

Βeta oscillatory activity (human: 13–35 Hz; primate: 8–24 Hz) is pervasive within the cortex and basal ganglia. Studies in Parkinson’s disease patients and animal models suggest that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine tone remains unclear. We recorded neural activity in the cortex and basal ganglia of healthy non-human primates while acutely and chronically up- and down-modulating dopamine levels. We assessed changes in beta oscillations in patients with Parkinson’s following acute and chronic changes in dopamine tone. Here we show beta oscillation frequency is strongly coupled with dopamine tone in both monkeys and humans. Power, coherence between single-units and local field potentials (LFP), spike-LFP phase-locking, and phase-amplitude coupling are not systematically regulated by dopamine levels. These results demonstrate that beta frequency is a key property of pathological oscillations in cortical and basal ganglia networks.

26.3 Cell-Type–Specific Type 1 Cannabinoid Receptor Distribution Across the Human and Nonhuman Primate Cortex

Alterations in the type-1 cannabinoid (CB1) receptor are implicated in various mental health disorders. CB1 participates in both depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE), suggesting CB1's involvement in both inhibitory and excitatory circuits. However, previous studies describing the distribution of CB1 in human and nonhuman primate cortex utilized antibodies that preferentially target CB1 at inhibitory boutons. Given CB1’s role in both DSI and DSE, understanding cell type–specific CB1 distribution may increase our insight into its regulation of excitatory-inhibitory balance. Here, we investigate CB1 distribution in both inhibitory and excitatory boutons using quantitative fluorescent microscopy. Coronal sections containing dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) from adult male macaques and humans are labeled with antibodies for CB1 (validated to target both excitatory and inhibitory boutons), the vesicular glutamate transporter 1 (VGLUT1; labeling intracortical excitatory boutons), and the vesicular GABA transporter (VGAT; labeling intracortical inhibitory boutons). Samples are imaged to visualize protein expression patterns within cortical regions and layers (10 imaged sites per layer for each brain region of each subject). Fluorescent intensities of CB1 label within boutons of each type are compared using multifactorial ANOVA. CB1 co-expression with both VGLUT1 and VGAT are visualized in axons and boutons in all brain regions of both nonhuman primate and human samples. CB1 fluorescent intensity is lower in excitatory boutons compared to inhibitory boutons across all areas (p < 0.01) and exhibits distinct patterns within each brain region and cortical layer. Previous studies describing the distribution of CB1 in human and nonhuman primate cortex utilized antibodies preferentially targeting CB1 at inhibitory boutons. Using a CB1 antibody that targets both excitatory and inhibitory boutons, we demonstrate distinct cell type–specific regional and laminar distributions of CB1 in the human and nonhuman primate cortex. This may increase our understanding of how CB1 differentially regulates excitatory-inhibitory balance within these areas, and whether cell type–specific CB1 disturbances contribute to the development of psychopathology.

Design of a Phase 1/2 Open-Label, Dose-Escalation Study of the Safety and Efficacy of Gene Therapy in Adults With Classic Congenital Adrenal Hyperplasia (CAH) Due to 21-hydroxylase Deficiency Through Administration of an Adeno-Associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2 Gene

