Browsing by Subject "Macaca mulatta"
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Item Open Access A pathway in primate brain for internal monitoring of movements.(Science, 2002-05-24) Sommer, Marc A; Wurtz, Robert HIt is essential to keep track of the movements we make, and one way to do that is to monitor correlates, or corollary discharges, of neuronal movement commands. We hypothesized that a previously identified pathway from brainstem to frontal cortex might carry corollary discharge signals. We found that neuronal activity in this pathway encodes upcoming eye movements and that inactivating the pathway impairs sequential eye movements consistent with loss of corollary discharge without affecting single eye movements. These results identify a pathway in the brain of the primate Macaca mulatta that conveys corollary discharge signals.Item Open Access A polyaxonal amacrine cell population in the primate retina.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014-03) Greschner, Martin; Field, Greg D; Li, Peter H; Schiff, Max L; Gauthier, Jeffrey L; Ahn, Daniel; Sher, Alexander; Litke, Alan M; Chichilnisky, EJAmacrine cells are the most diverse and least understood cell class in the retina. Polyaxonal amacrine cells (PACs) are a unique subset identified by multiple long axonal processes. To explore their functional properties, populations of PACs were identified by their distinctive radially propagating spikes in large-scale high-density multielectrode recordings of isolated macaque retina. One group of PACs exhibited stereotyped functional properties and receptive field mosaic organization similar to that of parasol ganglion cells. These PACs had receptive fields coincident with their dendritic fields, but much larger axonal fields, and slow radial spike propagation. They also exhibited ON-OFF light responses, transient response kinetics, sparse and coordinated firing during image transitions, receptive fields with antagonistic surrounds and fine spatial structure, nonlinear spatial summation, and strong homotypic neighbor electrical coupling. These findings reveal the functional organization and collective visual signaling by a distinctive, high-density amacrine cell population.Item Open Access A Refined Neuronal Population Measure of Visual Attention.(PloS one, 2015-01) Mayo, J Patrick; Cohen, Marlene R; Maunsell, John HRNeurophysiological studies of cognitive mechanisms such as visual attention typically ignore trial-by-trial variability and instead report mean differences averaged across many trials. Advances in electrophysiology allow for the simultaneous recording of small populations of neurons, which may obviate the need for averaging activity over trials. We recently introduced a method called the attention axis that uses multi-electrode recordings to provide estimates of attentional state of behaving monkeys on individual trials. Here, we refine this method to eliminate problems that can cause bias in estimates of attentional state in certain scenarios. We demonstrate the sources of these problems using simulations and propose an amendment to the previous formulation that provides superior performance in trial-by-trial assessments of attentional state.Item Open Access Activity of neurons in monkey globus pallidus during oculomotor behavior compared with that in substantia nigra pars reticulata.(J Neurophysiol, 2010-04) Shin, SooYoon; Sommer, Marc AThe basal ganglia are a subcortical assembly of nuclei involved in many aspects of behavior. Three of the nuclei have high firing rates and inhibitory influences: the substantia nigra pars reticulata (SNr), globus pallidus interna (GPi), and globus pallidus externa (GPe). The SNr contains a wide range of visual, cognitive, and motor signals that have been shown to contribute to saccadic eye movements. Our hypothesis was that GPe and GPi neurons carry similarly diverse signals during saccadic behavior. We recorded from GPe, GPi, and SNr neurons in monkeys that made memory-guided saccades and found that neurons in all three structures had increases or decreases in activity synchronized with saccade generation, visual stimulation, or reward. Comparing GPe neurons with GPi neurons, we found relatively more visual-related activity in GPe and more reward-related activity in GPi. Comparing both pallidal samples with the SNr, we found a greater resemblance between GPe and SNr neurons than that between GPi and SNr neurons. As expected from a known inhibitory projection from GPe to SNr, there was a general reversal of sign in activity modulations between the structures: bursts of activity were relatively more common in GPe and pauses more common in SNr. We analyzed the response fields of neurons in all three structures and found relatively narrow and lateralized fields early in trials (during visual and saccadic events) followed by a broadening later in trials (during reward). Our data reinforce an emerging, new consensus that the GPe and GPi, in addition to the SNr, contribute to oculomotor behavior.Item Open Access Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells.