The "Twin Peaks" method of automated Spike-Wave detection: A two-step, two-criteria Matlab application.

BACKGROUND: There are many automated spike-wave discharge detectors, but the known weaknesses of otherwise good methods and the varying working conditions of different research groups (mainly the access to hardware and software) invite further exploration into alternative approaches. NEW METHOD: The algorithm combines two criteria, one in the time-domain and one in the frequency-domain, exploiting morphological asymmetry and the presence of harmonics, respectively. The time-domain criterion is additionally adjusted by normal modelling between the first and second iterations. RESULTS: We report specificity, sensitivity and accuracy values for 20 recordings from 17 mature, male WAG/Rij rats. In addition, performance was preliminary tested with different hormones, pharmacological injections and species (mice) in a smaller sample. Accuracy and specificity were consistently above 91 %. The number of automatically detected spike-wave discharges was strongly correlated with the numbers derived from visual inspection. Sensitivity varied more strongly than specificity, but high values were observed in both rats and mice. COMPARISON WITH EXISTING METHODS: The algorithm avoids low-voltage movement artifacts, displays a lower false positive rate than many predecessors and appears to work across species, i.e. while designed initially with data from the WAG/Rij rat, the algorithm can pick up seizure activity in the mouse of considerably lower inter-spike frequency. Weaknesses of the proposed method include a lower sensitivity than several predecessors. CONCLUSION: The algorithm excels in being a selective and flexible (based on e.g. its performance across rats and mice) spike-wave discharge detector. Future work could attempt to increase the sensitivity of this approach.

Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats).

Absence epilepsy is a non-convulsive type of epilepsy characterized by the sudden loss of awareness. It is associated with thalamo-cortical impairment, which may cause neuropsychiatric and neurocognitive problems. Rats with spontaneous absence-like seizures are widely used as in vivo genetic models for absence epilepsy; they display behavioral and cognitive problems similar to epilepsy in humans, such as genetic absence epilepsy rats from Strasbourg (GAERS) and Wistar Albino rats from Rijswijk (WAG/Rij). Depression- and anxiety-like behaviors were apparent in GAERS, but no anxiety and depression-like symptoms were found in WAG/Rij rats. Deficits in executive functions and memory impairment in WAG/Rij rats, i.e., cognitive comorbidities, were linked to the severity of epilepsy. Wistar rats can develop spontaneous seizures in adulthood, so caution is advised when using them as a control epileptic strain. This review discusses challenges in the field, such as putative high emotionality in genetically prone rats, sex differences in the expression of cognitive comorbidities, and predictors of cognitive problems or biomarkers of cognitive comorbidities in absence epilepsy, as well as the concept of "the cognitive thalamus". The current knowledge of behavioral and cognitive comorbidities in drug-naive rats with spontaneous absence epilepsy is beneficial for understanding the pathophysiology of absence epilepsy, and for finding new treatment strategies.

A simple and fast ANN-based method of studying slow-wave sleep microstructure in freely moving rats.

Electroencephalography (EEG) is a common technique for measuring brain activity. Artificial Neuronal Networks (ANNs) can provide valuable insights into the brain dynamics of humans and animals. We built a simple and fast shallow ANN-based solution for sleep recognition in EEGs recorded in freely moving rats. The ANN was constructed using open-source software and truncated to one formula with empirically defined weight coefficients. The optimization of the ANN model's performance (i.e., post-processing) relied on a probability-related approach to sleep microstructure. This approach could be a good way to analyze large datasets. In the current dataset, the slow-wave sleep was recognized with the sensitivity of 0.91 and the specificity of 0.98. The optimal model performance achieved with minimum sleep duration of 80-90 s and sleep interruption of 14-18 s. Our results suggest the following fundamental issues. First, 14-18 s sleep interruptions might be the archetypal micro-arousals in rats. Second, slow-wave sleep in rats might be built up of a set of sleep "building blocks" lasting 80-90 s.

Adrenergic mechanisms of absence status epilepticus.

