Subset Of Stimuli Research Articles

Gustatory Expression Pattern of the Human TAS2R Bitter Receptor Gene Family Reveals a Heterogenous Population of Bitter Responsive Taste Receptor Cells

Human bitter taste is mediated by approximately 25 members of the human TAS2 receptor (hTAS2R) gene family. The hTAS2R genes are expressed in taste buds of gustatory papillae on the tongue surface. Because many naturally occurring bitter compounds are toxic, bitter taste receptors are believed to serve as warning sensors against the ingestion of toxic food compounds. An important question is whether bitter taste receptor cells are a homogeneous, broadly tuned population of cells, which uniformly express all bitter taste receptor genes, or not. Gene expression analyses in rodents demonstrated an essentially overlapping expression of TAS2R genes indicating a broad tuning, whereas functional in vivo analyses suggest a narrow tuning. The present study demonstrates the expression of all 25 human TAS2R genes in taste receptor cells of human circumvallate papillae. As shown by in situ hybridization experiments, the expression of hTAS2R genes differs in both the apparent level of expression and the number of taste receptor cells expressing these genes, suggesting a heterogeneous bitter taste receptor cell population. Differences in gene expression levels were verified by quantitative reverse transcription-PCR experiments for a subset of hTAS2R genes. Direct evidence for the heterogeneity of bitter taste receptor cells is provided by dual-labeling in situ hybridizations with selected pairs of hTAS2R gene-specific probes. Functional coexpression experiments in heterologous cells show competition among hTAS2Rs, indicating a possible biological reason for the observed expression pattern. From the data, we conclude that human bitter taste receptor cells are tuned to detect a limited subset of bitter stimuli.

The induction of naming in children with no prior tact responses as a function of multiple exemplar histories of instruction.

The phenomenon identified as naming is a key stage of language function that is missing in many children with autism and other language delay diagnoses. We identified four children with autism, who, prior to the implementation of this experiment, did not have the naming repertoire (either speaker to listener or listener to speaker) and who had no tact responses for two- or three-dimensional stimuli. Tact training alone did not result in a naming repertoire or echoic-to-tact responses for these students. We then provided multiple exemplar instruction (MEI) across speaker and listener repertoires for a subset of stimuli (the teaching set) that resulted in untaught response components of naming and the capability to acquire naming after learning tacts for subsequent sets of stimuli. We used a delayed multiple-baseline probe design with stimuli counterbalanced across participants. The results showed that for all four students, mastery of tacts alone (the baseline or initial training condition) was not sufficient for the naming or echoic-to-tact repertoires to emerge. Following MEI the naming repertoire emerged for all four students for the initial set of stimuli. In addition, we tested for naming with novel stimuli that were probed prior to the MEI and naming also emerged following tact instruction alone for these sets. The results are discussed in terms of the role of naming in the incidental acquisition of verbal functions as part of the speaker-as-own-listener repertoire.

Sparse and selective odor coding by mitral/tufted neurons in the main olfactory bulb.

The mammalian olfactory system recognizes an enormous variety of odorants carrying a wide range of important behavioral cues. In the main olfactory bulb (MOB), odorants are ultimately represented through the action potential activity of mitral/tufted cells (M/Ts), whose selectivity and tuning to odorant molecules are therefore fundamental determinants of MOB sensory coding. However, the sheer number and diversity of discrete olfactory stimuli has been a major barrier to comprehensively evaluating M/T selectivity. To address this issue, we assessed M/T odorant responses in anesthetized mice to a 348-odorant panel widely and systematically distributed throughout chemical space, presented both individually and in mixtures at behaviorally relevant concentrations. We found that M/T activation by odorants was markedly selective, with neurons responding robustly, sensitively, and reliably to only a highly restricted subset of stimuli. Multiple odorants activating a single neuron commonly shared clear structural similarity, but M/T tuning also frequently extended beyond obviously defined chemical categories. Cells typically responded to effective compounds presented both individually and in mixtures, although firing rates evoked by mixtures typically showed partial suppression. Response selectivity was further confirmed in awake animals by chronic recordings of M/Ts. These data indicate that individual M/Ts encode specific odorant attributes shared by only a small fraction of compounds and imply that the MOB relays the collective molecular features of an odorant stimulus through a restricted set of M/Ts, each narrowly tuned to a particular stimulus characteristic.

