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1

The role of dopamine transporter in attentional functions

100%
Cybulska-Klosowicz A.
Acta Neurobiologiae Experimentalis
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2014
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tom 74
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nr 3
Attentional functions are regulated by a dopaminergic (DA) system. Dopamine transporter (DAT), regulating DA neurotransmission, likely plays a role in controlling the influence of DA in cognitive processes. The aim of the study was to examine the role of DAT in attention. Mice with DAT gene genetically deleted (DAT+/- heterozygotes) were compared with the wild type (WT) mice in several tests of attention. Locomotor activity and non-selective attention were tested in a Làt-maze. Attentional set-shifting was tested in intradimensional shift (IDS) and in extradimensional shift (EDS) phases of the attentional set-shifting task (ASST). Associative and reversal learning were tested in a simple discrimination (SD), compound discrimination (CD) and reversal (Rev) phases of ASST task. Sustained attention was tested in an operant chamber. DAT level in the striatum of mice was compared using DAT immunohistochemistry. Neuronal activity during ASST was visualised with the egr-1 and egr-2 immunohistochemistry. The results obtained show that DAT+/- mice have significantly higher scores of locomotor activity in comparison with WT mice. DAT+/- mice do not differ in simple associative learning and non-selective attention scores when compared with WT mice. However, they are impaired in tests that tax executive control function of attention. The results suggest that normal DAT activity level is required for optimal attentional functioning. NSC Grant 2011/01/D/NZ4/04958.
2

Behavioral verification of associative learning in whiskers-related fear conditioning in mice

100%
Cybulska-Klosowicz A.
Acta Neurobiologiae Experimentalis
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2016
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tom 76
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nr 2
Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most Pavlovian conditioning paradigms an auditory stimulus is used as the conditioned stimulus (CS), but conditioning to a tactile CS can also be accomplished. The whisker-to-barrel tactile system in mice offers a convenient way to investigate the brain pathways and mechanisms of learning and plasticity of the cerebral cortex. To support the claim that an animal learns during conditioning sessions and that the resulting plastic changes are associative in nature, objective measures of behavior are necessary. Multiple types of conditioned responses can develop depending on the training situation, CS and unconditioned stimulus (UCS) characteristics. These include physiological responses such as salivation, heart rate, and galvanic skin reaction, and also behavioral responses such as startle reflex potentiation or suppression of an ongoing behavior. When studying learning with the whisker system in behaving mice, stimulation of individual whiskers in a well-controlled manner may require animal restraint, which has the disadvantage of limiting the observation of potential behavioral responses. Stimulation of whiskers in a neck-restraining apparatus evokes head movements. When whisker stimulation (CS) is paired with an aversive UCS during conditioning, the number of head movements decrease in the course of the training. This reaction, called minifreezing, resembles the frequently used behavioral measure known as the freezing response. However, this is only applicable for freely moving animals. This article will review experimental evidence confirming that minifreezing is a relevant index of association formation between the neutral CS and aversive UCS.
3