(Frontiers in immunology, 2021-01) Song, Shengli; Manook, Miriam; Kwun, Jean; Jackson, Annette M; Knechtle, Stuart J; Kelsoe, GarnettAntibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC) mismatches are especially problematic. Most research directed towards the management of clinical AMR has focused on identifying and characterizing circulating donor-specific HLA antibody (DSA) and optimizing therapies that reduce B-cell activation and/or block antibody secretion by inhibiting plasmacyte survival. Here we describe a novel set of reagents and techniques to allow more specific measurements of MHC sensitization across different animal transplant models. Additionally, we have used these approaches to isolate and clone individual HLA-specific B cells from patients sensitized by pregnancy or transplantation. We have identified and characterized the phenotypes of individual HLA-specific B cells, determined the V(D)J rearrangements of their paired H and L chains, and generated recombinant antibodies to determine affinity and specificity. Knowledge of the BCR genes of individual HLA-specific B cells will allow identification of clonally related B cells by high-throughput sequence analysis of peripheral blood mononuclear cells and permit us to re-construct the origins of HLA-specific B cells and follow their somatic evolution by mutation and selection.Item Open Access Anatomical identification of extracellularly recorded cells in large-scale multielectrode recordings.(J Neurosci, 2015-03-18) Li, Peter H; Gauthier, Jeffrey L; Schiff, Max; Sher, Alexander; Ahn, Daniel; Field, Greg D; Greschner, Martin; Callaway, Edward M; Litke, Alan M; Chichilnisky, EJThis study combines for the first time two major approaches to understanding the function and structure of neural circuits: large-scale multielectrode recordings, and confocal imaging of labeled neurons. To achieve this end, we develop a novel approach to the central problem of anatomically identifying recorded cells, based on the electrical image: the spatiotemporal pattern of voltage deflections induced by spikes on a large-scale, high-density multielectrode array. Recordings were performed from identified ganglion cell types in the macaque retina. Anatomical images of cells in the same preparation were obtained using virally transfected fluorescent labeling or by immunolabeling after fixation. The electrical image was then used to locate recorded cell somas, axon initial segments, and axon trajectories, and these signatures were used to identify recorded cells. Comparison of anatomical and physiological measurements permitted visualization and physiological characterization of numerically dominant ganglion cell types with high efficiency in a single preparation.Item Open Access Auditory signals evolve from hybrid- to eye-centered coordinates in the primate superior colliculus.(Journal of neurophysiology, 2012-07) Lee, Jungah; Groh, Jennifer MVisual and auditory spatial signals initially arise in different reference frames. It has been postulated that auditory signals are translated from a head-centered to an eye-centered frame of reference compatible with the visual spatial maps, but, to date, only various forms of hybrid reference frames for sound have been identified. Here, we show that the auditory representation of space in the superior colliculus involves a hybrid reference frame immediately after the sound onset but evolves to become predominantly eye centered, and more similar to the visual representation, by the time of a saccade to that sound. Specifically, during the first 500 ms after the sound onset, auditory response patterns (N = 103) were usually neither head nor eye centered: 64% of neurons showed such a hybrid pattern, whereas 29% were more eye centered and 8% were more head centered. This differed from the pattern observed for visual targets (N = 156): 86% were eye centered, <1% were head centered, and only 13% exhibited a hybrid of both reference frames. For auditory-evoked activity observed within 20 ms of the saccade (N = 154), the proportion of eye-centered response patterns increased to 69%, whereas the hybrid and head-centered response patterns dropped to 30% and <1%, respectively. This pattern approached, although did not quite reach, that observed for saccade-related activity for visual targets: 89% were eye centered, 11% were hybrid, and <1% were head centered (N = 162). The plainly eye-centered visual response patterns and predominantly eye-centered auditory motor response patterns lie in marked contrast to our previous study of the intraparietal cortex, where both visual and auditory sensory and motor-related activity used a predominantly hybrid reference frame (Mullette-Gillman et al. 2005, 2009). Our present findings indicate that auditory signals are ultimately translated into a reference frame roughly similar to that used for vision, but suggest that such signals might emerge only in motor areas responsible for directing gaze to visual and auditory stimuli.Item Open Access Coherence potentials: loss-less, all-or-none network events in the cortex.