scholarly journals A New Paradigm for Training Hyperactive Dopamine Transporter Knockout Rats: Influence of Novel Stimuli on Object Recognition

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia P. Kurzina ◽  
Anna B. Volnova ◽  
Irina Y. Aristova ◽  
Raul R. Gainetdinov

Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Pi-Kai Chang ◽  
Jung Chu ◽  
Ya-Ting Tsai ◽  
Yan-Heng Lai ◽  
Jin-Chung Chen

Abstract Background Over-stimulation of dopamine signaling is thought to underlie the pathophysiology of a list of mental disorders, such as psychosis, mania and attention-deficit/hyperactivity disorder. These disorders are frequently associated with cognitive deficits in attention or learning and memory, suggesting that persistent activation of dopamine signaling may change neural plasticity to induce cognitive or emotional malfunction. Methods Dopamine transporter knockdown (DAT-KD) mice were used to mimic a hyper-dopamine state. Novel object recognition (NOR) task was performed to assess the recognition memory. To test the role of dopamine D3 receptor (D3R) on NOR, DAT-KD mice were treated with either a D3R antagonist, FAUC365 or by deletion of D3R. Total or phospho-GSK3 and –ERK1/2 signals in various brain regions were measured by Western blot analyses. To examine the impact of GSK3 signal on NOR, wild-type mice were systemically treated with GSK3 inhibitor SB216763 or, micro-injected with lentiviral shRNA of GSK3β or GSK3α in the medial prefrontal cortex (mPFC). Results We confirmed our previous findings that DAT-KD mice displayed a deficit in NOR memory, which could be prevented by deletion of D3R or exposure to FAUC365. In WT mice, p-GSK3α and p-GSK3β were significantly decreased in the mPFC after exposure to novel objects; however, the DAT-KD mice exhibited no such change in mPFC p-GSK3α/β levels. DAT-KD mice treated with FAUC365 or with D3R deletion exhibited restored novelty-induced GSK3 dephosphorylation in the mPFC. Moreover, inhibition of GSK3 in WT mice diminished NOR performance and impaired recognition memory. Lentiviral shRNA knockdown of GSK3β, but not GSK3α, in the mPFC of WT mice also impaired NOR. Conclusion These findings suggest that D3R acts via GSK3β signaling in the mPFC to play a functional role in NOR memory. In addition, treatment with D3R antagonists may be a reasonable approach for ameliorating cognitive impairments or episodic memory deficits in bipolar disorder patients.


2018 ◽  
Author(s):  
Iasmina Hornoiu ◽  
John Gigg ◽  
Deborah Talmi

AbstractThe allocation of attention can be modulated by the emotional value of a stimulus. In order to understand the biasing influence of emotion on attention allocation further, we require an animal test of how motivational salience modulates attention. In mice, female odour triggers arousal and elicits emotional responses in males. Here, we determined the extent to which objects labelled with female odour modulated the attention of C57BL/6J male mice. Seven experiments were conducted, using a modified version of the spontaneous Novel Object Recognition task. Attention was operationalised as differential exploration time of identical objects that were labelled with either female mouse odour (O+), a non-social odour, almond odour (Oa) or not labelled with any odour (O-). In some experiments we tested trial unique (novel) objects than never carried an odour (X-). We found that when single objects were presented, as well as when two objects were presented simultaneously (so competed with each other for attention), O+ received preferential attention compared to O-. This result was independent of whether O+ was at a novel or familiar location. When compared with Oa at a novel location, O+ at a familiar location attracted more attention. Compared to X-, O+ received more exploration only when placed at a novel location, but attention to O+ and X- was equivalent when they were placed in a familiar location. These results suggest that C57BL/6J male mice weigh up aspects of odour, object novelty and special novelty for motivational salience, and that, in some instances, female odour elicits more attention (object exploration) compared to other olfactory stimuli and visual object novelty. The findings of this study pave the way to using motivationally-significant odours to modulate the cognitive processes that give rise to novel object recognition.