Deficits in attentional functions and dopamine transporter polymorphisms

63%
Cybulska-Klosowicz A., Giertuga K.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
Attention, its executive function in particular, is regulated by the dopaminergic (DA) system. Dopamine transporter (DAT), regulating DA neurotransmission, likely plays a role in controlling the influence of DA in cognitive processes. We examined the role of DAT in attention in mice and humans. Mice with DAT gene genetically deleted (DAT+/- heterozygotes) were compared with the wild type (WT) mice in several tests measuring attention. The effect of DAT inhibition was examined in mice submitted to repeated administration of selective DAT inhibitor – GBR 12909 and tested after 10 days of withdrawal. Locomotor activity and non-selective attention were tested in a Làt-maze, while attentional set-shifting, associative and reversal learning – in Attentional Set-Shifitng task (ASST). DAT level in the striatum was assessed using DAT immunohistochemistry. Neuronal activity in medial prefrontal cortex (mPFC) during ASST was visualized with the egr-1 and egr-2 immunohistochemistry and with [14C]-2-deoxyglucose autoradiography. Results have shown that DAT+/- mice had significantly higher scores of locomotor activity in comparison with WT mice. Heterozygotes did not differ from WT mice in respect of nonselective attention and associative learning measures. However, they were significantly impaired in more demanding tasks that tax the executive control function of attention. Also, neuronal activity level in mPFC of DAT+/- mice was significantly lower when compared with WT mice. These observations correspond well with behavioral results of children with attention deficit hyperactivity disorder (ADHD) examined in Attention Network Test (ANT), Sustained Attention to Response Task (SART) and in Test of Everyday Attention for Children (TEA-Ch) which revealed substantial deficits in executive function of attention. Measures of attention evaluated in attentional tests were analyzed in terms of relation with DAT1 gene polymorphisms. National Science Centre Grant 2011/01/D/NZ4/04958.
4

Brain activity mapping in mice during classical conditioning and roughness discrimination task

63%
Cybulska-Klosowicz A., Kossut M.
Acta Neurobiologiae Experimentalis
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2005
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tom 65
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nr 5
5

Mice can learn roughness discrimination with vibrissae in a jump stand apparatus

63%
Cybulska-Klosowicz A., Kossut M.
Acta Neurobiologiae Experimentalis
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2001
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tom 61
|
nr 1
6

Somatosensory cortex activation during classical conditioning training in mice

51%
Cybulska-Klosowicz A., Zakrzewska R., Kossut M.
Acta Neurobiologiae Experimentalis
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2005
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tom 65
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nr 3
7

C-fos protein expression during classical conditionig involving stimulation of vibrissae in mice

51%
Cybulska-Klosowicz A., Radwanska K., Kossut M.
Acta Neurobiologiae Experimentalis
|
2001
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tom 61
|
nr 3
8

Bioelectrical brain activity and attentional functions in teenagers with ADHD and healthy controls

51%
Giertuga K. A., Bielecki M., Kossut M., Cybulska-Klosowicz A.
Acta Neurobiologiae Experimentalis
|
2013
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tom 73
|
nr Suppl.1
Attention deficit hyperactivity disorder (ADHD) is a common behavioral diagnosis based on the presence of developmentally inappropriate levels of inattentiveness, overactivity and impulsivity. The prevalence for ADHD among children is estimated at about 3–10%, affecting boys 5 times more often than girls. The aim of the study was to investigate the patterns of attentional functions and brain activity measured with electroencephalography (EEG) in a clinical group aged 11–16 compared with healthy, age- and sexmatched controls. We focused on efficiency of alerting, orienting and executive networks assessed using Posner’s Attention Network Test (ANT) paradigm. Further, the EEG recordings were collected while the participants performed the ANT test. The obtained results, including reaction time (RT) values, Event Related Potential (P300) and time-frequency analyses, are discussed within the context of existing theories of ADHD-related deficits. The project was supported by The National Science Centre, grant number: 2011/01/D/NZ4/04958.
9