(PLoS Biol, 2010-01-12) Thiagarajan, Tara C; Lebedev, Mikhail A; Nicolelis, Miguel A; Plenz, DietmarTransient associations among neurons are thought to underlie memory and behavior. However, little is known about how such associations occur or how they can be identified. Here we recorded ongoing local field potential (LFP) activity at multiple sites within the cortex of awake monkeys and organotypic cultures of cortex. We show that when the composite activity of a local neuronal group exceeds a threshold, its activity pattern, as reflected in the LFP, occurs without distortion at other cortex sites via fast synaptic transmission. These large-amplitude LFPs, which we call coherence potentials, extend up to hundreds of milliseconds and mark periods of loss-less spread of temporal and amplitude information much like action potentials at the single-cell level. However, coherence potentials have an additional degree of freedom in the diversity of their waveforms, which provides a high-dimensional parameter for encoding information and allows identification of particular associations. Such nonlinear behavior is analogous to the spread of ideas and behaviors in social networks.Item Open Access Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.(Journal of virology, 2016-05) Nelson, Cody S; Pollara, Justin; Kunz, Erika L; Jeffries, Thomas L; Duffy, Ryan; Beck, Charles; Stamper, Lisa; Wang, Minyue; Shen, Xiaoying; Pickup, David J; Staats, Herman F; Hudgens, Michael G; Kepler, Thomas B; Montefiori, David C; Moody, M Anthony; Tomaras, Georgia D; Liao, Hua-Xin; Haynes, Barton F; Ferrari, Guido; Fouda, Genevieve GA; Permar, Sallie RUnlabelled
Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding.Importance
Efforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT.Item Open Access Compensatory saccades made to remembered targets following orbital displacement by electrically stimulating the dorsomedial frontal cortex or frontal eye fields of primates.(Brain Res, 1996-07-15) Tehovnik, EJ; Sommer, MAIf the eye-position signal during visually-evoked saccades is dependent on the dorsomedial frontal cortex (DMFC), one would expect that saccades generated to briefly presented visual targets would be disrupted after displacement of the eyes via electrical stimulation of this cortical area. Compared are compensatory saccades evoked to brief targets following stimulation of the DMFC and frontal eye fields (FEF). Compensatory saccades produced to brief targets following perturbation via the DMFC were not affected. Accordingly, electrical stimulation of the DMFC does not disrupt the eye-position signal during the execution of visually-evoked saccades.Item Open Access Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus.(J Neurophysiol, 2000-04) Sommer, MA; Wurtz, RHThe frontal eye field (FEF) and superior colliculus (SC) contribute to saccadic eye movement generation, and much of the FEF's oculomotor influence may be mediated through the SC. The present study examined the composition and topographic organization of signals flowing from FEF to SC by recording from FEF neurons that were antidromically activated from rostral or caudal SC. The first and most general result was that, in a sample of 88 corticotectal neurons, the types of signals relayed from FEF to SC were highly diverse, reflecting the general population of signals within FEF rather than any specific subset of signals. Second, many neurons projecting from FEF to SC carried signals thought to reflect cognitive operations, namely tonic discharges during the delay period of a delayed-saccade task (delay signals), elevated discharges during the gap period of a gap task (gap increase signals), or both. Third, FEF neurons discharging during fixation were found to project to the SC, although they did not project preferentially to rostral SC, where similar fixation neurons are found. Neurons that did project preferentially to the rostral SC were those with foveal visual responses and those pausing during the gap period of the gap task. Many of the latter neurons also had foveal visual responses, presaccadic pauses in activity, and postsaccadic increases in activity. These two types of rostral-projecting neurons therefore may contribute to the activity of rostral SC fixation neurons. Fourth, conduction velocity was used as an indicator of cell size to correct for sampling bias. The outcome of this correction procedure suggested that among the most prevalent neurons in the FEF corticotectal population are those carrying putative cognitive-related signals, i.e., delay and gap increase signals, and among the least prevalent are those carrying presaccadic burst discharges but lacking peripheral visual responses. Fifth, corticotectal neurons carrying various signals were biased topographically across the FEF. Neurons with peripheral visual responses but lacking presaccadic burst discharges were biased laterally, neurons with presaccadic burst discharges but lacking peripheral visual responses were biased medially, and neurons carrying delay or gap increase signals were biased dorsally. Finally, corticotectal neurons were distributed within the FEF as a function of their visual or movement field eccentricity and projected to the SC such that eccentricity maps in both structures were closely aligned. We conclude that the FEF most likely influences the activity of SC neurons continuously from the start of fixation, through visual analysis and cognitive manipulations, until a saccade is generated and fixation begins anew. Furthermore, the projection from FEF to SC is highly topographically organized in terms of function at both its source and its termination.Item Open Access Correlated firing among major ganglion cell types in primate retina.