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N A Lazareva

Publications and source records attributed to N A Lazareva.

At least 19 recordsLinked to original sources

The time course of disinhibition of visual cortex neurons and sensitivity to cross-shaped figures.

The relationship between the responses of 74 neurons in field 17 of the cat cortex to presentation of cross-shaped figures flashing in their receptive fields and the asynchronicity with which the lines of the figures were presented were investigated. The cross sensitivity of neurons was studied with simultaneous, leading, and delayed activation of the disinhibitory zone of the receptive field in relation to the time at which its major excitatory and end-stopping inhibitory zones were stimulated. Two types of temporal interaction were identified between the receptive field zones determining cross sensitivity. In cells of the first type (14 of 23 cells), the response was maximal in conditions of simultaneous stimulation of the major and disinhibitory zones of the receptive field; neurons of the second type (nine of 23 cells) showed the opposite temporal relationship. Digital simulation showed that cross sensitivity in neurons of the first type was supported by disinhibition of end-stopping inhibition, while in neurons of the second type it depended on a combination of disinhibitory and convergence mechanisms.

Action Potentials↗

Studies of the effects of central administration of beta-amyloid peptide (25-35): pathomorphological changes in the Hippocampus and impairment of spatial memory.

The possible link between amnesia induced by central administration of beta-amyloid (25-35) (Abeta(25-35)) and neurodegenerative changes in the hippocampus was studied. Male Wistar rats received single intracerebroventricular injections of Abeta(25-35) at a dose of 15 nmoles and one month later were trained in an eight-arm radial maze. Training was followed by histological assessment of the state of the hippocampus on brain sections stained with hematoxylin and eosin. Abeta(25-35) induced impairments in long-term (reference) and working memory on testing in the maze. There was a moderate reduction in the number of neurons in hippocampal field CA1; there was no change in the number of cells in field CA3. The numbers of errors made by the animals on testing in the maze were found to correlate negatively with the numbers of nerve cells in hippocampal field CA1. Thus, this is the first demonstration that impairments of learning and memory induced by single doses of Abeta(25-35) are specifically associated with neurodegenerative changes in hippocampal field CA1 in rats.

Amyloid beta-Peptides↗

[Responses of neurons in cat visual cortex with sensitivity to bar and cross-like figure].

In the cat primary visual cortex (area 17) the response magnitude and latency were studied in 280 neurons sensitive to bar or cross-like-figure. Under natural conditions half of the studied 195 cells preferred bar (first group) or cross (second group). In the first group responses to both figures were near equal, while in the second one cross evoked much stronger response. Response latencies with the optimal bar in the first group were shorter than in the second group and longer to a cross than to a bar while in the second group they were considerably shorter to a cross than to bar. Under local blockage of GABA-ergic inhibition by microiontophoretic application of bicuculline about one-fourth of 85 neurons generated greater responses and were bar-sensitive irrespective to presence or absence of inhibition. Other neurons were cross-sensitive at least in one of the conditions (with and/or without of inhibition). They responses grew under bicuculline action relatively more than in the first group. Significance of the data obtained for tuning to image features and temporal succession of their detection is discussed.

Action Potentials↗

Central administration of a caspase inhibitor impairs shuttle-box performance in rats.

Recent studies suggest that caspase-3-mediated mechanisms are essential for neuronal plasticity. N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val- Asp(OMe)-fluoromethyl ketone (z-DEVD-fmk), a caspase inhibitor with predominant specificity toward caspase-3, has been shown to block long-term potentiation in hippocampal slices. Intrahippocampal infusion of a caspase-3 inhibitor to rats has been shown to significantly impair spatial memory in the water maze. The present work was designed to study whether i.c.v. administration of a caspase-3 inhibitor z-DEVD-fmk impairs learning in other tasks related to specific forms of memory in rats. The rats received bilateral injections of z-DEVD-fmk or N-benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone (z-FA-fmk) ("control" peptide) at a dose of 3 nmol. Administration of z-DEVD-fmk significantly decreased the number of avoidance reactions in some blocks of trials in the active avoidance (shuttle box) learning, while z-FA-fmk had no effect as compared with intact rats. However, only a slight effect of the caspase inhibitor across the session was found. z-DEVD-fmk impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed most expressed z-DEVD-fmk-related inhibition of the enzyme activity (about 30%) in the fronto-parietal cortex. A similar effect was close to significant in the hippocampus, but not in the other cerebral structures studied. In primary cultures of cerebellar neurons z-DEVD-fmk (2-50 microM) inhibited caspase-3 activity by 60-87%. We suggest that moderate inhibition of caspase-3 resulting from the central administration of z-DEVD-fmk to rats may impair active avoidance learning. Taking into account previous data on the involvement of neuronal caspase-3 in neuroplasticity phenomena we assume that the enzyme may be important for selected forms of learning.