Absence status epilepticus is a prolonged, generalized absence seizure that lasts more than half an hour. The mechanisms underlying the absence of status epilepticus are still not entirely understood. In this study, the study concentrates on alpha2-adrenergic mechanisms of absence status using the WAG/Rij rat model. In this model, a prolonged spike-wave activity was associated with a specific behavioral state in transition between sedation («alpha2-wakefulness¼)-resembled absence status in human patients. Pharmacological activation of alpha2-adrenoreceptors may target the locus coeruleus (presynaptic alpha2-adrenoreceptors) and the thalamic part of the seizure-generating thalamocortical system (postsynaptic alpha2B-adrenoreceptors). The duration of EEG-behavioral correlates of absence status was not dose-dependent and was predetermined by the intensity of absence seizures at baseline. This model could help scientists better understand the underlying causes of absence status and develop more effective and personalized treatments for each individual.

Astrocytes as a target for therapeutic strategies in epilepsy: current insights.

Astrocytes are specialized non-neuronal glial cells of the central nervous system, contributing to neuronal excitability and synaptic transmission (gliotransmission). Astrocytes play a key roles in epileptogenesis and seizure generation. Epilepsy, as a chronic disorder characterized by neuronal hyperexcitation and hypersynchronization, is accompanied by substantial disturbances of glial cells and impairment of astrocytic functions and neuronal signaling. Anti-seizure drugs that provide symptomatic control of seizures primarily target neural activity. In epileptic patients with inadequate control of seizures with available anti-seizure drugs, novel therapeutic candidates are needed. These candidates should treat epilepsy with anti-epileptogenic and disease-modifying effects. Evidence from human and animal studies shows that astrocytes have value for developing new anti-seizure and anti-epileptogenic drugs. In this review, we present the key functions of astrocytes contributing to neuronal hyperexcitability and synaptic activity following an etiology-based approach. We analyze the role of astrocytes in both development (epileptogenesis) and generation of seizures (ictogenesis). Several promising new strategies that attempted to modify astroglial functions for treating epilepsy are being developed: (1) selective targeting of glia-related molecular mechanisms of glutamate transport; (2) modulation of tonic GABA release from astrocytes; (3) gliotransmission; (4) targeting the astrocytic Kir4.1-BDNF system; (5) astrocytic Na+/K+/ATPase activity; (6) targeting DNA hypo- or hypermethylation of candidate genes in astrocytes; (7) targeting astrocytic gap junction regulators; (8) targeting astrocytic adenosine kinase (the major adenosine-metabolizing enzyme); and (9) targeting microglia-astrocyte communication and inflammatory pathways. Novel disease-modifying therapeutic strategies have now been developed, such as astroglia-targeted gene therapy with a broad spectrum of genetic constructs to target astroglial cells.

Alpha2 Adrenergic Modulation of Spike-Wave Epilepsy: Experimental Study of Pro-Epileptic and Sedative Effects of Dexmedetomidine.

In the present report, we evaluated adrenergic mechanisms of generalized spike-wave epileptic discharges (SWDs), which are the encephalographic hallmarks of idiopathic generalized epilepsies. SWDs link to a hyper-synchronization in the thalamocortical neuronal activity. We unclosed some alpha2-adrenergic mechanisms of sedation and provocation of SWDs in rats with spontaneous spike-wave epilepsy (WAG/Rij and Wistar) and in control non-epileptic rats (NEW) of both sexes. Dexmedetomidine (Dex) was a highly selective alpha-2 agonist (0.003-0.049 mg/kg, i.p.). Injections of Dex did not elicit de novo SWDs in non-epileptic rats. Dex can be used to disclose the latent form of spike-wave epilepsy. Subjects with long-lasting SWDs at baseline were at high risk of absence status after activation of alpha2- adrenergic receptors. We create the concept of alpha1- and alpha2-ARs regulation of SWDs via modulation of thalamocortical network activity. Dex induced the specific abnormal state favorable for SWDs-"alpha2 wakefulness". Dex is regularly used in clinical practice. EEG examination in patients using low doses of Dex might help to diagnose the latent forms of absence epilepsy (or pathology of cortico-thalamo-cortical circuitry).

Sex Differences in Behavior and Learning Abilities in Adult Rats.