2021 ◽  
Vol 15 ◽  
Author(s):  
Jessica I. Wooden ◽  
Michael J. Spinetta ◽  
Teresa Nguyen ◽  
Charles I. O’Leary ◽  
J. Leigh Leasure

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoxing Mei ◽  
Mofen Cen ◽  
Xu Luo ◽  
Shiming Qiu ◽  
Yun Pan

Prolonged exposure to an oriented stimulus causes a subsequent test stimulus to be perceived as tilted in the opposite direction, a phenomenon referred to as the tilt aftereffect (TAE). Previous studies have demonstrated that high-level cognitive functions such as attention can modulate the TAE, which is generally well-known as a low-level perceptual process. However, it is unclear whether working memory load, another high-level cognitive function, could modulate the TAE. To address this issue, here we developed a new paradigm by combining a working memory load task with a TAE task. Participants firstly remembered a stream of digits (Experiment 1) or four color-shape conjunctions (Experiment 2) under high/low load conditions, and then recognized the probe stimuli (digits or a color-shape conjunction), which were presented at the center of an adapting grating. After the recognition task (i.e., the adaptation stage), participants performed an orientation judgment task to measure their TAEs. The result of Experiment 1, where the load stimuli were digits, showed that the magnitude of the TAEs were reduced under the condition of the high working memory load compared to that of the low working memory load. However, we failed to replicate the finding in Experiment 2, where the load stimuli were color-shape conjunctions. Together, our two experiments provided mixed evidence regarding the working memory load effects on the TAE and further replications are needed in future work.


2020 ◽  
Author(s):  
Joshua S. Rule ◽  
Maximilian Riesenhuber

AbstractHumans quickly learn new visual concepts from sparse data, sometimes just a single example. Decades of prior work have established the hierarchical organization of the ventral visual stream as key to this ability. Computational work has shown that networks which hierarchically pool afferents across scales and positions can achieve human-like object recognition performance and predict human neural activity. Prior computational work has also reused previously acquired features to efficiently learn novel recognition tasks. These approaches, however, require magnitudes of order more examples than human learners and only reuse intermediate features at the object level or below. None has attempted to reuse extremely high-level visual features capturing entire visual concepts. We used a benchmark deep learning model of object recognition to show that leveraging prior learning at the concept level leads to vastly improved abilities to learn from few examples. These results suggest computational techniques for learning even more efficiently as well as neuroscientific experiments to better understand how the brain learns from sparse data. Most importantly, however, the model architecture provides a biologically plausible way to learn new visual concepts from a small number of examples, and makes several novel predictions regarding the neural bases of concept representations in the brain.Author summaryWe are motivated by the observation that people regularly learn new visual concepts from as little as one or two examples, far better than, e.g., current machine vision architectures. To understand the human visual system’s superior visual concept learning abilities, we used an approach inspired by computational models of object recognition which: 1) use deep neural networks to achieve human-like performance and predict human brain activity; and 2) reuse previous learning to efficiently master new visual concepts. These models, however, require many times more examples than human learners and, critically, reuse only low-level and intermediate information. None has attempted to reuse extremely high-level visual features (i.e., entire visual concepts). We used a neural network model of object recognition to show that reusing concept-level features leads to vastly improved abilities to learn from few examples. Our findings suggest techniques for future software models that could learn even more efficiently, as well as neuroscience experiments to better understand how people learn so quickly. Most importantly, however, our model provides a biologically plausible way to learn new visual concepts from a small number of examples.


2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Ying-Chen Yang ◽  
Chia-Nan Chen ◽  
Carol-Imei Wu ◽  
Wei-Jan Huang ◽  
Tsun-Yung Kuo ◽  
...  

