Ca2+ influx is usually considered a central trigger of neuronal plasticity, especially in mechanisms related to transmitter release and synaptic modification. However, plasticity may also involve mechanisms that do not require Ca2+ influx into neurons. We tested whether short-term plasticity can occur in the CA1 region of the mouse hippocampus under Ca2+-free conditions. In Ca2+-free artificial cerebrospinal fluid, in which synaptic transmission was not detected, local stimulation evoked a population potential in CA1, and theta-burst stimulation led to short-term depression during the stimulation protocol. This depression included three separable components: depression within bursts, cumulative depression of the first response across bursts, and enhancement of within-burst depression during repeated bursts. Whole-cell current-clamp recordings showed that the TBS stimulation protocol also changed action-potential kinetics at the level of individual neurons. These changes were expressed in CA1 pyramidal neurons as a reduction of maximum rise rate and slowing of repolarization, whereas stratum oriens interneurons did not show within-burst depression nor enhancement. Together, these data show that theta-burst stimulation can induce Ca2+-influx-independent short-term plasticity of action potentials in hippocampal CA1 pyramidal cells.

Parkinson’s disease is the second most common neurodegenerative movement disorder caused by the death of dopaminergic neurons in the Substantia nigra. The motor symptoms of Parkinson’s disease only become apparent in the late stages, whereas non-motor impairments often manifest earlier. Therefore, devising adequate experimental models to study the pathogenesis of Parkinson’s disease is of fundamental scientific importance. In this study, we aimed to evaluate the behavioral and neurochemical characteristics in a model of the premotor stage of parkinsonism in mice induced by chronic administration of a low dose of methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP. Administering 3 mg/kg of the toxin for 35 days does not cause motor deficits, except in fine motor skills, and results in impaired spatial learning. In addition, this stage is characterized by the depletion of striatum and prefrontal cortex dopamine, decreased tyrosine hydroxylase in striatum and Substantia nigra, increased cytochrome oxidase and superoxide dismutase expression, and microglia activation. Concluding, the presented model made it possible to identify a complex of physiological and neurochemical disorders characteristic of the early stage of Parkinsonism.

The state of interest as a positive emotion is associated with the ability to comprehend new information and/or to better consolidate already perceived information, to increase the attention level to the object, to increase informational processing, and also to influence such processes as learning and motivation. The aim of this study was to reveal oculomotor correlates that can predict the locus of interest in cases of people perceiving educational information from different areas of knowledge presented as text or multimedia content. Sixty (60) volunteers participated in the study (50% males, mean age 22.20 ± 0.51). The stimuli consisted of 16 texts covering a wide range of topics, each accompanied by a comprehension question and an interest assessment questionnaire. It was found that the multimedia content type triggered more visual attention and gave an advantage in the early stages of information processing. The first fixation duration metric for the multimedia stimuli allowed u to characterize the subjective interest assessment. Overall, the results suggest the potential role of eye-tracking in evaluating educational content and it emphasizes the importance of developing solutions based on this method to enhance the effectiveness of the educational process.

Intellectual disability and autistic features are associated with chromosome region 2q23.q23.2 duplication carrying LYPD6 and LYPD6B genes. Here, we analyzed LYPD6 and LYPD6B expression in patients with different neuropsychiatric disorders. Increased LYPD6 and LYPD6B expression was revealed in autism and other disorders. To study possible consequences of Lypd6 and Lypd6b overexpression in the brain, we used a mouse model with intracerebroventricular delivery of recombinant analogs of these proteins. A two-week infusion evoked significant memory impairment and acute stress. Both modulators downregulated hippocampal and amygdala dendritic spine density. No changes in synaptic plasticity were observed. Intracerebroventricular administration by both proteins downregulated hippocampal expression of Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor (nAChR). Similar to Lypd6, Lypd6b targeted different nAChR subtypes in the brain with preferential inhibition of α7- and α4β2-nAChRs. Thus, increased Lypd6 and Lypd6b level in the brain are linked to cholinergic system depression, neuronal atrophy, memory decline, and anxiety.

