Recognition Of Novel Objects Research Articles

Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1-RAGE Axis Mediation.

We evaluated the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on behavioral and cognitive function in a mouse model of mild subarachnoid hemorrhage (SAH) and explored the underlying mechanisms in conjunction with the HMGB1-RAGE axis. The SAH models were generated in a total of 126 male C57BL/6J mice via endovascular perforation and evaluated 24 h and 72 h after the intravenous administration of BMSCs (3 × 105 cells). The BMSCs were administered once, at 3 h, or twice, at 3 h and 48 h after the model induction. The therapeutic effects of the BMSCs were compared to those of the saline administration. Compared to saline-treated SAH-model mice, at 3 h, the mice with mild SAH treated with the BMSCs showed significant improvements in their neurological scores and cerebral edema. The administration of the BMSCs decreased the mRNA expression of HMGB1, RAGE, TLR4, and MyD88, as well as the protein expression of HMGB1 and phosphorylated NF-kB p65. Furthermore, the numbers of slips per walking time, impairments in short-term memory, and the recognition of novel objects were improved. There was some improvement in inflammatory-marker levels and cognitive function according to the BMSCs' administration times, but no large differences were seen. The administration of BMSCs improved behavioral and cognitive dysfunction by ameliorating HMGB1-RAGE axis-mediated neuroinflammation after SAH.

Reduced Reelin Expression Induces Memory Deficits through Dab-1/ NMDAR Signaling Pathway: Cronobacter sakazakii Infection in a Rat Model of Experimental Meningitis

The purpose of this study was to examine whether the Cronobacter sakazakii infection-induced inflammation alters the Reelin signaling pathway that is involved in learning and memory. To test this, postnatal day (PND)-15 rat pups were either treated with Luria Bertani broth/Escherichia coli OP50/C. sakazakii through oral gavage or maintained as control and allowed to stay with their mothers until PND-24. Experimental groups’ rats were subjected to long-term novel object recognition test during their adolescent age PND-30–32. Observed behavioral data showed that C. sakazakii infection causes a deficit in recognition of novel objects from known objects. Further, our analysis showed that C. sakazakii infection-mediated inflammation decreases the Reelin expression by proteolytic cleavage and alters its receptor apolipoprotein E-receptor (ApoER)-2 splice variants ApoER2 (ex19) and ApoER2 (Δ). Subsequently, downregulated Reelin alters the phosphorylation of disabled adapter protein (Dab)-1 and leads to differential expression of N-methyl-D-aspartate (NMDA) receptor subunits 2A and 2B. Further, the NMDA receptor influences the expression of postsynaptic density (PSD)-95 protein and brain-derived neurotrophic factor (BDNF). Observed results suggest a deficit in recognition of novel objects possibly due to the alternation in Reelin signaling pathway.

Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice

With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has anti-neuroinflammation effects by modulating microglial polarization and inhibiting astrocyte activation. In this study, we demonstrated that the inhalation of 1.3% isoflurane (a sub-minimal alveolar concentration, sub-MAC) for 6 h impaired recognition of novel objects from Day 1 to Day3 in adult mice. Prolonged sub-MAC isoflurane exposure also triggered typically reactive microglia and A1-like astrocytes in the hippocampus of adult mice on Day 3 after anesthesia. In addition, prolonged isoflurane inhalation switched microglia into a proinflammatory M1 phenotype characterized by elevated CD68 and iNOS as well as decreased arginase-1 and IL-10. Metformin pretreatment before anesthesia enhanced cognitive performance in the novel object test. The positive cellular modifications promoted by metformin pretreatment included the inhibition of reactive microglia and A1-like astrocytes and the polarization of microglia into M2 phenotype in the hippocampus of adult mice. In conclusion, prolonged sub-MAC isoflurane exposure triggered significant hippocampal neuroinflammation and cognitive decline in adult mice which can be alleviated by metformin pretreatment via inhibiting reactive microglia and A1-like astrocytes and promoting microglia polarization toward anti-inflammatory phenotype in the hippocampus.