Laboratory rats have excellent learning abilities and are often used in cognitive neuroscience research. The majority of rat studies are conducted on males, whereas females are usually overlooked. Here, we examined sex differences in behavior and tactile sensitivity in littermates during adulthood (5.8-7.6 months of age). We used a battery of behavioral tests, including the 2% sucrose preference test (positive motivation), a free-choice paradigm (T-maze, neutral situation), and associative fear-avoidance learning (negative motivation, aversive situation). Tactile perception was examined using the von Frey test (aversive situation). In two aversive situations (von Frey test and avoidance learning), females were examined during the diestrus stage of the estrous cycle, and ultrasonic vocalization was recorded in both sexes. It was found that (1) females, but not males, lost their body weight on the first day of the sucrose preference test, suggesting sex differences in their reaction to environmental novelty or in metabolic homeostasis; (2) the tactile threshold in females was lower than in males, and females less frequently emitted aversive ultrasonic calls; (3) in the avoidance learning task, around 26% of males (but no females) were not able to learn and experienced frizzing. Overall, the performance of associative fear-avoidance in males was worse than in females. In general, females demonstrated higher abilities of associative learning and less persistently emitted aversive ultrasonic calls.

Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy.

Spike-wave discharges are the hallmark of idiopathic generalized epilepsy. They are caused by a disorder in the thalamocortical network. Commercially available anti-epileptic drugs have pronounced side effects (i.e., sedation and gastroenterological concerns), which might result from a low selectivity to molecular targets. We suggest a specific subtype of adrenergic receptors (ARs) as a promising anti-epileptic molecular target. In rats with a predisposition to absence epilepsy, alpha2 ARs agonists provoke sedation and enhance spike-wave activity during transitions from awake/sedation. A number of studies together with our own observations bring evidence that the sedative and proepileptic effects require different alpha2 ARs subtypes activation. Here we introduce a new concept on target pharmacotherapy of absence epilepsy via alpha2B ARs which are presented almost exclusively in the thalamus. We discuss HCN and calcium channels as the most relevant cellular targets of alpha2 ARs involved in spike-wave activity generation.

Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy.

In temporal lobe epilepsy, high frequency oscillations serve as electroencephalographic (EEG) markers of epileptic hippocampal tissue. In contrast, absence epilepsy and other idiopathic epilepsies are known to result from thalamo-cortical abnormalities, with the hippocampus involvement considered to be only indirect. We aimed to uncover the role of the hippocampus in absence epilepsy using a genetic rat model of absence epilepsy (WAG/Rij rats), in which spike-wave discharges (SWDs) appear spontaneously in cortical EEG. We performed simultaneous recordings of local field potential from the hippocampal dentate gyrus using pairs of depth electrodes and epidural cortical EEG in freely moving rats. Hippocampal ripples (100-200 Hz) and high frequency oscillations (HFO, 50-70 Hz) were detected using GUI RIPPLELAB in MatLab (Navarrete et al., 2016). Based on the dynamics of hippocampal ripples, SWDs were divided into three clusters, which might represent different seizure types in reference to the involvement of hippocampal processes. This might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. A significant reduction to nearly zero-ripple-density was found 4-8 s prior to SWD onset and during 4 s immediately after SWD onset. It follows that hippocampal ripples were not just passively blocked by the onset of SWDs, but they were affected by spike-wave seizure initiation mechanisms. Hippocampal HFO were reduced during the preictal, ictal and postictal periods in comparison to the baseline. Therefore, hippocampal HFO seemed to be blocked with spike-wave seizures. All together, this might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. Further investigation of processes underlying SWD-related reduction of hippocampal ripples and HFO oscillations may help to predict epileptic attacks and explain cognitive comorbidities in patients with absence epilepsy.

Spike-Wave Seizures, NREM Sleep and Micro-Arousals in WAG/Rij Rats with Genetic Predisposition to Absence Epilepsy: Developmental Aspects.

The current study was done in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats, which are genetically prone to develop spontaneous spike-wave discharges (SWDs) and are widely used as a genetic model of absence epilepsy. Here, we examined functional links between sleep and spike-wave epilepsy in aging WAG/Rij rats using advanced techniques of EEG analysis. SWDs, periods of NREM sleep and micro-arousals were automatically detected in three-channel epidural EEG recorded in freely moving WAG/Rij rats consequently at the age 5, 7 and 9 months. We characterized the developmental profile of spike-wave epilepsy in drug-naïve WAG/Rij rats and defined three epi-phenotypes-severe, mild and minor epilepsy. Age-related changes of SWDs were associated with changes in NREM sleep. Several signs of NREM sleep fragmentation were defined in epileptic WAG/Rij rats. It seems that spike-wave epilepsy per se promotes micro-arousals during NREM sleep. However, subjects with a higher number of micro-arousals (and NREM sleep episodes) at the age of 5 months were characterized by a reduction of SWDs between 5 and 7 months of age.