The behavioral and functional states preceding the onset of specific parkinsonian symptoms were studied at an early (presymptomatic) stage of hemi-parkinsonian syndrome development in rodents and monkeys. The consecutive steps of neuropathological traits development—cognitive impairments developing from weeks 1–2 of rotenone exposure, minor motor impairments on weeks 3–4 before the development of pronounced motor dysfunction, and some biochemical indicators—were studied using the model of hemi-parkinsonian syndrome in rodents induced by chronic administration of low doses of rotenone toxin. The characteristics of visually guided saccades (VGS) while an instrumental conditioning task performing were studied using the model of hemi-parkinsonian syndrome in nonhuman primates (Macaca mulatta) chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin. As MPTP syndrome progresses, an increase in the latencies of VGS and a decline in their accuracy with the retention of an instrumental conditioning performance have been shown. The negative behavioral effects in rodents and primates and biochemical effects in rodents manifested at the presymptomatic stage of the disease, suggest to consider them as early markers of a hemi-parkinsonian syndrome.

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9–17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = − 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology.

Introduction. Cardiac glycosides are natural ligands of Na+/K+-ATPase, which regulate its activity and signaling. Intracerebroventricular administration of ouabain has been previously shown to induce hyperlocomotion in C57Bl/6 mice via a decrease in the rate of dopamine reuptake from the synaptic cleft. Materials and methods. This study involved forty C57BL/6 mice. 1.5 μL of 50 μM ouabain was administered daily into the left lateral cerebral ventricle over the course of 4 days. On day 5, open field, beam balance, and ladder rung walking tests were performed to assess the locomotor activity and motor impairments in the mice. We evaluated changes in the activation of signaling cascades, ratios of proapoptotic and antiapoptotic proteins, and the amount of α1 and α3 isoforms of the Na+/K+-ATPase α-subunit in brain tissue using Western blotting. Na+/K+-ATPase activity was evaluated in the crude synaptosomal fractions of the brain tissues. Results. We observed hyperlocomotion and stereotypic behavior during the open field test 24 hours after the last injection of ouabain. On day 5, the completion time and the number of errors made in the beam balance and ladder rung walking tests increased in the mice that received ouabain. Akt kinase activity decreased in the striatum, whereas the ratio of proapoptotic and antiapoptotic proteins and the number of Na+/K+-ATPase α-subunits did not change. Na+/K+-ATPase activity increased in the striatum and decreased in the brainstem. Conclusions. Long-term exposure to ouabain causes motor impairments mediated by changes in the activation of signaling cascades in dopaminergic neurons.

Oxidative stress, accompanied by mitochondrial dysfunction, is a key mechanism involved in the pathogenesis of Parkinson's disease (PD). Both carnosine and lipoic acid are potent antioxidants, the applicability of which in therapy is hindered by their limited bioavailability. This study aimed to evaluate the neuroprotective properties of a nanomicellar complex of carnosine and lipoic acid (CLA) in a rotenone-induced rat model of PD. Parkinsonism was induced via the administration of 2 mg/kg rotenone over the course of 18 days. Two doses of intraperitoneal CLA (25 mg/kg and 50 mg/kg) were administered alongside rotenone to assess its neuroprotective effect. At 25 mg/kg CLA decreased muscle rigidity and partially restored locomotor activity in animals that received rotenone. Furthermore, it caused an overall increase in brain tissue antioxidant activity, accompanied by a 19% increase in neuron density in the substantia nigra and increased dopamine levels in the striatum relative to animals that only received rotenone. Based on the acquired results, it may be concluded that CLA have neuroprotective properties and could potentially be beneficial in PD treatment when used in conjunction with the base therapy.

During long-term space missions, galactic cosmic rays lead to the risk of radiation-induced early damage to central nervous system and ensuing decline of astronaut operator activity. The visuomotor conditioned task performance was studied in three monkeys ( Macaca mulatta ). This task required the monkeys to execute the visually guided saccades and manual reactions. Two animals were exposed to single cranial proton irradiation (170 MeV, 3 Gy), the third animal was exposed to single proton irradiation of the parietal cortex in Bragg peak (155 MeV, 3 Gy). In course of 3 month after exposure to protons, conditioned task performance was improving in all animals. Saccade and manual responses latencies increased in 20–30 days after irradiation, remaining lengthened for the next 2 month. Parietal cortex irradiation caused greater effect on saccade and manual responses latencies. The obtained results show systemic instrumental conditioning mechanisms to be stable to proton irradiation. However, the functioning of visuomotor integration and executive control systems might be affected, resulting in increase of saccade and manual responses latencies.

Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

В условиях дальних космических полетов радиационные воздействия галактических космических лучей на организм человека приводят к риску ранних поражений центральной нервной системы и, как следствие, нарушениям операторской деятельности космонавтов. У трех обезьян Macaca mulatta исследовано выполнение зрительно-моторной инструментальной условнорефлекторной задачи, включающей зрительно-вызванные саккады и мануальные реакции. Двух обезьян подвергли однократному краниальному облучению протонами (170 МэВ, 3 Гр), у третьей - однократно облучали протонами (155 МэВ, 3 Гр) теменную кору. В течение трех месяцев после облучения инструментальный рефлекс упрочивался у всех обезьян. Через 20-30 суток после облучения у всех обезьян увеличивались латентные периоды саккад и мануальных инструментальных реакций, которые высоко коррелировали. Такие эффекты сохранялись в последующие два месяца. Облучение теменной коры оказывало более выраженные эффекты на латентные периоды саккад и мануальных реакций. Полученные результаты свидетельствуют об устойчивости системных механизмов условнорефлекторной деятельности к радиационному воздействию протонами. Однако при этом возможны нарушения функционирования систем внимания и исполнительного контроля, что отразилось на временных характеристиках движений глаз и рук.

Background: Eye movement parameters are often used during cognitive functioning assessments of patients with psychotic spectrum disorders. It is interesting to compare these oculomotor parameters with cognitive functions, as assessed using psychometric cognitive tests. A network analysis is preferable for understanding complex systems; therefore, the aim of this study was to determine the multidimensional relationships that exist between oculomotor reactions and neurocognition in patients with schizophrenia spectrum disorders. Materials and Methods: A total of 134 subjects (93 inpatients with schizophrenia spectrum disorders (ICD-10) and 41 healthy volunteers) participated in this study. Psychiatric symptom severity was assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Young Mania Rating Scale. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale, and akathisia was assessed using the Barnes Akathisia Rating Scale. Eye movements were recorded using an eye-tracker SMI RED 500, and cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. The statistical analyses were conducted using Minitab 17 Statistical Software, version 17.2.1. Data visualization and additional analyses were performed in the R 4.0.3 environment, using RStudio V 1.3.1093 software. Results: A network model of neurocognitive and oculomotor functions was constructed for the patients. In the full network (which includes all correlations) the median antisaccade latency value is the central element of the oculomotor domain, and the Symbol Coding test, the Digit Sequencing test, and the Verbal Fluency test are central elements in the neurocognitive domain. Additionally, there were connections between other cognitive and oculomotor functions, except for the antisaccade error latency in the oculomotor domain and the Token Motor Task in the neurocognitive domain. Conclusion: Network analysis provides measurable criteria for the assessment of neurophysiological and neurocognitive abnormalities in patients with schizophrenic spectrum disorders and allows to select key targets for their management and cognitive remediation.

Children who survived cerebellar tumor occur with atactic motor dis-orders. These disorders could be represented in postural, locomotor and oculomotor domains. The gait efficiency depends on visual information acquired from saccadic eye movements. The aim of the study was to establish the relationships between measures of tandem gait and saccades and to verify them by stabilometry and general motor score using Bruininks-Oseretsky Test. We used motion capture system (Optitrack) for gait registration and Arrington eye tracker for saccade detection. 15 patients (9–17 years old) survived cerebellar tumors and stayed in rehabilitation center, participated in the study. We found significant relationships between the parameters of tandem gait and saccades: high percent of hypermetric saccades (saccades which overshoot the target) was strongly associated with high tandem gait variability (r = 0.552). Moreover, the degree of impairment of gait and saccadic parameters significantly related to worse postural disturbances (r = 0.752; r = 0.541) and motor skills (r = −0.673; r = −0.612). Observed findings comprehensively characterize the severity of ataxia and could provide new approach for the diagnosis of CNS lesions.

The cerebellum plays an important role in controlling saccadic eye movements and fixing gaze. Cerebellar lesions produce a variety of impairments to oculomotor behavior and associated psychophysiological processes. Such impairments have significant influences on the effectiveness of rehabilitation measures in patients treated for cerebellar tumors. The aims of the present work were to identify and objectively evaluate the effects of cerebellar dysfunction acquired as a result of tumor treatment on the characteristics of the oculomotor system in pediatric patients for subsequent development of diagnostic criteria and quantitative evaluation of the rehabilitation process. A total of 66 children aged 9–17 years took part in the study, all with tumor treatment-induced cerebellar dysfunction; 54 healthy children of the same age also took part. Three oculomotor tests were performed in which eye movements were recorded by videooculography. We found impairments to holding the gaze on visual objects, significant increases in hypermetric saccades, and difficulty with visual scanning in the patients. These dysfunctions of the oculomotor system inevitably led to impairments to a series of cognitive processes – visual perception, attention, memory, and reading. In addition, the phenomenon of hypermetric saccades should be regarded as a special case of cerebellar ataxia syndrome in the patients. These oculomotor impairments need to be considered for effective rehabilitation measures in this class of patients.

