Cortical Somatosensory Neurons in WAG/Rij Rats Transform Firing Evoked by Simulation of Posterior Thalamic Nucleus from Tonic to Phasic at Age of 6 Months.

Functional peculiarities of paralemniscal subdivision of the thalamocortical system were examined in normal Wistar and in WAG/Rij rats genetically prone to absence epilepsy. In 6-7-month-old WAG/Rij characterized by developed epileptic activity, the response of cortical somatosensory neurons to single electrical stimulation of the posterior thalamic nucleus was phasic, whereas in normal Wistar rats, similar reaction was tonic. The study views this phasic response as neural equivalent of spike-wave discharges known as typical EEG symptom of absence epilepsy.

The seasonal sensitivity of brown bear denning phenology in response to climatic variability.

BACKGROUND: For brown bears (Ursus arctos), hibernation is a critical part of the annual life cycle because energy savings during hibernation can be crucial for overwintering, and females give birth to cubs at that time. For hibernation to be a useful strategy, timing is critical. However, environmental conditions vary greatly, which might have a negative effect on the functionality of the evolved biological time-keeping. Here, we used a long-term dataset (69 years) on brown bear denning phenology recorded in 12 Russian protected areas and quantified the phenological responses to variation in temperature and snow depth. Previous studies analyzing the relationship between climate and denning behavior did not consider that the brown bear response to variation in climatic factors might vary through a period preceding den entry and exit. We hypothesized that there is a seasonal sensitivity pattern of bear denning phenology in response to variation in climatic conditions, such that the effect of climatic variability will be pronounced only when it occurs close to den exit and entry dates. RESULTS: We found that brown bears are most sensitive to climatic variations around the observed first den exit and last entry dates, such that an increase/decrease in temperature in the periods closer to the first den exit and last entry dates have a greater influence on the denning dates than in other periods. CONCLUSIONS: Our study shows that climatic factors are modulating brown bear hibernation phenology and provide a further structuring of this modulation. The sensitivity of brown bears to changes in climatic factors during hibernation might affect their ability to cope with global climate change. Therefore, understanding these processes will be essential for informed management of biodiversity in a changing world.

The Responses of Neurons of the Somatosensory Cortex to Stimulation of the Posterior Thalamus (PO) in WAG/Rij Rats Genetically Predisposed to Absence Epilepsy.

In genetically predisposed WAG/Rij rats and healthy Wistar rats, we studied functioning of the paralemniscal region of the thalamo-cortical system. The responses of neurons of the somatosensory cortex to single electrical stimulation of the posterior nucleus of the thalamus were recorded in two- to three-monthold rats within the period when the epileptic activity was not developed. We revealed lower number of shortterm inhibitory responses in WAG/Rij rats as compared to Wistar rats. This may create preconditions for the spreading of spike-wave activity in the somatosensory cortex, which is an electrophysiological sign of absence epilepsy.

Compensatory Changes in the Brain Dopaminergic System of WAG/Rij Rats Genetically Predisposed to Absence Epilepsy.

Involvement of the brain dopaminergic system in the age-related dynamics of absence epilepsy in WAG/Rij rats was examined by histological, immunohistochemical, and electrophysiological (EEG) methods. We revealed reduced expression of dopamine receptors in various brain structures prior to first manifestations of the disease (at the age of 1-3 months), reduced density of neurons in the center of nigrostriatal system (substantia nigra pars compacta) in 10-month-old rats in comparison with 1-month-old rats, and positive correlation between neural density in the substantia nigra and intensity of epileptic activity in EEG. It is hypothesized that loss of dopaminergic neurons and reduced nigrostriatal dopaminergic innervation of the brain could prevent the development of absence epilepsy in WAG/Rij rats.

[Thalamo-Cortical Mechanisms of Initiation, Maintenance and Termination of Spike-wave Discharges at WAG/Rij rats].

Generalized spike and wave discharges (SWDs) are generated within the cortico-thalamo-cortical system, being an electroencephalographic sign of absence epilepsy. The current work aims to identify mechanisms of SWD initiation, maintenance and termination. Dynamics and directionality of mutual interactions between neocortex (occipital (OC) and frontal (FC) cortex) and thalamus (reticular (RTN) and ventral postero medial (VPM) thalamic nuclei) were investigated. SWD initiation process is revealed several seconds before seizure onset in interaction between all brain areas, except intrathalamic pair (RTN-VPM). This process begins at different moments relatively to SWD onset. The interaction increase is observed earlier and most obviously when thalamus and OC drive FC. The maintenance process (the first few seconds of SWD) is accompanied with high level interaction inside thalamus and increase of driving from thalamus to occipital cortex. Thus interaction from thalamus and occipital cortex to frontal cortex and influence to VPM occur to be below baseline level. At the SWD offset thalamo-cortical interactions were found to return to baseline level quickly.