DAT1 gene, ADHD, and the development of attentional functions

45%
Cybulska-Klosowicz A., Kuc K., Bielecki M., Racicka-Pawlukiewicz E., Czerwinski M. B.
Acta Neurobiologiae Experimentalis
|
2019
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tom 79
|
nr Suppl.1
INTRODUCTION: Neuropharmacological and human clinical studies have suggested that the dopaminergic system of the brain is substantively involved in normal and pathological phenotypes of attention. Dopamine transporter gene (DAT1) was proposed as a candidate gene for Attention‑Deficit/Hyperactivity Disorder (ADHD). AIM(S): To investigate the effect of the DAT1 gene on performance in the several attentional tasks. METHOD(S): ADHD and healthy children and teenagers aged 9 – 16 were evaluated using tests and procedures involving attentional switching, selective and sustained attention (Test of Everyday Attention, TEA-Ch and Sustained Attention to Response Test, SART), and also three attentional networks – alerting, orienting, and executive attention (Attention Network Test, ANT). DAT1 polymorphism analysis was performed by polymerase chain reaction on saliva samples provided by subjects. ADHD children performed significantly worse in comparison to healthy controls in most of the tasks, demonstrating deficits in various attention processes which were persistent within the examined age range. The results showed an effect of improvement in almost all indices of attentional processes with increasing age in both ADHD and control groups. RESULTS: The results revealed a significant main effect of DAT1 genotype for switching, wherein subjects carrying the 9R allele displayed worse performance in comparison to children with 10R/10R and 10R/11R genotypes. A similar effect of genotype was observed for orienting, which was not disturbed in ADHD subjects. No association between ADHD and the DAT1 polymorphism, and no interaction of DAT1 genotype and ADHD diagnosis were found. CONCLUSIONS: DAT1 is associated with attentional switching and orienting. ADHD is associated with deficits in primary functions that are distinct from those associated with the DAT1 gene polymorphism. FINANCIAL SUPPORT: This research was supported by National Science Centre Poland Grants 2011/01/D/ NZ4/04958 and 2015/17/N/HS6/03020.
10

Somatostatin expressing cells in experience - dependent plasticity in the somatosensory cortex of adult mice

45%
Nowak K., Liguz-Lecznar M., Cybulska-Klosowicz A., Zakrzewska R., Kossut M.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr S
Synaptic plasticity in the nervous system is associated with rapid state-dependent changes that require constant adaptation of the balance between excitation and inhibition. Increasing neuronal activity has been shown to stimulate the inhibitory system to preserve the excitation/inhibition homeostasis. Experimental data suggest an increased inhibitory GABA-ergic neurotransmission in brain structures involved in the learning process. Previously we have shown that classical conditioning involving stimulation of a row of facial vibrissae in adult mice results in an increased density of GABAergic interneurones and increased cortical expression of glutamic acid decarboxylase in granular layer of trained row representation. Also, we have found that parvalbumin containing subpopulation was not involved in the observed changes. From numerous subpopulations of GABAergic neurons, somatostatin (SST) containing cells seem to be likely involved in regulation of activity and plasticity of neuronal networks. To test this hypothesis we have used the sensory training protocol that was based on the classical conditioning where tactile stimulation of one row of sensory whiskers (CS) was paired with a tail shock (UCS). The training was continued for 3 consecutive days and lasted 10 min each day (40 trials). Cells expressing SST were assessed using stereology-based counting in both hemispheres in the barrel cortex. We have shown the substantial (22%) increase of SST-containing cells in the trained row representation. The result suggests that somatostatin is involved in learning induced changes of inhibitory cortical network. Supported by grant No. 2486/B/P01/2010/39 (M.K.) N N301 248639.
11

Potential role of dopamine transporter in behavioral flexibility

45%
Cybulska-Klosowicz A., Dabrowska J., Niedzielec S., Zakrzewska R., Rozycka A.
Acta Neurobiologiae Experimentalis
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2017
|
tom 77
|
nr 2
Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set‑Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined. The animals were treated with the inhibitor to elicit a compensatory DAT up‑regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra‑dimensional shift stages was higher in DAT+/− mutant mice than in WT mice. GBR 12909‑treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr‑1, egr‑2) immunohistochemistry. Density of egr‑2 labeled cells in the OFC was lower in mutant mice than in wild‑types during reversal learning and the expression of the egr‑1 was lower in mutant mice in the OFC and DMS during reversal and intra‑dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task‑induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.
12

Developmental changes in resting-state eeg activity in ADHD: A cross sectional study