Animals↗

Dynamic changes in the tuning of striate neurons to the shapes of cross-shaped figures.

Time slice analysis was used to study the dynamics of tuning to the shapes of cross-shaped figures flashing in the receptive fields of 83 neurons in the primary visual cortex (field 17) of the cat brain. Tuning was assessed in terms of the numbers of spikes in the overall response and its sequential 20-msec fragments. Only 11.7% of neurons produced reproducibly developing spike responses to a given shape (defined as the angle between the lines), i.e., had a preferred cross-shaped figure. In the remaining cases (88.3%), tuning of neurons to the shape of the cross showed dynamic changes. In 7.2% of cases, changes in the preferred shape of the cross occurred monophasically; changes were biphasic in 27.0% of cases, while in the remaining 54.1% of cases, the dynamics in changes in the preferred cross shape were undulatory. The tuning of receptive field zones is assessed as the cause of these effects and their difference from the previously observed dynamics of preferred orientations of single bars and cross-shaped figures; the functional significance of these effects is also discussed.

Action Potentials↗

Studies of the effects of fragment (25-35) of beta-amyloid peptide on the behavior of rats in a radial maze.

Decreases in cognitive functions, particularly long-term (episodic) and working memory, are among the earliest prognostic signs of Alzheimer's disease. The toxicity of beta-amyloid peptide is regarded as a major cause of neurodegeneration and cognitive impairment in this disease. The present report describes studies of the effects of intracerebroventricular administration of beta-amyloid peptide (25-35) (Abeta(25-35)) on the reproduction of a previously assimilated habit consisting of finding food in an eight-arm radial maze in rats. Abeta(25-35) was given bilaterally at doses of 15 and 30 nmol/animal seven days after preliminary training. Testing was performed 60 days after peptide administration. The results showed that Abeta(25-35) impaired working memory in rats without having any significant effect on the retention of responses. We were unable to demonstrate any relationship between memory impairment and the dose of peptide given. These data provide evidence of the ability of Abeta(25-35) to produce greater degradation of working memory function than long-term memory function.

Amyloid beta-Peptides↗

[Temporal course of disinhibition of the visual cortex neurons and their sensitivity to cross-like figures].

In acute experiments with narcotized and paralyzed cats, we studied responses of 74 striate neurons to cross-like figure under synchronous and asynchronous presentation of its lines. The aim of the study was to characterize the temporal course of interaction between three RF zones: main excitatory, end-inhibitory, and side disinhibitory ones. Previously we have found that this interaction is responsible for sensitivity to a cross in near 3/4 of cat striate cells with such sensitivity. In neurons with sensitivity to a cross, we found two types of temporal interaction between zones of RF. In the 1st type cells (14/23), the response significantly increased if the disinhibitory and the main excitatory zones of RF were stimulated simultaneously. Neurons of the 2nd type (9/23) revealed opposite temporal function: synchronous activation of RF zones evoked a minimal response. Simulation shows that the 1st type of behavior is connected with disinhibitory mechanism, while that of the 2nd type--with combination of this mechanism with convergence of orientation detectors of the previous functional level.

Animals↗

Single intracerebroventricular administration of amyloid-beta (25-35) peptide induces impairment in short-term rather than long-term memory in rats.

Ample experimental evidence indicates that intracerebral injection or infusion of amyloid-beta peptides (Abeta) to rodents induces learning and memory impairments as well as neurodegeneration in brain areas related to cognitive function. In the present study, we assessed the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Abeta fragment (25-35) at a dose of 15nmol/rat on short-term and long-term memory in rats during the 6-month post-surgery period. The results demonstrate that Abeta(25-35)-induced memory impairments in spontaneous alternation behavior in a Y-maze at 17, 36, and 180 days after the surgery as well as in a social recognition task 110 days post-surgery. Abeta(25-35) also impaired spatial memory in an 8-arm radial maze, but did not influence performance of the step-down passive avoidance task. These results suggest that Abeta(25-35) preferably induces impairments of spatial and non-spatial short-term (working) memory rather than long-term memory in rats.