Selective attention to time scales and time points during speech perception

Selective attention provides a mechanism by which people preferentially process subsets of stimuli when faced with overwhelming amounts of information. Spatially selective attention is particularly important for perceiving complex scenes in which multiple objects are presented simultaneously at distinct locations. Recent evidence indicates that temporally selective attention plays an important role in perception when more information than can be processed in detail is presented rapidly. Specifically, listeners can direct selective attention to both different levels of hierarchically organized rhythms and to distinct time points. Doing so modulates auditory evoked potentials at early perceptual stages. Additional studies show that directing temporally selective attention to hierarchical levels and specific time points affects perception of the rapidly changing acoustic features that constitute speech. Language experience and proficiency affect the skill with which adult listeners select the most relevant features and differentially process attended and unattended information in speech streams. Furthermore, developmental deficits in selective attention have been implicated in specific language impairment. These deficits can be reduced with interventions designed to improve speech perception and are accompanied by increases in receptive language scores. [Work supported by NIDCD grants R03DC008684 and F32DC005291 to LDS, R01DC005660 to David Poeppel, and R01DC00128 and R01DC00481 to Helen Neville.]

GCP60 Preferentially Interacts with a Caspase-generated Golgin-160 Fragment

Golgin-160, a ubiquitous protein in vertebrates, localizes to the cytoplasmic face of the Golgi complex. Golgin-160 has a large coiled-coil C-terminal domain and a non-coiled-coil N-terminal ("head") domain. The head domain contains important motifs, including a nuclear localization signal, a Golgi targeting domain, and three aspartates that are recognized by caspases during apoptosis. Some of the caspase cleavage products accumulate in the nucleus when overexpressed. Expression of a non-cleavable form of golgin-160 impairs apoptosis induced by some pro-apoptotic stimuli; thus cleavage of golgin-160 appears to play a role in apoptotic signaling. We used a yeast two-hybrid assay to screen for interactors of the golgin-160 head and identified GCP60 (Golgi complex-associated protein of 60 kDa). Further analysis demonstrated that GCP60 interacts preferentially with one of the golgin-160 caspase cleavage fragments (residues 140-311). This strong interaction prevented the golgin-160 fragment from accumulating in the nucleus when this fragment and GCP60 were overexpressed. In addition, cells overexpressing GCP60 were more sensitive to apoptosis induced by staurosporine, suggesting that nuclear-localized golgin-160-(140-311) might promote cell survival. Our results suggest a potential mechanism for regulating the nuclear translocation and potential functions of golgin-160 fragments.

Single Neurons in the Nucleus of the Solitary Tract Respond Selectively to Bitter Taste Stimuli

Molecular data suggest that receptors for all bitter ligands are coexpressed in the same taste receptor cells (TRCs), whereas physiological results indicate that individual TRCs respond to only a subset of bitter stimuli. It is also unclear to what extent bitter-responsive neurons are stimulated by nonbitter stimuli. To explore these issues, single neuron responses were recorded from the rat nucleus of the solitary tract (NST) during whole mouth stimulation with a variety of bitter compounds: 10 microM cycloheximide, 7 mM propylthiouracil, 10 mM denatonium benzoate, and 3 mM quinine hydrochloride at intensities matched for behavioral effectiveness. Stimuli representing the remaining putative taste qualities were also tested. Particular emphasis was given to activating taste receptors in the foliate papillae innervated by the quinine-sensitive glossopharyngeal nerve. This method revealed a novel population of bitter-best (B-best) cells with foliate receptive fields and significant selectivity for bitter tastants. Across all neurons, multidimensional scaling depicted bitter stimuli as loosely clustered yet clearly distinct from nonbitter tastants. When neurons with posterior receptive fields were analyzed alone, bitter stimuli formed a tighter cluster. Nevertheless, responses to bitter stimuli were variable across B-best neurons, with cycloheximide the most, and quinine the least frequent optimal stimulus. These results indicate heterogeneity for the processing of ionic and nonionic bitter tastants, which is dependent on receptive field. Further, they suggest that neurons selective for bitter substances could contribute to taste coding.