39%
Giertuga K., Zakrzewska M. Z., Bielecki M., Racicka E., Kossut M., Cybulska-Klosowicz A.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr Suppl.1
INTRODUCTION: Numerous studies indicate that Attention Deficit/Hyperactivity Disorder (ADHD) is related to some developmental trends, as its symptoms change widely over time. There is a disagreement whether ADHD is related to deviations in brain development or to a delay in brain maturation. The model of deviated brain development suggests that the ADHD brain matures in a fundamentally different way, and does not reach normal maturity at any developmental stage. In contrast, the delayed brain maturation model assumes that the ADHD brain indeed matures in a different, delayed way in comparison to healthy age-matched controls, yet eventually reaches proper maturation. AIM(S): We investigated developmental changes in resting‑state EEG activity to find evidence supporting one of the alternative models. METHOD(S): A total number of 141 participants took part in the study: 67 ADHD and 74 healthy controls. We recorded 5 minutes of resting-state EEG. Each participant’s power estimates were averaged across clusters of electrodes and across frequency bands: delta, theta, alpha, and beta. The absolute power of each frequency was analyzed. To test the combined effect of age and ADHD diagnosis on EEG power spectrum, we performed a regression analysis. RESULTS: The results revealed a typical developmental effect of decreasing absolute EEG power with increasing age. Absolute EEG power was found to decrease linearly especially for delta and theta frequencies in both groups. We also observed differences between groups. The ADHD group had significantly lower absolute power in all frequency bands, with the most pronounced difference in lower theta absolute power. CONCLUSIONS: This study revealed that the resting-EEG developmental pattern was similar in ADHD and healthy controls. Even so, the ADHD group had consistently lower absolute EEG power, mostly in the theta frequency band. Our results are in line with deviant brain maturation hypothesis, as ADHD brain activity would not be considered the same as in healthy controls at any age. FINANCIAL SUPPORT: Supported by National Science Center (Poland) grant 2015/17/N/HS6/03020.
13

Behavioral and neural correlates of attention network test in ADHD children and teenagers an event related potential study

39%
Giertugar K. A., Zakrzewska M., Racicka E., Bielecki M., Kossut M., Cybulska-Klosowicz A.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr Supl.
BACKGROUND AND AIMS: Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders affecting approximately 5% of children and teenagers population. ADHD is characterized by developmentally inappropriate levels of inattention, impulsivity and overactivity. The aim of this study was to investigate attentional processes and their electrophysiological correlates in children and teenagers with ADHD diagnosis. METHODS: Fifty ADHD children and teenagers and 50 age-, and sex-matched healthy controls participated in this study. Participants performed Attention Network Test (ANT, Fan et al. 2002) – paradigm combining cue detection (Posner 1980) with flanker-type paradigm (Eriksen and Eriksen 1974). ANT allows for the behavioral assessment of different attention functions – alerting, orienting, and executive functions. During task performance EEG data were collected using 64 channel EGI Geodesic System. Measures of attention evaluated in attentional test were analyzed in terms of relation to EEG recording results. RESULTS: The results obtained on behavioral level revealed significant differences in ANT performance in above mentioned groups. ADHD participants, when compared with healthy controls, were less accurate and had longer reaction times in the condition evaluating executive attention. We have also found different patterns of Event Related Potentials (ERPs) related to ANT performance in these groups. Results of ERPs calculated for parietal electrodes cluster revealed that P300 amplitude was lower in ADHD group in comparison with controls. CONCLUSIONS: The results of EEG recordings suggest worse allocation of attention resources which may result in deficits in behavioral performance, especially in executive function of attention. These results are discussed in context of current views and theories on attentional networks and deficits observed in ADHD patients. National Science Centre Grant 2011/01/D/NZ4/04958.
14

Deficits in learning-dependent cortical plasticity and sensory discrimination learning in presymptomatic Huntington’s disease mice

39%
Cybulska-Klosowicz A., Mazarakis N., Grote H., Van Dellen A., Blakemore C., Hannan A., Kossut M.
Acta Neurobiologiae Experimentalis
|
2003
|
tom 63
|
nr 5
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