Cross attention redistribution with contrastive learning for few shot object detection

Few-shot object detection aims to learn to detect novel objects from only a few annotated samples. Most training frameworks adopt the fusing of high-dimensional features with semantic information on the support images to learn the recognition and localization process of novel objects on the query images. Most prior works directly use a cross-correlation mechanism to integrate semantic information from support features. However, such operations will introduce noise to the query features, confusing the generation of region proposals and affecting the final localization precision. In this paper, we focus on sufficient mining and integrating the support features conducive to generating regional proposals to improve further the stability and accuracy of the few-shot object detector. We propose a cross-attention redistribution (CAReD) module to adaptively integrate support features into query features, effectively removing harmful support features and enhancing the regional features of novel categories. In addition, to classify the novel instances accurately, it is necessary to minimize the intra-class distance while maximizing the inter-class distance. To this end, this paper proposes a network training strategy based on contrastive learning, which can better supervise the training process of CAReD and, more importantly, can effectively improve the classification precision for bounding boxes. Experiments on Pascal VOC and MS-COCO datasets show that CAReD significantly improves upon two baseline detectors (+ 3.6% on Pascal VOC benchmark and + 4.4% on MS-COCO benchmark), achieving state-of-the-art results under few-shot detection settings.

Protective Effects of Onjisaponin B in a Mouse Model of Alzheimer’s Disease via Enhancement of Hippocampal Neuroplasticity

Alzheimer’s disease mainly affects elderly population leading to impairment in cogitation. A lack of clear understanding of the mechanism of Alzheimer’s disease has led to a lack of definite therapeutic option. Herein we have explored the effect of Onjisaponin B derived from the traditional Chinese herbal medicinal plant Radix Polygalae in an animal model of Alzheimer’s disease. Onjisaponin B significantly reduced the severity of experimental Alzheimer’s disease in mice measured by learning abilities, spatial learning, memory, and recognition of novel objects via modulation of hippocampal neuroplasticity. Neuroplasticity was further confirmed by silver staining and expression of major proteins in the hippocampal synapse. Furthermore, Onjisaponin B remarkably altered the morphology of neuron dendrites in the CA1 region by increasing the numbers of apical and basal dendrites of neurons, and the length of neurons. In conclusion, Onjisaponin B might modulate neuroplasticity to attenuate Alzheimer’s disease.

Prenatal alcohol-induced sex differences in immune, metabolic and neurobehavioral outcomes in adult rats

Prenatal alcohol exposure (PAE) can result in neurobehavioral anomalies, that may be exacerbated by co-occurring metabolic and immune system deficits. To test the hypothesis that the peripheral inflammation in adult PAE offspring is linked to poor glucose metabolism and neurocognitive deficits, pregnant Sprague-Dawley rats were exposed to ethanol vapor or ambient air during the latter half of gestation. We assessed, in adult offspring of both sexes, performance on a battery of neurocognitive behaviors, glucose tolerance, circulating and splenic immune cells by flow-cytometry, and circulating and tissue (liver, mesenteric adipose, and spleen) cytokines by multiplexed assays. PAE reduced both the ratio of spleen to body weight and splenic regulatory T-cell (Treg) numbers. PAE males, but not females exhibited an increase in circulating monocytes. Overall, PAE males exhibited a suppression of cytokine levels, while PAE females exhibited elevated cytokines in mesenteric adipose tissue (IL-6 and IL1α) and liver (IFN-γ, IL-1β, IL-13, IL-18, IL-12p70, and MCP-1), along with increased glucose intolerance. Behavioral analysis also showed sex-dependent PAE effects. PAE-males exhibited increased anxiety-like behavior while PAE-females showed decreased social interaction. PAE offspring of both sexes exhibited impaired recognition of novel objects. Multilinear regression modeling to predict the association between peripheral immune status, glucose intolerance and behavioral outcomes, showed that in PAE offspring, higher levels of adipose leptin and liver TNF- α predicted higher circulating glucose levels. Lower liver IL-1 α and higher plasma fractalkine predicted more time spent in the center of an open-field with sex being an additional predictor. Higher circulating and splenic Tregs predicted better social interaction in the PAE-offspring. Collectively, our data show that peripheral immune status is a persistent, sex-dependent predictor of glucose intolerance and neurobehavioral function in adult PAE offspring.

A Sensitive Homecage-Based Novel Object Recognition Task for Rodents.