[EEG in altricial pied flycatcher nestlings during the functional sates related with natural behavior cycle].

Electrical brain activity accompanying various forms of behavior was studied in 11-day-old pied flycatcher nestlings. Wavelet analysis of EEG, recorded from symmetrical areas of caudomedial nidopallium (higher avian auditory center) during rest, passive and active wakefulness and movements showed that the major rhythmical EEG component was confined to low-frequency range in all four states. The significant difference from other states was observed only during movements: spectral power in the range of 1-3 Hz decreased while that in the range of 5-20 Hz--increased. The range of 3-5 Hz revealed, in all functional states, the interhemispheric asymmetry of spectral power that could be due to asymmetrical embryonic development of avian visual projections. Active wakefulness and movements were characterized by high positive correlations between spectral power in right and left hemispheres. During rest this correlation was negative. The correlation values during passive wakefulness and rest were rather low that could indicate disintegration of neural connections.

EEG biomarkers of activation of the lymphatic drainage system of the brain during sleep and opening of the blood-brain barrier.

The lymphatic drainage system of the brain (LDSB) is the removal of metabolites and wastes from its tissues. A dysfunction of LDSB is an important sign of aging, brain oncology, the Alzheimer's and Parkinson's diseases. The development of new strategies for diagnosis of LDSB injuries can improve prevention of age-related cerebral amyloid angiopathy, neurodegenerative and cerebrovascular diseases. There are two conditions, such as deep sleep and opening of the blood-brain-barrier (OBBB) associated with the LDSB activation. A promising candidate for measurement of LDSB could be electroencephalography (EEG). In this pilot study on rats, we tested the hypothesis, whether deep sleep and OBBB can be an informative platform for an effective extracting of information about the LDSB functions. Using the nonlinear analysis of EEG dynamics and machine learning technology, we discovered that the LDSB activation during OBBB and sleep is associated with similar changes in the EEG θ-activity. The OBBB causes the higher LDSB activation vs. sleep that is accompanied by specific changes in the low frequency EEG activity extracted by the power spectra analysis of the EEG dynamics combined with the coherence function. Thus, our findings demonstrate a link between neural activity associated with the LDSB activation during sleep and OBBB that is an important informative platform for extraction of the EEG-biomarkers of the LDSB activity. These results open new perspectives for the development of technology for the LDSB diagnostics that would open a novel era in the prognosis of brain diseases caused by the LDSB disorders, including OBBB.

[Reduction of the number of neurons in substantia nigra (Pars compacta) positively correlates with a reduction of seizure activity in WAG/Rij rats].

In WAG/Rij rats with a genetic predisposition to absence epilepsy, age-related dynamics of seizure activity in the frontal EEG was studied. In parallel, cellular content in substantia nigra was analyzed at the age of 1 and 10 months. In 10-months animals, the number of neurons in substantia nigra showed a profound decrease, whereas the number of glial calls increased. In parallel to that, the incidence of epileptic discharges and their duration significantly increased between 5 and 9 months of age. Positive correlations were revealed between the incidence of epileptic discharges and the number of neurons in substantia nigra suggesting that animals with lower number of neurons in SN expressed fewer absence seizures, and vice versa. It was suggested that reduction of neurons in substantia nigra is an adaptive process to prevent progressive development of absence seizures.

[Age-related changes in time-frequency structure of sleep spindles in EEG in rats with genetic predisposition to absence epilepsy (Wag/Rij)].

It is known that sleep spindles are produced by thalamo-cortical system spontaneously during the slow-wave sleep; pathological processes in thalamo-cortical network might cause absence epilepsy. The aim of this study was to examine age-dependent changes in time-frequency structure of sleep spindles in parallel to a progressive increase in amount of absence seizures in WAG/Rij rat model. EEG was consistently recorded at the age of 5, 7 and 9 months by means of epidural electrodes implanted in the frontal cortex. Continuous wavelet transform was used for automatic identification and further time-frequency analysis of sleep spindles in EEG. It was found that the mean duration of epileptic discharges and total duration of epileptic activity increased with age, whereas the length of sleep spindles decreased. Mean frequency of oscillations within a spindle was used as a criterion for dividing sleep spindles in three categories: "slow" (9.3 Hz), "tr ansitional" (11.4 Hz) and "fast" (13.5 Hz). "Slow" and "transitional" spindles in 5-months animals displayed an increase in frequency from the beginning towards the end. It was shown that the higher incidence of epilepsy corresponded to the lower duration of sleep spindles (all types). Mean frequency of "transitional" and "fast" spindles was higher in rats with more intensive epileptic discharges. In general, high epileptic activity in WAG/Rij rats corresponded to the most substantial changes within "transitional" spindles, whereas changes within slow and fast spindles were moderate.