Clustering, seriation, and subset extraction of confusion data.

The study of confusion data is a well established practice in psychology. Although many types of analytical approaches for confusion data are available, among the most common methods are the extraction of 1 or more subsets of stimuli, the partitioning of the complete stimulus set into distinct groups, and the ordering of the stimulus set. Although standard commercial software packages can sometimes facilitate these types of analyses, they are not guaranteed to produce optimal solutions. The authors present a MATLAB *.m file for preprocessing confusion matrices, which includes fitting of the similarity-choice model. Two additional MATLAB programs are available for optimally clustering stimuli on the basis of confusion data. The authors also developed programs for optimally ordering stimuli and extracting subsets of stimuli using information from confusion matrices. Together, these programs provide several pragmatic alternatives for the applied researcher when analyzing confusion data. Although the programs are described within the context of confusion data, they are also amenable to other types of proximity data.

The Independence of Memory Traces of Attended and Unattended Stimuli

In a dichotic paradigm, duration-deviant mismatch negativity (MMN) largely reflects standard stimuli presented to the same ear as the deviant, suggesting an independent representation for each ear. We sought to assess this representation independence. Twenty-two participants, presented left (all 2000 Hz, 70-dB sound pressure level [SPL]) and right (all 800 Hz, 85-dB SPL) ear sounds, attended to 1 ear per block. A series of successive trains of 6-30 sounds were presented to each ear. Although 1 ear received short (40 ms) standard sounds, the other received an equal number of long (120 ms) standards. In the next train, the standard durations were switched between the ears. Stimulus onset asynchrony ranged from 120 to 440 ms. Duration deviants (240 ms) replaced the final standards of some trains. MMN latency simultaneously moved earlier for the ear changing from long to short standards and later for the ear changing from short to long standards. Based on a simple linear model, more than 80% of the memory trace reflected within-channel standards. We conclude that independently changeable memory traces underlie dichotic presentation. Separation of the representation for the attended subset of stimuli is proposed as core to the mechanism of sustained attention.

Role of Primate Visual Area V4 in the Processing of 3-D Shape Characteristics Defined by Disparity

We studied the responses of V4 neurons in awake, fixating monkeys to a diverse set of stereoscopic stimuli, including zero-order disparity (frontoparallel) stimuli, surfaces oriented in depth, and convex and concave shapes presented at various mean disparities. The responses of many V4 cells were significantly modulated across each of these stimulus subsets. In general, V4 cells were broadly tuned for zero-order disparity, and at any given disparity value, about four-fifths of the cells responded significantly above background. The response modulation by flat surfaces oriented in depth was significant for about one-quarter of cells, and the responses of about one-third of the cells were significantly modulated by convex or concave surfaces at various mean disparities. However, we encountered no cells that unambiguously distinguished a given three-dimensional (3-D) shape independent of mean disparity. Thus 3-D shapes defined by disparity are unlikely to be represented explicitly at the level of individual V4 cells. Nonetheless, V4 cells likely play an important role in the processing of 3-D shape characteristics defined by disparity as a part of a distributed network.

Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli

BackgroundCommon inbred mouse strains are genotypically diverse, but it is still poorly understood how this diversity relates to specific differences in behavior. To identify quantitative trait genes that influence taste behavior differences, it is critical to utilize assays that exclusively measure the contribution of orosensory cues. With a few exceptions, previous characterizations of behavioral taste sensitivity in inbred mouse strains have generally measured consumption, which can be confounded by post-ingestive effects. Here, we used a taste-salient brief-access procedure to measure taste sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6) and DBA/2J (D2) mice.ResultsB6 mice were more sensitive than D2 mice to a subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n-propylthiouracil (PROP), and MgCl2. D2 mice were more sensitive than B6 mice to the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl.ConclusionB6-D2 taste sensitivity differences indicate that differences in consumption of QHCl, PROP, MgCl2 and RUA are based on immediate orosensory cues, not post-ingestive effects. The absence of a strain difference for CYX suggests that polymorphisms in a T2R-type taste receptor shown to be differentially sensitive to CYX in vitro are unlikely to differentially contribute to the CYX behavioral response in vivo. The results of these studies point to the utility of these common mouse strains and their associated resources for investigation into the genetic mechanisms of taste.

Building Better Models of Visual Cortical Receptive Fields

Scientists usually study the receptive fields of visual cortical neurons by measuring responses to "optimal stimuli." In this issue of Neuron, Rust and colleagues have taken a promising alternative approach: build a receptive field model based on the cell responses to a stimulus subset and then use the model to predict responses to other stimuli.

An alternate scoring method for the multiple stimulus without replacement preference assessment

DeLeon and Iwata (1996) described the difficulties in applying the percentage approached scoring method to the multiple stimulus without replacement (MSWO) preference assessment relative to its application in the paired stimulus assessment. This scoring method may result in highly preferred items being misidentified as moderate or low preference. In the present study, the results of 57 MSWO assessments were scored using both the percentage approach method and a point weighting method. More items were identified as highly preferred with the point weighting method. Reinforcer assessments were conducted on a subset of stimuli judged to be high preference using the point weighting method but moderately or non-preferred when scored with the percentage approached method; all stimuli functioned as reinforcers. Copyright # 2005 John Wiley & Sons, Ltd. In the MSWO procedure (DeLeon and Iwata, 1996), a participant approaches a stimulus from a seven-item array. The item approached is not replaced in the array, resulting in items being presented in an unequal number of trials. DeLeon and Iwata evaluated potential reinforcers with a percentage approached scoring method similar to the one used in the paired stimulus preference assessment (Fisher et al., 1992), but noted that the percentage approached method may make it difficult to identify stimuli that could function as reinforcers. This scoring limitation is a result of the unequal number of opportunities to select each stimulus within and across MSWO sessions. The application of the percentage approach scoring methodology to the MSWO does not take this factor into account. In other words, the percentage approach scoring methodology as applied to the MSWO may result in false negatives, solely as a result of the scoring system. The purpose of the current study was to develop an alternate

Impaired performance of right-brain-damaged patients on a sentence anagram task

A sentence anagram task was used to examine the right cerebral hemispheres’s role in core grammatical functioning at the syntactic level. The test consisted of two subsets of stimuli involving empty categories: (a) those that required the empty category to be filled, and (b) those that allowed the category to remain empty. Three hypotheses were presented: (1) right-brain-damaged patients (RBDs) would be more sensitive to subset (a) than (b), (2) RBDs would perform similarly to left-brain-damaged subjects, and (3) non-brain-damaged controls would outerperform both brain-damaged groups. With all hypotheses supported, the discussion focuses on an explanation for RBDs’ sensitivity to the first subset of stimuli.

Temporal dynamics of shape analysis in macaque visual area V2.