The recognition of novel objects is a common cognitive test for rodents, but current paradigms have limitations, such as low sensitivity, possible odor confounds and stress due to being performed outside of the homecage. We have developed a paradigm that takes place in the homecage and utilizes four stimuli per trial, to increase sensitivity. Odor confounds are eliminated because stimuli consist of inexpensive, machined wooden beads purchased in bulk, so each experimental animal has its own set of stimuli. This paradigm consists of three steps. In Step 1, the sampling phase, animals freely explore familiar objects (FO). Novel Objects (NO1 and NO2) are soiled with bedding from the homecage, to acquire odor cues identical to those of the FO. Steps 2 and 3 are test phases. Herein we report results of this paradigm from neurologically intact adult rats and mice of both sexes. Identical procedures were used for both species, except that the stimuli used for the mice were smaller. As expected in Step 2 (NO1 test phase), male and female rats and mice explored NO1 significantly more than FO. In Step 3 (NO2 test phase), rats of both sexes demonstrated a preference for NO2, while this was seen only in female mice. These results indicate robust novelty recognition during Steps 2 and 3 in rats. In mice, this was reliably seen only in Step 2, indicating that Step 3 was difficult for them under the given parameters. This paradigm provides flexibility in that length of the sampling phase, and the delay between test and sampling phases can be adjusted, to tailor task difficulty to the model being tested. In sum, this novel object recognition test is simple to perform, requires no expensive supplies or equipment, is conducted in the homecage (reducing stress), eliminates odor confounds, utilizes 4 stimuli to increase sensitivity, can be performed in both rats and mice, and is highly flexible, as sampling phase and the delay between steps can be adjusted to tailor task difficulty. Collectively, these results indicate that this paradigm can be used to quantify novel object recognition across sex and species.

A general-purpose mechanism of visual feature association in visual word identification and beyond

As writing systems are a relatively novel invention (slightly over 5 kya),1 they could not have influenced the evolution of our species. Instead, reading might recycle evolutionary older mechanisms that originally supported other tasks2,3 and preceded the emergence of written language. Accordingly, it has been shown that baboons and pigeons can be trained to distinguish words from nonwords based on orthographic regularities in letter co-occurrence.4,5 This suggests that part of what is usually considered reading-specific processing could be performed by domain-general visual mechanisms. Here, we tested this hypothesis in humans: if the reading system relies on domain-general visual mechanisms, some of the effects that are often found with orthographic material should also be observable with non-orthographic visual stimuli. We performed three experiments using the same exact design but with visual stimuli that progressively departed from orthographic material. Subjects were passively familiarized with a set of composite visual items and tested in an oddball paradigm for their ability to detect novel stimuli. Participants showed robust sensitivity to the co-occurrence of features ("bigram" coding) with strings of letter-like symbols but also with made-up 3D objects and sinusoidal gratings. This suggests that the processing mechanisms involved in the visual recognition of novel words also support the recognition of other novel visual objects. These mechanisms would allow the visual system to capture statistical regularities in the visual environment.6-9 We hope that this work will inspire models of reading that, although addressing its unique aspects, place it within the broader context of vision.

Cognitively Impaired Old Mice Display Correlated Reduction in Cortical NMDA Receptor and Complex IV

Cognitive decline in older adults represents a major challenge since cognitive impairment is found in 10% of those ≥ 65 and 50% ≥ 85. Thus it is increasingly important to understand the impact of aging on cognitive health. We performed a battery of tests to assess cognition in 6 month-old (n=12) and 24 month-old (n=8) C57BL/6J mice, equivalent to 30 and 70 year old humans, respectively, and also assessed protein markers in cortex for mitochondrial health and cognition. We found that aged mice displayed fewer spontaneous alternations in the T maze test (p=0.034) and lower recognition of novel objects (p=0.022). In addition, aged mice showed prolonged escape time in the Barnes maze (p=0.035), all of which taken together suggest reduced capacity for learning and recall. Aged mice also exhibited diminished nest building (p<0.001), revealing an impaired functional capacity analogous to the instrumental activities of daily living (IADL) geriatric assessment. We found reduced mitochondrial complex IV expression in the cortices of aged mice concomitant with less expression of N-Methyl D-Aspartate (NMDA) receptor subunits 1, 2A and 2B. The cortices from old mice also exhibited greater expression of immature brain derived neurotrophic factor (pro-BDNF). The alterations in NMDA receptors and pro BDNF are consistent with memory impairment and greater neuronal cell death. Therefore, aged mice exhibit significantly reduced recall and learning ability alongside marked alterations in mitochondrial complex, NMDA receptor, and pro-BDNF expression. Studies are underway to assess whether these molecular changes are responsible for the cognitive declines with aging.