Amyloid beta-Peptides↗

Administration of aggregated beta-amyloid peptide (25-35) induces changes in long-term potentiation in the hippocampus in vivo.

Intracereroventricular administration of aggregated beta-amyloid protein fragment (25-35) (7.5 nmol/ventricle) was followed one month later by significant changes in the dynamics of long-term potentiation in the hippocampus in vivo, expressed as powerful and stable increases in the amplitude of evoked potentials. This phenomenon may be associated with oxidative stress in the hippocampus, which has previously been demonstrated in this model, and, thus, with disturbances in ion homeostasis.

Amyloid beta-Peptides↗

[Dynamics of tuning to the shape of a cross-like figure in striate neurons].

Dynamics of tuning to the shape of cross-like figure flashed in receptive field was studied in 83 striate neurons by the method of temporal slices. Tuning was estimated by the total number of spikes in the response and by this number in successive fragments of the response with 20 ms steps. It was found that only in 11.7% cases neurons showed stable tuning to the same shape of the preferred figure (an angle between its lines), in other cases (88.3%) during response generation this tuning changes being one-phase (7.2%) or two-phase (27.0%), or undulatory (54.1%). Different dynamical reorganization of receptive field zones is discussed as a possible mechanism of the revealed effects as well as their correlation with previously described dynamics of tuning to orientation of a single bar and a cross in striate cells.

Action Potentials↗

Tuning to Y-like figures in the cat striate neurons.

Sensitivity to symmetric or asymmetric Y-like figures and crosses of different shapes and orientations flashed in the receptive field was studied in 101 neurons of the cat striate cortex (area 17) and compared with their orientation tuning to a single light bar. Selective sensitivity to the Y-like figure (figure/bar response ratio more than 1.25) was found in 78/101 neurons (77.2% of cases) and to the cross-in 54/101 units (53.4%). In 62.5% of neurons with sensitivity to both figures, sensitivity to the Y-like figure was higher than to a cross. Tuning to Y-like figure was typically (60%) selective to both its shape and orientation. The remaining Y-like selective neurons exhibited invariant tuning to orientation and/or shape of the figure. The preferred angles between two lines of Y-like figures were distributed in the range of 22.5-157.5 degrees with slight preference to 90 degrees, while crosses of 45 degrees and 90 degrees angles were preferable. Response magnitudes to a single bar, a Y-like figure and a cross were positively correlated. Possible mechanisms and functional implication of the striate sensitivity to Y-like figures are discussed.

Action Potentials↗

[Disinhibitory zone of the striate neuron receptive field and its sensitivity to the cross-like shape].

Sensitivity of 84 neurones to presentation of cross-form figures was studied in cats as well as the lever length function prior to and after stimulation of the RF disinhibitory zone. Responses to lever length of the cross-sensitive cells were augmented in simultaneous stimulation of the RF. The data obtained suggest involvement of the end inhibition and its blocking by a side-disinhibitory zone of the RF.

Animals↗

Interrelation of tuning characteristics to bar, cross and corner in striate neurons.

Characteristics of responses and background activity, as well as of tuning to a single bar orientation and to cross or corner shape and orientation have been compared in one third (561174) of neurons in the cat striate cortex. Shortening of the response latency to cross vs bar, to corner vs bar and to corner vs cross was revealed in most of the units studied. Direct correlation between the response and tuning characteristics for bar, cross and corner was revealed: units with better tuning to one type of stimulus were typically better tuned to the other types of stimuli. At the middle cortical depth (700-1200 microm from the surface) we found a reliable improvement of response magnitude and latency, cross/bar response ratio and selectivity of tuning in comparison with more superficial and deeper layers. Although we could not find a direct correlation between characteristics of tuning to figures and the type of the receptive field (simple, complex or hypercomplex), our data pointed to a lower cross/bar ratio and selectivity of tuning in the units with small receptive fields. The functional implication of neuronal sensitivity to cross and corner and possible meaning of correlation between their functional characteristics are discussed.

Animals↗

[The effect of oxidative stress on brain nitric oxide synthase activity in vivo and in vitro].

Within 8 days of a 10-min cardiac arrest, accumulation of material reacting with 2-thiobarbituric acid was revealed in the hippocampus (74%) and cerebellum (47%) of male Wistar rats. Oxidative stress was accompanied by a twofold decrease of the nitric oxide synthase activity in the brain tissue. In vitro experiments showed a dose-dependent decrease of nitric oxide synthase activity in the brain homogenates as a result of the oxidative stress induced by hydrogen peroxide or sodium hypochlorite. The findings suggest that the oxidative stress may decrease nitric oxide synthase activity as a result of direct effects of the active oxygen on the enzyme.