Abstract The CYP21A2 gene, which encodes the 21-hydroxylase enzyme, plays a critical role in glucocorticoid (GC) and mineralocorticoid synthesis by the adrenal cortex. CYP21A2 pathogenic variants cause 21-hydroxylase deficiency (21OHD), the most common type of CAH, characterized by variable degrees of adrenal insufficiency and androgen excess. Standard treatment of classic 21OHD consists of daily doses of GC and mineralocorticoid. However, suppressive GC doses are often required to reduce androgen excess, and it is often not possible to dose exogenous GC in a manner that provides adequate disease control while avoiding overtreatment. Disease-related and treatment-related comorbidities are common and include life-threatening adrenal crises, impaired growth and development during childhood, adult short stature, virilization in females, subfertility in both sexes, obesity and cardiovascular risk factors, and decreased bone mineral density. Novel treatment approaches are needed to address these challenges and a treatment that restores the ability of the adrenals to produce cortisol and aldosterone in a physiologically-regulated manner would be particularly helpful. Here we present the design and rationale of a clinical trial using BBP-631, an AAV5 gene replacement therapy for adults with classic CAH due to 21-OHD. This treatment approach is based on the demonstration that a single intravenous administration of BBP-631 corrects the enzyme deficiency in the H2-aw18 CYP21-/- CAH mouse model of 21OHD, including response to stress. This correction was robust, dose-dependent and durable. BBP-631 treatment also resulted in robust and durable expression of the human CYP21A2 transgene in the non-human primate adrenal cortex. BBP-631 appears to be safe and well-tolerated in mice with 21-OHD, healthy mice and non-human primates. Taken together, these data support initiating clinical trials in adults with classic CAH due to 21-OHD. The trial will sequentially enroll individuals in up to 3 successive dose-escalation cohorts. Each subject will receive a single dose of BBP-631 and safety will be assessed prior to dose escalation. Endogenous production rates of adrenal steroids (cortisol, 17-hydroxyprogesterone, androstenedione) will be determined pre- and post- dose, and their concentrations assessed over a 1-year period after which subjects will roll over into an extension study for at least 4 years. The Phase 1 study will determine the tolerability of a single dose of BBP-631. The magnitude and durability of BBP-631 and effects on adrenal steroids, ACTH and, where relevant, aldosterone levels will be monitored. The ability of BBP-631 to allow tapering of GC doses will also be explored. This first in human study of gene therapy for CAH represents a milestone in the development of novel and improved treatment approaches for patients with classic CAH.

Long-term stability of avalanche scaling and integrative network organization in prefrontal and premotor cortex.

Ongoing neuronal activity in the brain establishes functional networks that reflect normal and pathological brain function. Most estimates of these functional networks suffer from low spatiotemporal resolution and indirect measures of neuronal population activity, limiting the accuracy and reliability in their reconstruction over time. Here, we studied the stability of neuronal avalanche dynamics and corresponding reconstructed functional networks in the adult brain. Using chronically implanted high-density microelectrode arrays, the local field potential (LFP) of resting-state activity was recorded in prefrontal and premotor cortex of awake nonhuman primates. Avalanche dynamics revealed stable scaling exhibiting an inverted parabolic profile and collapse exponent of 2 in line with a critical branching process over many days and weeks. Functional networks were based on a Bayesian-derived estimator and demonstrated stable integrative properties characterized by nontrivial high neighborhood overlap between strongly connected nodes and robustness to weak-link pruning. Entropy-based mixing analysis revealed significant changes in strong link weights over weeks. The long-term stability in avalanche scaling and integrative network organization in the face of individual link weight changes should support the development of noninvasive biomarkers to characterize normal and abnormal brain states in the adult brain.

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex

Objective. Non-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery. Approach. We present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (∼3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side and in vivo with macaques to validate the utility of our MMAD. Main results. Using our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and via in vivo imaging of blood flow from the underlying microvasculature using optical coherence tomography angiography. Significance. Our results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.

Leslie Ungerleider, 1946–2020: Who, what, and where

Leslie Ungerleider, a pioneering neuroscientist who profoundly shaped our understanding of the visual system, died unexpectedly but peacefully at her home on December 11, 2020, at the age of 74. She was the Chief of the Laboratory of Brain and Cognition at the National Institute of Mental Health and an NIH Distinguished Investigator. Despite struggling with health issues in recent years, she remained vibrant and fully engaged in science until her abrupt passing, leaving many colleagues, collaborators, and mentees in shock. Leslie’s intellectual legacy runs both deep and broad, as she made major contributions to our understanding of the functional organization of the visual cortex in humans and nonhuman primates using a combination of neuroanatomical, neurophysiological, neuroimaging, and behavioral methods. Leslie is best known for demonstrating that the primate visual cortex contains separate neural systems for perceiving “what” things are and “where” they are located. Leslie Ungerleider. Image credit: Michael Beauchamp (Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA). Leslie was an ardent supporter of women in neuroscience and was a highly inspirational role model, starting at a time when there were far fewer female senior neuroscientists than in the present day. In her many leadership positions across multiple scientific organizations, she was a passionate advocate for women. More broadly, the depth to which she influenced those she mentored, collaborated, or interacted closely with revealed itself in the outpouring of sentiment in the days immediately following her passing (1). Leslie was not only a brilliant and influential scientist, but equally notably, she deeply cared about all of her laboratory members as well as the community, and was gifted in communicating at all levels. She fully engaged with whomever she was talking with and suffered the details to get all aspects of doing science right, from the experimental … [↵][1]1To whom correspondence may be addressed. Email: vanessen{at}wustl.edu. [1]: #xref-corresp-1-1