Impairment to Cognitive Functions in Wistar Rats in a Model of the Preclinical Stage of Parkinson’s Disease

The preclinical stage of Parkinson’s disease (PD), when most dopaminergic neurons in the nigrostriatal system of the brain are still intact and compensatory mechanisms have not yet been overwhelmed, is the most effective “therapeutic window.” Much attention in recent years has therefore been focused on seeking early markers for the neurodegenerative process and developing experimental models. The present study addressed the task of analyzing early behavioral changes reflecting impairments in the cognitive and affective domains on modeling the premotor stage of PD in rats, with identification of the most informative tests. A model developed in our laboratory is based on a prolonged (21 days) preclinical stage of PD in rats by increasing suppression of the ubiquitin-proteasome system of the brain induced by two intranasal doses of the specific proteasome inhibitor lactacystin. Cognitive impairments were assessed using the novel object recognition and Y maze tests and the what–where–when paradigm. Anxiety was assessed in the elevated plus maze and open field tests. Administration of lactacystin was found to degrade spatial memory, episodic memory, and recognition of novel objects in rats on the background of a transient increase in the level of anxiety. These data suggest that impairments in the cognitive and affective domains may be early signs of the development of neurodegeneration in the brain.

Scale and translation-invariance for novel objects in human vision

Though the range of invariance in recognition of novel objects is a basic aspect of human vision, its characterization has remained surprisingly elusive. Here we report tolerance to scale and position changes in one-shot learning by measuring recognition accuracy of Korean letters presented in a flash to non-Korean subjects who had no previous experience with Korean letters. We found that humans have significant scale-invariance after only a single exposure to a novel object. The range of translation-invariance is limited, depending on the size and position of presented objects. To understand the underlying brain computation associated with the invariance properties, we compared experimental data with computational modeling results. Our results suggest that to explain invariant recognition of objects by humans, neural network models should explicitly incorporate built-in scale-invariance, by encoding different scale channels as well as eccentricity-dependent representations captured by neurons’ receptive field sizes and sampling density that change with eccentricity. Our psychophysical experiments and related simulations strongly suggest that the human visual system uses a computational strategy that differs in some key aspects from current deep learning architectures, being more data efficient and relying more critically on eye-movements.

Sex and estrous cycle dependent changes in locomotor activity, anxiety and memory performance in aged mice after exposure of light at night.

Light-at-night (LAN) can affect mammalian behaviour. But, the effects of LAN on aged rodents remain undefined yet. In the present investigation, aged Swiss Albino mice, habituated in regular light-dark cycle, were exposed to bright-light-pulse (1-h) at night on the day of study followed by experimentations for assessment of locomotor activities in the open field, anxiety in the elevated plus maze and short-term memory for novel object recognition (NOR) in the habituated field. Under without-bright-light exposure, (a) aged proestrous females showed greater locomotor activities and less anxiety than in aged diestrous females, (b) aged males showed locomotor activities and anxiety level similar to aged diestrous females and aged proestrous females respectively and (c) all animals failed to retain in object discrimination memory. LAN exposure exhibited the continual failure of such retention of memory while animals showed free and spontaneous exploration with thigmotactic behaviour having no object bias and/or phobia, but time stay in objects by animals altered variably among sexes and stages of estrous cycle. Overall, the LAN caused (a) diminution in locomotor activities, rise in anxiety and failure of memory for recognition of both familiar and novel objects in aged proestrous females, (b) hyperlocomotor activities and reduction in anxiety in both males and diestrous females with the failure of memory for recognition of novel objects only in aged males while diestrous females showed enhanced exploration time to both objects during NOR. Thus, nocturnal behaviour of aged mice varies with sex and estrous cycle and light acts differentially on them.

Effects of placental growth factor deficiency on behavior, neuroanatomy, and cerebrovasculature of mice