Whisker trimming during infanthood modifies the development of spike-wave discharges and behavioral sequences in IntelliCage impulsivity paradigm in adult WAG/Rij rats.

Whisker system in rats undergoes rapid development during the first postnatal weeks. Neonatal whisker trimming increases excitability in the somatosensory cortex and affects exploratory behavior at adult ages. WAG/Rij rats are genetically predisposed to develop absence seizures in adulthood, and whisker trimming during three postnatal weeks aggravates epileptic activity in these rats. It is assumed that behavioral performance in adult WAG/Rij rats is influenced (1) by absence epilepsy and (2) by whisker trimming during the short period around the onset of active whisker movements, PN9-16. We examined the effect of whisker trimming in WAG/Rij rats during PN9-16 on spike-wave discharges (SWD, EEG hallmark of absence epilepsy). We found that 77% of WAG/Rij rats showed pronounced SWD (epileptic phenotype), and the rest did not (non-epileptic phenotype). At the age of 5 m, epileptic trimmed rats showed more SWD than epileptic control rats. Age-related increase of SWD was found only in the control group, suggesting that whisker trimming during PN9-16 led to an earlier maturation of SWD. Goal-directed behavior was examined in all rats at the age of 4-4.5 m using IntelliCage impulsivity paradigm. In order to optimize the analysis of behavioral data, we combined several Python packages into a single processing pipeline. Early life whisker trimming altered behavioral sequences and strategy of exploration in adulthood, suggesting reduced whisker sensitivity in the trimmed rats. Epileptic WAG/Rij rats at 4-4.5 months showed only a slight learning impairment during later stages of IntelliCage impulsivity paradigm, which may be associated with the early stage of development of SWD.

Sleep Disturbances in Rats With Genetic Pre-disposition to Spike-Wave Epilepsy (WAG/Rij).

Wistar Albino Glaxo Rijswijk (WAG/Rij) rats are widely used in basic and pre-clinical studies as a valid genetic model of absence epilepsy. Adult WAG/Rij rats exhibit generalized 8-10-Hz spike-wave discharges (SWDs) in the electroencephalogram. SWDs are known to result from thalamocortical circuit dysfunction, and this implies an intimate relationship between slow-wave EEG activity, sleep spindles, and SWDs. The present mini review summarizes relevant research on sleep-related disturbances associated with spike-wave epilepsy in WAG/Rij rats in the domain of slow-wave sleep EEG and microarousals. It also discusses enhancement of the intermediate stage of sleep. In general, sleep EEG studies provide important information about epileptogenic processes related to spike-wave epilepsy.

Spike-wave seizures, slow-wave sleep EEG and morphology of substantia nigra pars compacta in WAG/Rij rats with genetic predisposition to absence epilepsy.

Spike-wave discharges (SWDs) are EEG hallmarks of absence epilepsy, and they spontaneously appear in adult WAG/Rij rats. SWDs are known to be vigilance-dependent and are modulated by monoaminergic mechanisms. It is also known that loss of neurons in the center of the nigrostriatal dopamine system, substantia nigra pars compacta (SNc), is associated with a variety of sleep disorders. We hypothesized that a disorder of the nigrostriatal dopamine system described for WAG/Rij rats might facilitate generation of SWDs through changes in vigilance state and the quality of sleep. Our study was conducted in 'epileptic' and 'non-epileptic' phenotype (less than 1 SWDs per h). Analysis included (1) EEG examination, i.e., analysis of SWDs, rudimentary SWDs and slow wave sleep EEG and (2) microstructural examination of SNc, i.e., measuring its size and the number of neurons and glial cells. No differences in size and cellular content of SNc were found between 'epileptic' and 'non-epileptic' phenotypes. Meanwhile in 'epileptic' subjects, the number of SWDs correlated with the number of neurons in SNc (SWDs more frequently occurred in subjects with fewer neurons in SNc). Rudimentary SWDs were found in both phenotypes. No differences in number and duration of rudimentary SWDs were found between 'epileptic' and 'non-epileptic' phenotypes. Spike-wave EEG activity showed strong association with the number of neurons in SNc: subjects with fewer neurons in SNc were characterized by higher number of SWDs and longer rudimentary SWDs. In sum, our data suggested that intense epileptic EEG activity (in the form of SWDs and rudimentary SWDs) might lead to sleep disruption. However, the lack of direct correlations between sleep parameters and SWDs number indicated that the link between sleep features, SNc cellularity and spike-wave EEG activity could be more complex than we had expected.