The firing rate of visual cortical neurons typically changes substantially during a sustained visual stimulus. To assess whether, and to what extent, the information about shape conveyed by neurons in visual area V2 changes over the course of the response, we recorded the responses of V2 neurons in awake, fixating monkeys while presenting a diverse set of static shape stimuli within the classical receptive field. We analyzed the time course of various measures of responsiveness and stimulus-related response modulation at the level of individual cells and of the population. For a majority of V2 cells, the response modulation was maximal during the initial transient response (40-80 ms after stimulus onset). During the same period, the population response was relatively correlated, in that V2 cells tended to respond similarly to specific subsets of stimuli. Over the ensuing 80-100 ms, the signal-to-noise ratio of individual cells generally declined, but to a lesser degree than the evoked-response rate during the corresponding time bins, and the response profiles became decorrelated for many individual cells. Concomitantly, the population response became substantially decorrelated. Our results indicate that the information about stimulus shape evolves dynamically and relatively rapidly in V2 during static visual stimulation in ways that may contribute to form discrimination.

Information processing and reasoning with premises that are empirically false: interference, working memory, and processing speed.

In this study, we looked at the contributions of individual differences in susceptibility to interference and working memory to logical reasoning with premises that were empirically false (i.e., not necessarily true). A total of 97 university students were given a sentence completion task for which a subset of stimuli was designed to generate inappropriate semantic activation that interfered with the correct response, a measure of working memory capacity, and a series of logical reasoning tasks with premises that were not always true. The results indicate that susceptibility to interference, as measured by the error rate on the relevant subset of the sentence completion task, and working memory independently account for variation in reasoning performance. The participants who made more errors in the relevant portion of the sentence completion task also showed more empirical intrusions in the deductive reasoning task, even when the effects of working memory were partialed out. Working memory capacity was more clearly related to processes involved in generating uncertainty responses to inferences for which there was no certain conclusion. A comparison of the results of this study with studies of children's reasoning suggests that adults are capable of more selective executive processes than are children. An analysis of latency measures on the sentence completion task indicated that high working memory participants who made no errors on the sentence completion task used a strategy that involved slower processing speed, as compared with participants with similar levels of working memory who did make errors. In contrast, low working memory participants who made no errors on the sentence completion task had relatively shorter reaction times than did comparable participants who did make errors.

Precise Development of Functional and Anatomical Columns in the Neocortex

Sensory cortex is ordered into columns, each tuned to a subset of peripheral stimuli. To identify the principles underlying the construction of columnar architecture, we monitored the development of circuits in the rat barrel cortex, using laser-scanning photostimulation analysis of synaptic connectivity, reconstructions of axonal arbors, and in vivo whole-cell recording. Circuits impinging onto layer 2/3 neurons from layers 4 and 2/3 developed in a monotonic, precise progression, with little evidence for transient hyperinnervation at the level of cortical columns. Consistent with this, synaptic currents measured in layer 2/3 neurons at PND 8, just after these neurons ceased to migrate, revealed already spatially well-tuned receptive fields.

Color mechanisms used in selecting stimuli for attention and making discriminations

Previous work (Nagy & Thomas, 2003) showed that signals in different Cardinal color mechanisms could be combined to facilitate search for a color target. Further investigation (Nagy et al., 2003) suggested that signals in one Cardinal color mechanism were used to select a subset of stimuli to be attended, while signals in second Cardinal mechanism were used to discriminate the stimuli within the selected subset. In the studies described below, we asked if observers could use color mechanisms tuned to directions other than the Cardinal directions to select and discriminate stimuli. Observers searched for a single target stimulus that differed in chromaticity from nine distractor stimuli. A two-alternative forced-choice procedure was used to estimate thresholds. Results were consistent with the hypothesis that color mechanisms tuned to many different directions in color space mediate discrimination, but suggest that only signals in Cardinal mechanisms can be used to select stimuli for attention. Results imply that the selection of stimuli for attention on the basis of color may be mediated at the level of the lateral geniculate nucleus (LGN).