Preeclampsia, a hypertensive syndrome occurring in 3-5% of human pregnancies, has lifelong health consequences for fetuses. Cognitive ability throughout life is altered, and adult stroke risk is increased. One potential etiological factor for altered brain development is low concentrations of proangiogenic placental growth factor (PGF). Impaired PGF production may promote an antiangiogenic fetal environment during neural and cerebrovascular development. We previously reported delayed vascularization of the hindbrain, altered retinal vascular organization, and less connectivity in the circle of Willis in Pgf-/- mice. We hypothesized Pgf-/- mice would have impaired cognition and altered brain neuroanatomy in addition to compromised cerebrovasculature. Cognitive behavior was assessed in adult Pgf-/- and Pgf+/+ mice by four paradigms followed by postmortem high-resolution MRI of neuroanatomy. X-ray microcomputed tomography imaging investigated the three-dimensional cerebrovascular geometry in another cohort. Pgf-/- mice exhibited poorer spatial memory, less depressive-like behavior, and superior recognition of novel objects. Significantly smaller volumes of 10 structures were detected in the Pgf-/- compared with Pgf+/+ brain. Pgf-/- brain had more total blood vessel segments in the small-diameter range. Lack of PGF altered cognitive functions, brain neuroanatomy, and cerebrovasculature in mice. Pgf-/- mice may be a preclinical model for the offspring effects of low-PGF preeclampsia gestation.

Haptic Zero-Shot Learning: Recognition of objects never touched before

Object recognition is essential to enable robots to interact with their environment. Robots should be capable, on one hand of recognizing previously experienced objects, and on the other, of using the experienced objects for learning novel objects, i.e. objects for which training data are not available. Recognition of such novel objects can be achieved with Zero-Shot Learning (ZSL). In this work, we show the potential of ZSL for haptic recognition. First, we design a zero-shot haptic recognition algorithm and, using the extensive PHAC-2 database (Chu et al., 2015) as well as our own, we adapt, analyze and optimize the ZSL for the challenges and constraints characteristic of haptic recognition. Finally, we apply the optimized algorithm for haptic recognition of daily-life objects using an anthropomorphic robot hand. Our algorithm enables the robot to recognize eight of the ten novel objects handed to it.

Neuroprotective action and mechanistic evaluation of protodioscin against rat model of Parkinson's disease.

Parkinson's disease (PD) is the most widespread motor-affecting disease affecting majorly middle- and late age population. Thus, in the current study, we intended to explore the neuroprotective effect of protodioscin (Proto) against 6-hydroxydopamine (6-OHDA)-induced PD rat model. After induction of PD with the injection of 6-OHDA, the different dose of Proto was administered for the duration of experimental protocol (2 months). We have scrutinized the consequence of Proto on the cognitive behaviours via Moris water maze (MWM), and recognition of novel objects and its location tasks. The effect of Proto was also investigated on the expression of Nrf2 in human neuroblastoma SHSY5Y cells via western blot analysis. The results showed significant decrease in travelled distance as compared by the lesion treated group. Further significant difference was revealed in the latency time to detect the platform that is visible and it confirmed that, there were no noteworthy dissimilarity was observed in the visual and motor function ability. The result also suggests that, the activation of Nrf2 is the possible mechanism of neuroprotection of Proto against PD. As a concluding remark, the present study confirmed the neuroprotective role of Proto against PD both in in vitro and in vivo models.

Neuron-derived insulin-like growth factor (IGF)-I is necessary for normal cognition and hedonic activity of mice

The role of IGF-I and indoleamine-2,3-dioxygenase (IDO)1 in animal behavior is an expanding field, with IGF-I and IDO1 having opposing roles. IGF-I is anti-depressive, whereas IDO1 mediates several depression-like behaviors. The cellular sources, or targets, of IGF-I and IDO1 underpinning these roles remain poorly characterized. Mice with lox-P gene inserts targeting Igf1, Ido1 or type-1-IGF receptor (Igf1r) were bred to mice expressing Cre-recombinase in neurons (Neu-Cre) or myeloid-derived cells (My-Cre) to generate knockdown models. We hypothesized that neuronal IGF-I acts on glial IGF1R’s to modulate behavior and cognition, and central IDO1 is required for depression-like behaviors. Cognition was assessed using object and social discrimination tests (ODT, SDT) to evaluate recognition and exploration of novel objects or mice, respectively. Igf1-Neu-Cre mice did not discriminate novel over familiar objects 1 and 24 h post-training, whereas Igf1r-Neu-Cre and Ido1-Neu-Cre mice performed poorly at 24 h. With My-Cre strains, only Igf1r-My-Cre mice underperformed at 1 h. Knockdown of Igf1, Igf1r or Ido1 did not diminish performance in the SDT or anxiolytic activity (zero-maze open-field activity). Igf1-My-Cre mice took longer to establish a preference for sucrose in the two-bottle preference test of anhedonia, and Igf1-Neu-Cre mice had a prolonged recovery period following peripheral LPS administration. These results suggest neuronal and myeloid-derived IGF-I are necessary for hedonic activity, whereas neuronal IGF-I, IGF1R and IDO1 and myeloid IGF1R support optimal cognitive performance in the ODT.