Automatic wavelet-based assessment of behavioral sleep using multichannel electrocorticography in rats.

PURPOSE: During the last decade, the reported prevalence of sleep-disordered breathing in adults has been rapidly increasing. Therefore, automatic methods of sleep assessment are of particular interest. In a framework of translational neuroscience, this study introduces a reliable automatic detection system of behavioral sleep in laboratory rats based on the signal recorded at the cortical surface without requiring electromyography. METHODS: Experimental data were obtained in 16 adult male WAG/Rij rats at the age of 9 months. Electrocorticographic signals (ECoG) were recorded in freely moving rats during the entire day (22.5 ± 2.2 h). Automatic wavelet-based assessment of behavioral sleep (BS) was proposed. The performance of this wavelet-based method was validated in a group of rats with genetic predisposition to absence epilepsy (n=16) based on visual analysis of their behavior in simultaneously recorded video. RESULTS: The accuracy of automatic sleep detection was 98% over a 24-h period. An automatic BS assessment method can be adjusted for detecting short arousals during sleep (microarousals) with various duration. CONCLUSIONS: These findings suggest that automatic wavelet-based assessment of behavioral sleep can be used for assessment of sleep quality. Current analysis indicates a temporal relationship between microarousals, sleep, and epileptic discharges in genetically prone subjects.

Active avoidance learning in WAG/Rij rats with genetic predisposition to absence epilepsy.

Neurological disorders are often accompanied by impairment of memory, attention deficit that cause learning difficulties. Better understanding of learning problems in neurological patients might help to improve the quality of their life. Here we studied the character of fear-based associative learning using the standard active avoidance test in WAG/Rij rats with genetic predisposition to absence epilepsy. Electroencephalographic properties of spike-wave seizures (i.e., hallmarks of absence epilepsy) were examined at the age of 5 and 7 m. Around 24 % of rats did not express epileptic activity despite genetic predisposition. In the active avoidance test, 6 m old rats with the epileptic phenotype needed more trails to obtain the first avoidance than non-epileptic rats, but showed the same number of avoidances to reach the learning criterion. The total time of spike-wave activity positively correlated with the outcomes of avoidance performance only in subjects with severe epilepsy, but not in subjects with mild epilepsy. In order to evaluate early sensory (epigenetic) factors governing cognitive comorbidities in adult WAG/Rij rats, we performed bilateral whisker trimming during PN1-8 and PN9-16. This led to a quicker development of SWD, but did not influence cognitive abilities at the age of 6 m. In summary, epileptic WAG/Rij rats had difficulties with executive functions before the first avoidance of adverse stimulus, rather than impairment of memory after the first avoidance. Our data assume that cognitive comorbidities in epileptic WAG/Rij rats primarily may relate to executive deficit during the initial stage of avoidance test and secondary - to impairment of short-term memory. This fits well to outcomes of clinical studies in patients with generalized epilepsy.

Slow-wave activity preceding the onset of 10-15-Hz sleep spindles and 5-9-Hz oscillations in electroencephalograms in rats with and without absence seizures.

Cortico-thalamocortical networks generate sleep spindles and slow waves during non-rapid eye movement sleep, as well as paroxysmal spike-wave discharges (i.e. electroencephalogram manifestation of absence epilepsy) and 5-9-Hz oscillations in genetic rat models (i.e. pro-epileptic activity). Absence epilepsy is a disorder of the thalamocortical network. We tested a hypothesis that absence epilepsy associates with changes in the slow-wave activity before the onset of sleep spindles and pro-epileptic 5-9-Hz oscillations. The study was performed in the WAG/Rij genetic rat model of absence epilepsy and Wistar rats at the age of 9-12 months. Electroencephalograms were recorded with epidural electrodes from the anterior cortex. Sleep spindles (10-15 Hz), 5-9-Hz oscillations and their slow-wave (2-7 Hz) precursors were automatically detected and analysed using continuous wavelet transform. Subjects with electroencephalogram seizures (the "epileptic" phenotype) and without seizure activity (the "non-epileptic" phenotype) were identified in both strains. It was found that time-amplitude features of sleep spindles and 5-9-Hz oscillations were similar in both rat strains and in both phenotypes. Sleep spindles in "epileptic" rats were more often preceded by the slow-wave (~4 Hz) activity than in "non-epileptic" rats. The intrinsic frequency of slow-wave precursors of sleep spindles and 5-9-Hz oscillations in "epileptic" rats was 1-1.5 Hz higher than in "non-epileptic" rats. In general, our results indicated that absence epilepsy associated with: (a) the reinforcement of slow waves immediately prior to normal sleep spindles; and (b) weakening of amplitude growth in transition "slow wave → spindle/5-9-Hz oscillation".