NBM-T-L-BMX-OS01 (BMX) was derived from the semisynthesis of osthole, isolated fromCnidium monnieri(L.) Cuss., and was identified to be a potent inhibitor of HDAC8. This study shows that HDAC8 is highly expressed in the pancreas and the brain. The function of HDAC8 in the brain has not been adequately studied. Because BMX enhances neurite outgrowth and cAMP response element-binding protein (CREB) activation, the effect of BMX on neural plasticity such as learning and memory is examined. To examine declarative and nondeclarative memory, a water maze, a passive one-way avoidance task, and a novel object recognition task were performed. Results from the water maze revealed that BMX and suberoylanilide-hydroxamic-acid-(SAHA-) treated rats showed shorter escape latency in finding the hidden platform. The BMX-treated animals spent more time in the target quadrant in the probe trial performance. An analysis of the passive one-way avoidance results showed that the BMX-treated animals stayed longer in the illuminated chamber by 1 day and 7 days after footshock. The novel object recognition task revealed that the BMX-treated animals showed a marked increase in the time spent exploring novel objects. Furthermore, BMX ameliorates scopolamine-(Sco-) induced learning and memory impairment in animals, indicating a novel role of BMX in learning and memory.


Author(s):  
István Winkler ◽  
Nelson Cowan

Abstract. Everyday experience tells us that some types of auditory sensory information are retained for long periods of time. For example, we are able to recognize friends by their voice alone or identify the source of familiar noises even years after we last heard the sounds. It is thus somewhat surprising that the results of most studies of auditory sensory memory show that acoustic details, such as the pitch of a tone, fade from memory in ca. 10-15 s. One should, therefore, ask (1) what types of acoustic information can be retained for a longer term, (2) what circumstances allow or help the formation of durable memory records for acoustic details, and (3) how such memory records can be accessed. The present review discusses the results of experiments that used a model of auditory recognition, the auditory memory reactivation paradigm. Results obtained with this paradigm suggest that the brain stores features of individual sounds embedded within representations of acoustic regularities that have been detected for the sound patterns and sequences in which the sounds appeared. Thus, sounds closely linked with their auditory context are more likely to be remembered. The representations of acoustic regularities are automatically activated by matching sounds, enabling object recognition.


2020 ◽  
Vol 7 (9) ◽  
pp. 200988
Author(s):  
Regan Fry ◽  
Jeremy Wilmer ◽  
Isabella Xie ◽  
Mieke Verfaellie ◽  
Joseph DeGutis

The issue of the face specificity of recognition deficits in developmental prosopagnosia (DP) is fundamental to the organization of high-level visual memory and has been increasingly debated in recent years. Previous DP investigations have found some evidence of object recognition impairments, but have almost exclusively used familiar objects (e.g. cars), where performance may depend on acquired object-specific experience and related visual expertise. An object recognition test not influenced by experience could provide a better, less contaminated measure of DPs' object recognition abilities. To investigate this, in the current study we tested 30 DPs and 30 matched controls on a novel object memory test (NOMT Ziggerins) and the Cambridge Face Memory Test (CFMT). DPs with severe impairment on the CFMT showed no differences in accuracy or reaction times compared with controls on the NOMT. We found similar results when comparing DPs with a larger sample of 274 web-based controls. Additional individual analyses demonstrated that the rate of object recognition impairment in DPs did not differ from the rate of impairment in either control group. Together, these results demonstrate unimpaired object recognition in DPs for a class of novel objects that serves as a powerful index for broader novel object recognition capacity.


GeroPsych ◽  
2010 ◽  
Vol 23 (3) ◽  
pp. 169-175 ◽  
Author(s):  
Adrian Schwaninger ◽  
Diana Hardmeier ◽  
Judith Riegelnig ◽  
Mike Martin

In recent years, research on cognitive aging increasingly has focused on the cognitive development across middle adulthood. However, little is still known about the long-term effects of intensive job-specific training of fluid intellectual abilities. In this study we examined the effects of age- and job-specific practice of cognitive abilities on detection performance in airport security x-ray screening. In Experiment 1 (N = 308; 24–65 years), we examined performance in the X-ray Object Recognition Test (ORT), a speeded visual object recognition task in which participants have to find dangerous items in x-ray images of passenger bags; and in Experiment 2 (N = 155; 20–61 years) in an on-the-job object recognition test frequently used in baggage screening. Results from both experiments show high performance in older adults and significant negative age correlations that cannot be overcome by more years of job-specific experience. We discuss the implications of our findings for theories of lifespan cognitive development and training concepts.


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