(The Journal of physiology, 2011-01) Greschner, Martin; Shlens, Jonathon; Bakolitsa, Constantina; Field, Greg D; Gauthier, Jeffrey L; Jepson, Lauren H; Sher, Alexander; Litke, Alan M; Chichilnisky, EJRetinal ganglion cells exhibit substantial correlated firing: a tendency to fire nearly synchronously at rates different from those expected by chance. These correlations suggest that network interactions significantly shape the visual signal transmitted from the eye to the brain. This study describes the degree and structure of correlated firing among the major ganglion cell types in primate retina. Correlated firing among ON and OFF parasol, ON and OFF midget, and small bistratified cells, which together constitute roughly 75% of the input to higher visual areas, was studied using large-scale multi-electrode recordings. Correlated firing in the presence of constant, spatially uniform illumination exhibited characteristic strength, time course and polarity within and across cell types. Pairs of nearby cells with the same light response polarity were positively correlated; cells with the opposite polarity were negatively correlated. The strength of correlated firing declined systematically with distance for each cell type, in proportion to the degree of receptive field overlap. The pattern of correlated firing across cell types was similar at photopic and scotopic light levels, although additional slow correlations were present at scotopic light levels. Similar results were also observed in two other retinal ganglion cell types. Most of these observations are consistent with the hypothesis that shared noise from photoreceptors is the dominant cause of correlated firing. Surprisingly, small bistratified cells, which receive ON input from S cones, fired synchronously with ON parasol and midget cells, which receive ON input primarily from L and M cones. Collectively, these results provide an overview of correlated firing across cell types in the primate retina, and constraints on the underlying mechanisms.Item Open Access Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection.(Am J Transplant, 2014-01) Kim, EJ; Kwun, J; Gibby, AC; Hong, JJ; Farris III, AB; Iwakoshi, NN; Villinger, F; Kirk, AD; Knechtle, SJDe novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Previously, we demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus and alefacept (AMR regimen) reliably induced early DSA production with AMR in a nonhuman primate kidney transplant model. Five animals were assigned as positive AMR controls, four received additional belatacept and four received additional anti-CD40 mAb (2C10R4). Notably, production of early de novo DSA was completely attenuated with additional belatacept or 2C10R4 treatment. In accordance with this, while positive controls experienced a decrease in peripheral IgM(+) B cells, bela- and 2C10R4-added groups maintained a predominant population of IgM(+) B cells, potentially indicating decreased isotype switching. Central memory T cells (CD4(+) CD28(+) CD95(+)) as well as PD-1(hi) CD4(+) T cells were decreased in both bela-added and 2C10R4-added groups. In analyzing germinal center (GC) reactions in situ, lymph nodes further revealed a reduction of B cell clonal expansion, GC-follicular helper T (Tfh) cells, and IL-21 production inside GCs with additional belatacept or 2C10R4 treatment. Here we provide evidence that belatacept and 2C10R4 selectively suppresses the humoral response via regulating Tfh cells and prevents AMR in this nonhuman primate model.Item Open Access Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum.(J Neurophysiol, 2013-04) Ashmore, Robin C; Sommer, Marc AThe caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce "delay activity" between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move.Item Open Access Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.(Frontiers in cellular and infection microbiology, 2020-01) Aid, Malika; Ram, Daniel R; Bosinger, Steven E; Barouch, Dan H; Reeves, R KeithNatural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in any NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP.Item Open Access Division of labor in frontal eye field neurons during presaccadic remapping of visual receptive fields.(J Neurophysiol, 2012-10) Shin, Sooyoon; Sommer, Marc AOur percept of visual stability across saccadic eye movements may be mediated by presaccadic remapping. Just before a saccade, neurons that remap become visually responsive at a future field (FF), which anticipates the saccade vector. Hence, the neurons use corollary discharge of saccades. Many of the neurons also decrease their response at the receptive field (RF). Presaccadic remapping occurs in several brain areas including the frontal eye field (FEF), which receives corollary discharge of saccades in its layer IV from a collicular-thalamic pathway. We studied, at two levels, the microcircuitry of remapping in the FEF. At the laminar level, we compared remapping between layers IV and V. At the cellular level, we compared remapping between different neuron types of layer IV. In the FEF in four monkeys (Macaca mulatta), we identified 27 layer IV neurons with orthodromic stimulation and 57 layer V neurons with antidromic stimulation from the superior colliculus. With the use of established criteria, we classified the layer IV neurons as putative excitatory (n = 11), putative inhibitory (n = 12), or ambiguous (n = 4). We found that just before a saccade, putative excitatory neurons increased their visual response at the RF, putative inhibitory neurons showed no change, and ambiguous neurons increased their visual response at the FF. None of the neurons showed presaccadic visual changes at both RF and FF. In contrast, neurons in layer V showed full remapping (at both the RF and FF). Our data suggest that elemental signals for remapping are distributed across neuron types in early cortical processing and combined in later stages of cortical microcircuitry.Item Open Access Dynamics of visual receptive fields in the macaque frontal eye field.