Developmental milestones and behavior of infant rats: The role of sensory input from whiskers.

Developmental milestones are behavioral and physical skills which are considered as markers of neurodevelopment. In rodents, sensory input from whiskers plays a crucial role in development of brain functions. Development of whisker system in rats includes the early period of passive whisker touch (PN1-8) before the onset of coordinated whisker movements which underlie active sensing. Inasmuch as transitioning from passive to active sensing requires a strong sensorimotor integration, we assume that the effect of whisker deprivation during the period of passive touch is unfavorable for neurodevelopment, but deprivation after the onset of active sensing might elicit less harmful effect due to compensatory neuroplalstic changes. Here we examined the effect of complete whisker trimming (WT) in WAG/Rij rats during PN1-8 and PN9-16 (active sensing) on achieving developmental milestones (e.g., eyelid opening, walking, self-grooming, rearing activity, physical maturation of forelimbs), locomotor activity and body weight. Control groups underwent sham trimming during the same periods. WT during PN1-8 caused a delay in achieving all investigated milestones, but WT during PN9-16 delayed only self-grooming. Both WT/sham trimming during PN9-16 caused a delay in explorative behavior, but accelerated self-grooming. These changes are likely to link with the effect of manipulations during PN9-16 in previously unhandled pups, but not specifically with WT. In general, developmental milestones appeared to be an informative tool to access neurodevelopment in rat pups and might have a translational value for studying developmental disorders during early life.

Statistical Properties and Predictability of Extreme Epileptic Events.

The use of extreme events theory for the analysis of spontaneous epileptic brain activity is a relevant multidisciplinary problem. It allows deeper understanding of pathological brain functioning and unraveling mechanisms underlying the epileptic seizure emergence along with its predictability. The latter is a desired goal in epileptology which might open the way for new therapies to control and prevent epileptic attacks. With this goal in mind, we applied the extreme event theory for studying statistical properties of electroencephalographic (EEG) recordings of WAG/Rij rats with genetic predisposition to absence epilepsy. Our approach allowed us to reveal extreme events inherent in this pathological spiking activity, highly pronounced in a particular frequency range. The return interval analysis showed that the epileptic seizures exhibit a highly-structural behavior during the active phase of the spiking activity. Obtained results evidenced a possibility for early (up to 7 s) prediction of epileptic seizures based on consideration of EEG statistical properties.

Neonatal whisker trimming in WAG/Rij rat pups causes developmental delay, encourages maternal care and affects exploratory activity in adulthood.

WAG/Rij rats are genetically predisposed to absence epilepsy. Maternal behavior in WAG/Rij female rats is known to differ from that in non-epileptic females. We hypothesize that (1) mother's behavior may be changed as response to changes in pup's conditions; (2) sensory deprivation at the neonatal age affect learning and behavior in adulthood. All whiskers in WAG/Rij rat pups were trimmed daily during PN1-PN8. Maternal behavior was examined during the same period. It was found that in the control group, WAG/Rij females often demonstrated abnormally long (>1 min) repetitive purposeless stereotypical actions that were roughly classified as compulsive-like behavior. Mothers of the trimmed pups showed less compulsive-like behavior and more intensively interacted with pups and built better nests. Rat pups in the trimmed group had lower body weight on PN7-PN19 as compared to the control. In the trimmed group, maturation of motor skills and early behavioral patterns (i.e. walking, grooming, vertical activity, motor functions of forelimbs) showed 1-2 days delay in comparison to the control. At the age of 2-2.5 months, the locomotor activity in the trimmed rats differed from the control, but the level of anxiety was the same (the open field and the elevated plus maze). At the age of 6 months, the trimmed and control rats showed no differences in conditioned avoidance learning test, therefore, neonatal whisker trimming did not influence fear-based learning abilities in adulthood. It is hypothesized that an enhanced maternal care is capable to modulate development of brain functions in sensory deprived progeny.