Abstract P791: A Lesion-Based Toolbox to Study Ischemic Stroke in Primates

The primate cortex is a highly complex structure responsible for a variety of sophisticated tasks and behaviors including long-term memory storage, sensation, movement, and vision. However, little is understood with respect to the underlying cortical physiology and dynamics following injury. It is essential that these phenomena are studied in a model which shares a high degree of complexity and evolutionary history with human cortex: the non-human primate (NHP) cortex. Such studies would allow for the development of improved tools and strategies for treating neurological disorders such as stroke. However, current methods of inducing cortical lesions in NHP pre-clinical studies often require surgical skill, produce variable results, and lack controllability of lesion size and location. Methods: To address these challenges for the development of effective therapies, we developed a versatile lesion-based toolbox for studying NHP cortical physiology.First, we demonstrated the photothrombotic technique, wherein intravenous infusion of a photosensitive dye followed by targeted cortical illumination leads to the formation of localized thrombi in the vasculature. With this method, we induced ischemic lesions extending through all layers of sensorimotor cortex in 5 adult macaques. To validate the disruption of blood flow in cortical microvasculature in vivo , we employed optical coherence tomography angiography (OCTA) imaging. Additionally, we implanted a semi-transparent electrocorticography array to record neural activity before, during, and after the induction of lesions. The transparency of the array enabled us to illuminate through the array to induce lesions and acquire OCTA images to register electrodes to ischemic areas in vivo . Thus, we observed the dynamics of the underlying network neural activity as lesions were developing. Histological staining validated neuronal cell death and was used to estimate lesion volumes. Finally, we developed a computational model to predict lesion sizes based on illumination parameters. In combination with behavioral findings, this toolbox can drive the development of future rehabilitative therapies for stroke at clinically relevant time scales in pre-clinical studies.

A thermal nociceptive patch in the S2 cortex of nonhuman primates: a combined functional magnetic resonance imaging and electrophysiology study.

Human functional magnetic resonance imaging (fMRI) and behavioral studies have established the roles of cortical areas along the Sylvian fissure in sensing subjective pain. Yet, little is known about how sensory aspects of painful information are represented and processed by neurons in these regions and how their electrophysiological activities are related to fMRI signals. The current study aims to partially address this critical knowledge gap by performing fMRI-guided microelectrode mapping and recording studies in the homologous region of the parietal operculum in squirrel monkeys under light anesthesia. In each animal studied (n = 8), we detected mesoscale mini-networks for heat nociception in cortical regions around the lateral sulcus. Within the network, we discovered a ∼1.5 × 1.5-mm2-sized cortical patch that solely contained heat nociceptive neurons that aligned with the heat fMRI activation locus. These neurons responded slowly to thermal (heat and cold) nociceptive stimuli exclusively, continued firing for several seconds after the succession of stimulation, and exhibited multidigit receptive fields and high spontaneous firing rates. Similar to the fMRI responses, increasing temperatures in the nociceptive range led to a nonlinear increase in firing rates. The finding of a clustering of heat nociceptive neurons provides novel insights into the unique functional organization of thermal nociception in the S2 subregion of the primate brain. With fMRI, it supports the existence of a modality-preferred heat nociceptive patch that is spatially separated and intermingled with touch patches containing neurons with comparable receptive fields and the presence of functionally distinct mini-networks in primate opercular cortex.

Selective Participation of Single Cortical Neurons in Neuronal Avalanches.