Spoken word to picture matching from PALPA: A critique and some new matched sets

Background: PALPA (Psycholinguistic Assessments of Language Processing in Aphasia; Kay, Lesser, & Coltheart, 1992) is a widely used clinical and research tool. Subtest 47, Spoken word–picture matching, requires the individual with aphasia to listen to a spoken word and correctly choose from five distractor pictures (target, close semantic, distant semantic, visually related, and semantically unrelated). It contributes diagnostically to the clinical evaluation of semantic processing. The authors claim that, first, errors on this test indicate that a semantic comprehension problem is present, and second, that distractor choice reflects the semantic specificity of the problem. For accurate clinical assessment the validity of these claims must be evaluated.Aims: This paper aims to evaluate the internal validity of PALPA spoken word–picture matching. It addresses two questions; first, is the relationship between the target and distractors what the authors claim it to be? Second, what is the relationship between the target and distractor stimuli in relation to a number of psycholinguistic variables? In addition it allows the clinician to examine the effects of individual variables on performance by including matched subsets of stimuli from this test (matched across five psycholinguistic variables: frequency, imageability, number of phonemes, semantic and visual similarity, word association).Methods and Procedures: Target and distractor relationships were investigated (in terms of semantic and visual similarity and word category) and psycholinguistic variables (including word frequency, word association, imageability, number of phonemes, semantic and visual similarity).Outcomes and Results: Analysis revealed a number of confounds within this test: close semantic distractors were not only more semantically similar but also more visually similar to their targets than distant semantic distractors; the semantic and visual (SV) close semantic distractors were more semantically similar to their targets than the non‐SV close semantic distractors; targets and distractors did not bear a consistent categorical relationship to their targets, and there were significant intercorrelations between variables for these stimuli (e.g., frequency and length; semantic/visual similarity and length).Conclusions: The authors' claim that this test assesses semantic comprehension is certainly still tenable. Individuals making errors on this test have a high probability of some semantic processing deficit. However, this study shows that the test fails to assess the nature of the semantic processing deficit, as error patterns are subject to the effect of confounding factors. In its current form clinicians should exercise caution when interpreting test findings and be aware of its limitations. The development, here, of matched subsets of stimuli allows performance to be re‐evaluated in terms of the influence of semantic and visual similarity, imageability, frequency, word length, and word association.

Visual search and attention: An overview

This special feature issue is devoted to attention and visual search. Attention is a central topic in psychology and visual search is both a versatile paradigm for the study of visual attention and a topic of study in itself. Visual search depends on sensory, perceptual, and cognitive processes. As a result, the search paradigm has been used to investigate a diverse range of phenomena. Manipulating the search task can vary the demands on attention. In turn, attention modulates visual search by selecting and limiting the information available at various levels of processing. Focusing on the intersection of attention and search provides a relatively structured window into the wide world of attentional phenomena. In particular, the effects of divided attention are illustrated by the effects of set size (the number of stimuli in a display) and the effects of selective attention are illustrated by cueing subsets of stimuli within the display. These two phenomena provide the starting point for the articles in this special issue. The articles are organized into four general topics to help structure the issues of attention and search.

Heterogeneous Modulation of Place Cell Firing by Changes in Context

Hippocampal place cells show spatially localized activity that can be modulated by both geometric information (e.g., the distances and directions of features in the environment) and nongeometric information (e.g., colors, odors, and possibly behaviors). Nongeometric information may allow the discrimination of different spatial contexts. Understanding how nongeometric (or contextual) information affects hippocampal activity is important in light of proposals that the hippocampus may play a role in constructing a representation of spatial context. We investigated the contextual modulation of place cell activity by recording hippocampal place cells while rats foraged in compound contexts comprising black or white color paired with lemon or vanilla odor. Some cells responded to the color or odor changes alone, but most responded to varying combinations of both. Thus, we demonstrate, for the first time, that there is a heterogeneous input by contextual inputs into the hippocampus. We propose a model of contextual remapping of place cells in which the geometric inputs are selectively activated by subsets of contextual stimuli. Because it appears that different place cells are affected by different subsets of contextual stimuli, the representation of the entire context would require activity at the population level, supporting a role for the hippocampus in constructing a representation of spatial context.