[The effect of early sensory experience on development of neuron functional properties in the area of vibrissal projection in the rat neocortex].

The role of specific sensory inflow in the functional maturation of neurons in the area of vibrissal projections in the somatosensory cortex of rats was studied. Animals were subjected to bilateral trimming of whiskers during the first three weeks of postnatal ontogenesis. Quantitative and qualitative characteristics of neuronal responses were analyzed in the "lemniscal" layers IV and Vb and "paralemniscal" layer Va in junior (27-40 PN days) and elder (41-57 PN days) rats. The immediate effect of deafferentation in younger animals consisted in an increase in excitatory responses, which correlated with a deficit of inhibitory reactions. In animals subjected to vibrissectomy, atypical responses were observed in the "lemniscal" and "paralemniscal" layers. This effect may be caused by a derangement of distribution of thalamic afferents in the somatosensory cortex. Elder animals in vibrissectomized group displayed an increase in inhibitory reactions, i.e., the long-term effect of vibrissectomy is the actualization of inhibitory mechanisms.

[Lemniscal and paralemniscal afferent pathways in rodents' trigeminal system are integrated at the level of the somatosensory cortex].

The present paper demonstrates a functional interaction between lemniscal and paralemniscal sensory pathways in vibrissal projection area in the somatosensory cortex in rats. Single unit activity was recorded in layers IV, Va and Vb. It is found that mechanical stimulation of whiskers elicits characteristic 'lemiscal' (phasic) responses mainly in layers IV and Vb, while neurons in layer Va show typical 'paralemiscal' (tonic). Our data reveal that neurons in layers IV and Vb comprise a population of rapidly adapting neurons and neurons in layer Va are slowly adapting. Our findings suggest that the somatosensory cortex receive lemniscal and paralemniscal projections. A cooperation of lemniscal and paralemniscal projection systems at the somatosensory cortex and strong adaptive capabilities of cortical neurons could increase an accuracy of tactile perception, therefore animals can fine discrimination of sensory stimuli in a given environment.

[Cytomorphological features of the neocortex in rats with genetic predisposition to absence epilepsy].

The aim of the study was to examine putative microstructural changes in the neocortex which accompany absence epilepsy. Rat strains WAG/Rij as a genetic model of absence epilepsy and ACI (control) were examined. Brain slices were stained after Nissl; neuronal and glial cells were identified and counted in the somatosensory, motor, and cingular cortices (in layers II/III, V, and VI, individually). In WAG/Rij rats, the density of neurons in the superficial layers (II/III) of the motor cortex appeared to be lower than in healthy control rats, whereas the density ofglial cells in WAG/Rij rats was higher. In the deep layers of the somatosensory and cingular areas, the density ofglial cells in WAG/Rijrats rats was lower as compared to control rats. The results demonstrate that absence epilepsy is associated with cytomorphological changes in the neocortex.

The effects of restricting afferent input during early ontogenesis on evoked activity of projection neurons depend on the maturity of the sensory inputs.

Experiments were performed on 28 Wistar rats, of which 14 were subjected to unilateral denervation of the forelimb (by dissection of the median nerve) on day 13 of postnatal ontogenesis. The effects of restriction of sensory input on baseline and evoked somatosensory cortex neuron activity in the areas corresponding to the representation of the intact fore- and hindlimbs were studied. According to the proximal-distal rule of maturation, the sensory input from the forelimbs was completely formed by the moment at which deafferentation was performed, while the sensory input from the hindlimbs was still incompletely mature. Opposite changes were found to occur in areas receiving more or less mature afferent inputs. In the projection zone of the less mature input (from the hindlimbs), neurons showed a lower frequency of baseline activity and stimulation of the sciatic nerve evoked significantly more activatory responses and an increase in the duration of short-latency activatory responses. In the projection zone of the more mature sensory input (from the forelimb), stimulation of the intact median nerve evoked significantly more inhibitory responses and fewer complex responses. Thus, normal formation of normal brain neuron activity requires an adequate sensory input.

[Vibrissectomy in rats in early ontogeny leads to disordered functional properties of the cortical projection neurons]. / Vibrisséktomiia u krys v rannem ontogeneze privodit k narusheniiu funktsional'nykh svoistv proektsionnykh neironov kory.