Neuronal avalanches are scale-invariant neuronal population activity patterns in the cortex that emerge in vivo in the awake state and in vitro during balanced excitation and inhibition. Theory and experiments suggest that avalanches indicate a state of cortex that improves numerous aspects of information processing by allowing for the transient and selective formation of local as well as system-wide spanning neuronal groups. If avalanches are indeed involved with information processing, one might expect that single neurons would participate in avalanche patterns selectively. Alternatively, all neurons could participate proportionally to their own activity in each avalanche as would be expected for a population rate code. Distinguishing these hypotheses, however, has been difficult as robust avalanche analysis requires technically challenging measures of their intricate organization in space and time at the population level, while also recording sub- or suprathreshold activity from individual neurons with high temporal resolution. Here, we identify repeated avalanches in the ongoing local field potential (LFP) measured with high-density microelectrode arrays in the cortex of awake nonhuman primates and in acute cortex slices from young and adult rats. We studied extracellular unit firing in vivo and intracellular responses of pyramidal neurons in vitro. We found that single neurons participate selectively in specific LFP-based avalanche patterns. Furthermore, we show in vitro that manipulating the balance of excitation and inhibition abolishes this selectivity. Our results support the view that avalanches represent the selective, scale-invariant formation of neuronal groups in line with the idea of Hebbian cell assemblies underlying cortical information processing.

Minimally dependent activity subspaces for working memory and motor preparation in the lateral prefrontal cortex.

The lateral prefrontal cortex is involved in the integration of multiple types of information, including working memory and motor preparation. However, it is not known how downstream regions can extract one type of information without interference from the others present in the network. Here, we show that the lateral prefrontal cortex of non-human primates contains two minimally dependent low-dimensional subspaces: one that encodes working memory information, and another that encodes motor preparation information. These subspaces capture all the information about the target in the delay periods, and the information in both subspaces is reduced in error trials. A single population of neurons with mixed selectivity forms both subspaces, but the information is kept largely independent from each other. A bump attractor model with divisive normalization replicates the properties of the neural data. These results provide new insights into neural processing in prefrontal regions.

Diverse Temporal Dynamics of Repetition Suppression Revealed by Intracranial Recordings in the Human Ventral Temporal Cortex.

Repeated stimulus presentations commonly produce decreased neural responses-a phenomenon known as repetition suppression (RS) or adaptation-in ventral temporal cortex (VTC) of humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from nine human subjects implanted with intracranial electrodes in the VTC. The subjects viewed nonrepeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: 1) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower-frequency bands; 2) RS of the HFB signal is associated with lower peak magnitude (PM), lower total responses, and earlier peak responses; and 3) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.

Re-Visiting Type 1 Cannabinoid Receptor Distribution Across the Human and Non-Human Primate Cortex

Alterations in type 1 cannabinoid (CB1) receptor are implicated in psychiatric disorders such as schizophrenia. CB1 participates in both depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE), suggesting its involvement in both inhibitory and excitatory circuits. However, previous studies describing the distribution of CB1 in human and non-human primate cortex utilized antibodies that preferentially targeted CB1 at inhibitory boutons. Given CB1’s role in both DSI and DSE, understanding cell-type specific CB1 distribution may increase our insight into its regulation of excitatory-inhibitory balance. Here, we investigate CB1 distribution in both inhibitory and excitatory boutons using quantitative fluorescent microscopy.

Perisaccadic remapping: What? How? Why?

About 25 years ago, the discovery of receptive field (RF) remapping in the parietal cortex of nonhuman primates revealed that visual RFs, widely assumed to have a fixed retinotopic organization, can change position before every saccade. Measuring such changes can be deceptively difficult. As a result, studies that followed have generated a fascinating but somewhat confusing picture of the phenomenon. In this review, we describe how observations of RF remapping depend on the spatial and temporal sampling of visual RFs and saccade directions. Further, we summarize some of the theories of how remapping might occur in neural circuitry. Finally, based on neurophysiological and psychophysical observations, we discuss the ways in which remapping information might facilitate computations in downstream brain areas.