(J Neurophysiol, 2015-12) Mayo, J Patrick; DiTomasso, Amie R; Sommer, Marc A; Smith, Matthew ANeuronal receptive fields (RFs) provide the foundation for understanding systems-level sensory processing. In early visual areas, investigators have mapped RFs in detail using stochastic stimuli and sophisticated analytical approaches. Much less is known about RFs in prefrontal cortex. Visual stimuli used for mapping RFs in prefrontal cortex tend to cover a small range of spatial and temporal parameters, making it difficult to understand their role in visual processing. To address these shortcomings, we implemented a generalized linear model to measure the RFs of neurons in the macaque frontal eye field (FEF) in response to sparse, full-field stimuli. Our high-resolution, probabilistic approach tracked the evolution of RFs during passive fixation, and we validated our results against conventional measures. We found that FEF neurons exhibited a surprising level of sensitivity to stimuli presented as briefly as 10 ms or to multiple dots presented simultaneously, suggesting that FEF visual responses are more precise than previously appreciated. FEF RF spatial structures were largely maintained over time and between stimulus conditions. Our results demonstrate that the application of probabilistic RF mapping to FEF and similar association areas is an important tool for clarifying the neuronal mechanisms of cognition.Item Open Access Effective spread and timecourse of neural inactivation caused by lidocaine injection in monkey cerebral cortex.(J Neurosci Methods, 1997-06-06) Tehovnik, EJ; Sommer, MAWe studied the effective spread of lidocaine to inactivate neural tissue in the frontal cortex of the rhesus monkey. Injections of 2% lidocaine at 4 microl/min were made while units were recorded 1 or 2 mm away. To inactivate units 1 mm away from the injection site 100% of the time, 7 microl of lidocaine had to be injected. To inactivate units 2 mm away from the injection site 100% of the time, 30 microl of lidocaine were required. Units were maximally inactivated around 8 min after the start of a lidocaine injection, and they gradually recovered, regaining most of their initial activity by around 30 min after the start of an injection. The volume of lidocaine required to inactivate neurons > 90% of the time could be estimated by the spherical volume equation, V = 4/3 pi (r)3. To prolong the inactivation, a slower infusion of lidocaine subsequent to an initial bolus was effective. Saline control injections had no effect. These results allow both a prediction of the timecourse of neural inactivation and an estimate of the spread of neural inactivation following injection of lidocaine into the monkey cerebral cortex.Item Open Access Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016-05) Pages, Daniel S; Ross, Deborah A; Puñal, Vanessa M; Agashe, Shruti; Dweck, Isaac; Mueller, Jerel; Grill, Warren M; Wilson, Blake S; Groh, Jennifer MUnderstanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 μA, 100-300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts.Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants.Item Open Access Efficient coding of spatial information in the primate retina.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012-11) Doi, Eizaburo; Gauthier, Jeffrey L; Field, Greg D; Shlens, Jonathon; Sher, Alexander; Greschner, Martin; Machado, Timothy A; Jepson, Lauren H; Mathieson, Keith; Gunning, Deborah E; Litke, Alan M; Paninski, Liam; Chichilnisky, EJ; Simoncelli, Eero PSensory neurons have been hypothesized to efficiently encode signals from the natural environment subject to resource constraints. The predictions of this efficient coding hypothesis regarding the spatial filtering properties of the visual system have been found consistent with human perception, but they have not been compared directly with neural responses. Here, we analyze the information that retinal ganglion cells transmit to the brain about the spatial information in natural images subject to three resource constraints: the number of retinal ganglion cells, their total response variances, and their total synaptic strengths. We derive a model that optimizes the transmitted information and compare it directly with measurements of complete functional connectivity between cone photoreceptors and the four major types of ganglion cells in the primate retina, obtained at single-cell resolution. We find that the ganglion cell population exhibited 80% efficiency in transmitting spatial information relative to the model. Both the retina and the model exhibited high redundancy (~30%) among ganglion cells of the same cell type. A novel and unique prediction of efficient coding, the relationships between projection patterns of individual cones to all ganglion cells, was consistent with the observed projection patterns in the retina. These results indicate a high level of efficiency with near-optimal redundancy in visual signaling by the retina.