Vibrissae trimming during the first 20 days of postnatal life caused alternations of the properties of the receptive fields of single neurons in the barrel-field cortex in rats. The following changes were found in the deafferented cortex: (i) an extension of the receptive fields of single neurons as judged from an increase in the number of vibrissae with short-latency excitatory responses to stimulation and (ii) a depression of the inhibitory receptive field tuning mechanisms.

[The effect of the limitation of afferent inflow in early ontogeny on the evoked activity of projective neurons depends on the degree of the maturity of the sensory inputs]. / Vliianie ogranicheniia afferentnogo pritoka v rannem ontogeneze na vyzvannuiu aktivnost' proektsionnykh neironov zavisit ot stepeni zrelosti sensornykh vkhodov.

The study is focused on the influence of a partial limitation of the sensory inflow in rat pups on the development of the sensory systems, which mature earlier and later. In accordance with the ontogenetic rule of proximal-distal maturation, the sensory inflow from the forelimbs matures faster than that from the hindlimbs. Fourteen Wistar rat pups (from 28) were deafferented on the 13th day of postnatal ontogeny (a small portion of the median nerve was unilaterally dissected). The background and evoked activity of single neurons was recorded in 26-47-day-old pups in the somatosensory cortex (in the projection areas of the intact n. medianus, which matures earlier, and n. ischiadicus, which matures later). The changes in firing activity produced by deafferentation were observed. In the projection area of the intact forelimb of the denervated rats, the incidence of inhibitory responses significantly increased, whereas the incidence of completes responses significantly decreased. In the hindlimb projection area of the denervated animals the background firing rate was significantly lower and the incidence of activation responses was increased.

[The effect of forelimb deafferentation in early postnatal ontogeny on the development of synaptic transmission in the hippocampus]. / Vliianie deafferentatsii perednei konechnosti v rannem postnatal'nom ontogeneze na formirovanie sinapticheskoi peredachi v gippokampe.

Hippocampal slices from 15-20-day-old Wistar rats were used to study the development of some features of synaptic transmission in hippocampus and the influence of partial limitation of the sensory inflow in the early ontogeny of this transmission. The dynamics of population spike changes was observed in the CA1 hippocampal field in response to stimulation of Schaffer collaterals. The early ontogenetic limitation of the sensory inflow was accomplished by cutting n. medianus on the 13th day. Between the 15th and 20th days, the dynamics of the population spike amplitude increase in the control and experimental animals was similar, however, the response amplitude of the control rats remained higher than in the experimental animals throughout the whole period of observation. It is suggested that the partial limitation of sensory inflow from a forelimb at the early stages of the ontogeny alters the formation of synaptic transmission in hippocampus.

[Sensory information--an important factor in ontogeny]. / Sensornaia informatsiia--vazhnyi faktor ontogeneza.

Ontogenetic process reveals a row of consecutive stages characterized by the gradual increase in complexity and by the changing specificity of sensory mechanisms basic for the adaptive behavior of the young. The study examines the mechanisms of interaction among different sensory systems during the formation of early behavioral patterns and analyzes why, at a certain stage of development, a particular sensory stimulus loses its efficacy in the organization of a given behavior and is substituted by another one, previously ineffective. A special attention is paid to formation of behavior based on sensory information within the limits of ontogenetically fixed developmental critical periods and to the role of the early sensory experience in learning in adult animals.

[Protective properties of recombinant IgA1 protease from meningococcus].

The study of enzymatic and protective properties of recombinant IgA1 protease in active and mutant form showed that active form of IgA1 protease exhibited species - and type-specificity for mouse and human immunoglobulins. Mutant form, which did not exhibit enzymatic activity, had protective properties against meningococcal infection, induced by meningococcus serogroup A, B and C protecting the mice from lethal infection by living virulent culture of heterologous serogroups of meningococcus. Obtained results make it possible to consider IgA1 protease as a perspective preparation at the stages of development of polyvalent vaccine for protection the people from meningococcal infection of various etiology.

The lemniscal and paralemniscal pathways of the trigeminal system in rodents are integrated at the level of the somatosensory cortex.

The studies reported here demonstrate that the projection representation of the whiskers in the somatosensory cortex in rats is the area at which afferent streams arriving via the lemniscal and paralemniscal projections interact. The responses of neurons in layers IV, Va, and Vb to mechanical stimulation of single whiskers were studied. Neurons in layers IV and Vb were found to show more frequent phasic responses (typical of the lemniscal system), while those in layer Va produced predominantly tonic responses (typical of the paralemniscal system). These characteristics of adaptive-plastic rearrangements of cortical neuron activity in response to constant stimuli may result from intracortical cooperative interactions between the lemniscal and paralemniscal projection systems, which, overall, produces a precise qualitative assessment of the perceived stimulus in its specific context.