Recognition memory impairments caused by false recognition of novel objects.

A fundamental assumption underlying most current theories of amnesia is that memory impairments arise because previously studied information either is lost rapidly or is made inaccessible (i.e., the old information appears to be new). Recent studies in rodents have challenged this view, suggesting instead that under conditions of high interference, recognition memory impairments following medial temporal lobe damage arise because novel information appears as though it has been previously seen. Here, we developed a new object recognition memory paradigm that distinguished whether object recognition memory impairments were driven by previously viewed objects being treated as if they were novel or by novel objects falsely recognized as though they were previously seen. In this indirect, eyetracking-based passive viewing task, older adults at risk for mild cognitive impairment showed false recognition to high-interference novel items (with a significant degree of feature overlap with previously studied items) but normal novelty responses to low-interference novel items (with a lower degree of feature overlap). The indirect nature of the task minimized the effects of response bias and other memory-based decision processes, suggesting that these factors cannot solely account for false recognition. These findings support the counterintuitive notion that recognition memory impairments in this memory-impaired population are not characterized by forgetting but rather are driven by the failure to differentiate perceptually similar objects, leading to the false recognition of novel objects as having been seen before.

Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum

The importance of cholinergic neurons projecting from the medial septum (MS) of the basal forebrain to the hippocampus in memory function has been controversial. The aim of this study was to determine whether loss of cholinergic neurons in the MS disrupts object and/or object location recognition in male Sprague-Dawley rats. Animals received intraseptal injections of either vehicle, or the selective cholinergic immunotoxin 192 IgG-saporin (SAP). 14 days later, rats were tested for novel object recognition (NOR). Twenty-four hours later, these same rats were tested for object location recognition (OLR) (recognition of a familiar object moved to a novel location). Intraseptal injections of SAP produced an 86% decrease in choline acetyltransferase (ChAT) activity in the hippocampus, and a 31% decrease in ChAT activity in the frontal cortex. SAP lesion had no significant effect on NOR, but produced a significant impairment in OLR in these same rats. The results support a role for septo-hippocampal cholinergic projections in memory for the location of objects, but not for novel object recognition.

Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions

Identifying genes involved in social behavior is important for autism research. Williams-Beuren syndrome (WBS) is a developmental syndrome with unique neurocognitive features, including low IQ, deficits in visuospatial and visual-motor abilities, hypersensitivity to sounds, hypersociability, and increased general anxiety. The syndrome is caused by a recurrent hemizygous deletion of the 7q11.23 region, containing about 28 genes. One of genes in the region, GTF2I, has been implicated in the hypersociability and visuospatial deficits of WBS based on genotype-phenotype correlation studies of patients with atypical deletions. In order to clarify the involvement of GTF2I in neurocognitive function, especially social behavior, we have developed and characterized Gtf2i-deficient mice. We found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports. Gtf2i heterozygous animals show no gross changes in brain structure or development. Furthermore, heterozygous animals show no alterations in learning and memory, including spatial memory as assessed by the Morris water maze, but show alterations in the recognition of novel objects. Interestingly, they show increased social interaction with unfamiliar mice and do not show typical social habituation processes, reminiscent of the hypersociability observed in WBS patients. The mice do not appear to show increased anxiety, supporting a specific effect of Gtf2i on defined domains of the WBS phenotype. These data indicate that Gtf2i is involved in several aspects of embryonic development and the development of social neurocircuitry and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients.

The effects of temporal delay and orientation on haptic object recognition

We examined the effects of interstimulus interval (ISI) and orientation changes on the haptic recognition of novel objects, using a sequential shape-matching task. The stimuli consisted of 36 wedge-shaped plastic objects that varied along two shape dimensions (hole/bump and dip/ridge). Two objects were presented at either the same orientation or a different orientation, separated by either a short (3-sec) ISI or a long (15-sec) ISI. In separate conditions, ISI was blocked or randomly intermixed. Participants ignored orientation changes and matched on shape alone. Although performance was better in the mixed condition, there were no other differences between conditions. There was no decline in performance at the long ISI. There were similar, marginally significant benefits to same-orientation matching for short and long ISIs. The results suggest that the perceptual object representations activated from haptic inputs are both stable, being maintained for at least 15 sec, and orientation sensitive.