Animals↗

The contribution of intracortical inhibition to dynamics of orientation tuning in cat striate cortex neurons.

Orientation tuning of some neurons in cat visual cortex (area 17) revealed successive shifts of the preferred orientation and widening of tuning in time during the first 150 ms after onset of a flashing light bar. The mechanisms of these dynamics and the possible role of intracortical inhibition are still under discussion. In this study we analysed the dynamics using the time slice method before and during blockade of GABAergic inhibition by microiontophoretic application of bicuculline and observed two main types of neuronal behaviour. The first group of neurons (39 of 68 units or 57.4%) with relatively sharp tuning and absence or relatively small shifts of preferred orientation under control conditions increased or developed this shift during bicuculline application. Changes in tuning were observed between 30 and 150 ms after stimulus onset when inhibition was blocked. Neurons of the second group (29 units or 42.6% of cases) displayed pronounced shifts of preferred orientation under control conditions which was typically diminished or lost during blockade of inhibition. The results indicate different contributions of intracortical inhibition to different neurons distinguishing by stability or time dependence of their orientation preference during normal response generation. In one group of striate cells orientation tuning was kept narrow and constant in time by intracortical inhibition, while in another group orientation tuning dynamics are induced by inhibitory mechanisms.

Animals↗

Orientation tuning and receptive field structure in cat striate neurons during local blockade of intracortical inhibition.

The contribution of intracortical inhibition to orientation tuning in the cat striate cortex (area 17) was studied by responses to flashing light bars of different orientations and lengths in 68 single-units before and during microiontophoretical application of bicuculline, a GABAA antagonist, A three-fold increase in the background activity (13.3 +/- 1.3 vs 4.4 +/- 0.5 imp/s) and 4.4-fold increase in the maximal discharge frequency (264.4 +/- 22.3 vs 60.6 +/- 5.3 imp/s) was found in 96.0% of the cells studied during microiontophoresis. In most units all characteristics of orientation tuning significantly changed during application of bicuculline: i) tuning width increased in 76.3% of cells from 52.7 +/- 2.8 degrees in control to 85.2 +/- 4.6 degrees, ii) tuning selectivity diminished in 63.6% of cells by a factor of 1.5, and iii) tuning quality dropped in 68.5% of cases by a factor of 2.5. The threshold ejection current of bicuculline for widening of tuning was in 2/3 of the cells in the range from +10 to +40 nA (+31.0 +/- 4.5 nA) and the maximum effect was obtained in 3/4 of units with +30(-) + 100 nA (+67.1 +/- 6.0 nA). Unmasking of additional excitatory inputs to the studied cells due to blockade of the inputs from inhibitory interneurons in considered as the main mechanism of the described bicuculline effects.

Animals↗

Selective and invariant sensitivity to crosses and corners in cat striate neurons.

Many neurons (56/174, or 32.2%) studied in the cat striate cortex (area 17) increased significantly (by 3.3 times on average) their responses under stimulation by cruciform or corner figures of specific or non-specific shape and orientation flashing in receptive field as compared with single light bar of preferred orientation. Most of these neurons (71.4%) were found to be highly selective to both the shape (the angle between the figure's lines) and orientation of these figures. In the neuronal selection studied we have also found all possible types of invariance of the cross and corner tuning to orientation and/or shape of these figures. We found neurons with selectivity to the form of the figures and invariance to their orientation and, on the contrary, units invariant to shape but selective to orientation. Some cells were found invariant to both the form and orientation of the cruciform or corner figure but highly sensitive to appearance of any such figure in the receptive field. Two main hypotheses about the mechanisms of selective sensitivity to crosses and angles can be considered. They are as follows: an excitatory convergence of two units with different preferred orientations, and intracortical inhibitory interactions. The cells with double orientation tuning for a single bar are found relatively rarely (about 20%), thus making the first suggestion the most unlikely. This circumstance is of special importance since it provides evidence against the hierarchic formation of the higher-order cortical units from a set of lower-order cells that is still under discussion. The units with high sensitivity to cross or corner seem to be ideally suitable for their selection, rather than to serve as classical orientation detectors only.

Animals↗