Interest as a positive emotion is closely related to the ability to process new information and/or better consolidate the information which has already been perceived, increase in attention to what one is interested in, and indicators of processing, learning, and motivation [1]. Here we aim to identify oculomotor and electroencephalographic correlates, which could serve as predictors of a locus of interest based on the travel locations perception. Thirty-eight (38) healthy volunteers took part in the study (people aged between 18 and 27, the average age was 22 ± 0.4 years, 14 males and 24 females). Eye movements were registered simultaneously with monopolar EEG using a standard 10/20 system (O1, O2, T3, T4, P3, P4, C3, C4, F3, F4). Participants were watching at the slides describing eight different places of interest in Russia. After seeing each slide, volunteers said whether the information shown to them arouse their interest or not. As each text was shown twice in different forms, statistical analysis, taking into account changes in answers about interest, was conducted. The fixation during the first demonstration was longer in case of interest, and doubts in answers also made the fixation duration longer. Saccade amplitudes showed the opposite trend. The electrical activity in the theta-band in frontal channels increased, compared to resting state in case of interest; however, if a participant said that he or she was not interested, there was an even larger increase. Therefore, eye movement and EEG characteristics reflect a subjective assessment of interest when reading information.

This review addresses approaches to modeling impairments to brain function assessed in adulthood by targeted treatments during the perinatal period. Models of neuromental disorders linked with impairments to the dynamics of brain development are considered, along with models of diseases characteristic of older people. Pharmacological actions on the developing brain have been shown to induce delayed behavioral changes opposite to those induced by the drugs used when given to adult animals (for example, the development of a depressive state after perinatal administration of antidepressants). The history of the creation of such experimental models and their potential pathophysiological mechanisms are discussed. The significance of scientific research of this type for practical healthcare is demonstrated.

We analyzed the subjective time estimation of task duration using EEG during a series of Go/NoGo tasks with varying duration. All series of trials were divided into three groups according to the quartiles of distribution of subjective estimates: (1) overestimation, (2) underestimation, and (3) the “most precise estimation” of the task performance time. The underestimation of task duration was associated with the greatest relative spectral power in the β frequency range (13–30 Hz) as compared to other groups, with interhemispheric asymmetry of relative spectral power of β activity being recorded in parietal electrode positions. The most precise estimation of the task performance time was associated with greater relative spectral power, as compared with the overestimation group, and characterized by interhemispheric asymmetry in the frontal and central electrode positions. Thus, the subjective estimation of the Go/NoGo task series time is reflected in the dynamics of relative spectral power in the β frequency band.

Cerebellum plays a crucial role in control of saccadic eye movements and gaze fixation. The cerebellar impairment leads to various disorders of oculomotor behavior and related psychophysiological processes, which, in turn, may affect the efficiency of rehabilitation process of patients who underwent tumor resection surgery on cerebellum. The purpose of this work was to determine the ways and the extent of influence of surgery-related cerebellar dysfunction on visuomotor system of children. We also intended to develop criteria based on these findings to assess the patient’s rehabilitation progress quantitatively as well as qualitatively. 66 children between 9 and 17 years old with surgery-related cerebellar dysfunction were enrolled in this study. The control group consisted of 54 healthy children of the same age. The subjects were to perform 3 oculomotor tasks while their eye movements were recorded using eye tracking technique. We found that children with cerebellar dysfunction had impaired gaze fixation ability, executed more hypermetric saccades and experienced difficulties with visual scanning. These oculomotor system deficiencies inevitably lead to disturbances of various cognitive processes such as visual perception, attention focusing, memory and reading. Also, hypermetric saccades can be treated as a special case of ataxia usually found in patients with cerebellar dysfunction. We conclude that assessment of oculomotor deficiencies should be used to increase the effectiveness of rehabilitation procedures for patients with cerebellar dysfunction.