Vasily Vorobyov

Intracortical Origins of Interocular Suppression in the Visual Cortex

The response of neurons in the primary visual cortex to an optimally oriented grating is usually suppressed quite dramatically when a second grating of, for example, orthogonal orientation is superimposed. Such “cross-orientation suppression” has been implicated in the generation of cortical orientation selectivity and local response normalization. Until recently, little experimental evidence was available concerning the neurophysiological substrate of this phenomenon, although an involvement of intracortical inhibition was commonly assumed. However, Freeman et al. (2002) proposed that cortical cross-orientation suppression is caused by suppression in the thalamus and depression at geniculocortical synapses. Here, we examine a dichoptic form of cross-orientation suppression, termed interocular suppression and thought to be involved in binocular rivalry (Sengpiel et al., 1995a). We show that its dependency on the drift rate of the suppressing stimulus is consistent with a cortical origin; unlike monocular cross-orientation suppression, it cannot be evoked by very fast-moving stimuli. Moreover, we find that previous adaptation to the orthogonal stimulus essentially eliminates interocular suppression. Because adaptation is a cortical phenomenon, this result also argues in favor of a cortical locus of suppression, again unlike monocular cross-orientation suppression, which is not affected by adaptation to the suppressor (Freeman et al., 2002). Finally, interocular suppression is greatly reduced in the presence of the GABA antagonist bicuculline. Together, our study demonstrates that interocular suppression is substantially different from monocular cross-orientation suppression and is mediated by inhibitory circuitry within the visual cortex.

Effects of Digesting Chondroitin Sulfate Proteoglycans on Plasticity in Cat Primary Visual Cortex

Monocular deprivation (MD) during a critical period of postnatal development produces significant changes in the anatomy and physiology of the visual cortex, and the deprived eye becomes amblyopic. Extracellular matrix molecules have a major role in restricting plasticity such that the ability to recover from MD decreases with age. Chondroitin sulfate proteoglycans (CSPGs) act as barriers to cell migration and axon growth. Previous studies showing that degradation of CSPGs by the bacterial enzyme chondroitinase can restore plasticity in the adult rat visual cortex suggest a potential treatment for amblyopia. Here MD was imposed in cats from the start of the critical period until 3.5 months of age. The deprived eye was reopened, the functional architecture of the visual cortex was assessed by optical imaging of intrinsic signals, and chondroitinase was injected into one hemisphere. Imaging was repeated 1 and 2 weeks postinjection, and visually evoked potentials (VEPs) and single-cell activity were recorded. Immunohistochemistry showed that digestion of CSPGs had been successful. After 2 weeks of binocular exposure, some recovery of deprived-eye responses occurred when chondroitinase had been injected into the hemisphere contralateral to that eye; when injected into the ipsilateral hemisphere, no recovery was seen. Deprived-eye VEPs were no larger in the injected hemisphere than in the opposite hemisphere. The small number of neurons dominated by the deprived eye exhibited poor tuning characteristics. These results suggest that despite structural effects of chondroitinase in adult cat V1, plasticity was not sufficiently restored to enable significant functional recovery of the deprived eye.

Weak combined magnetic field affects basic and morphine-induced rat's EEG

The present study was undertaken to find out, whether weak combined magnetic field (CMF) with intensity comparable to that of the Earths static magnetic field can influence the EEG activity of the rats brain at normal (non-treated animals) conditions and after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of morphine in experimental animals bearing chronically implanted electrodes and cannules. Most of the experiments were performed using CMF containing co-linear static (20.9 microT) and alternating sinusoidal (20.9 microT, 48 Hz) components, i.e., tuned for Ca2+-resonance. The effects of the field were estimated by comparison of the averaged EEG frequency spectra in the range of frequencies between 0.8-23 Hz in experimental and control animals. Statistically significant effects of CMF were observed both in non-treated and morphine-treated rats. However, the most profound effect-the drastic power reduction at most EEG frequencies-appeared in the animals subjected to the i.p.-injection of morphine. These results show that weak CMF can influence the spontaneous electrical brain activity. The data obtained are consistent with the findings of other groups demonstrating that weak magnetic fields may drastically modify the effects of both exogenous and endogenous opioids on different basic functions in vertebrates and invertebrates. Possible mechanisms for the observed effects are discussed.

Brief daily binocular vision prevents monocular deprivation effects in visual cortex.

Even short periods of early monocular deprivation result in reduced cortical representation and visual acuity of the deprived eye. However, we have shown recently that the dramatic deprivation effects on vision can be prevented entirely if the animal receives a brief period of concordant binocular vision each day. We examine here the extent to which the cortical deprivation effects can be counteracted by daily periods of normal experience. Cats received variable daily regimens of monocular deprivation (by wearing a mask) and binocular vision. We subsequently assessed visual cortex function with optical imaging of intrinsic signals and visually evoked potential recordings. Regardless of the overall length of visual experience, daily binocular vision for as little as 30 min, but no less, allowed normal ocular dominance and visual responses to be maintained despite several times longer periods of deprivation. Thus, the absolute amount of daily binocular vision rather than its relative share of the daily exposure determined the outcome. When 30 min of binocular exposure was broken up into two 15‐min blocks flanking the deprivation period, ocular dominance resembled that of animals with only 15 min of binocular vision, suggesting that binocular experience must be continuous to be most effective. Our results demonstrate that normal experience is clearly more efficacious in maintaining normal functional architecture of the visual cortex than abnormal experience is in altering it. The beneficial effects of very short periods of binocular vision may prevent any long‐term effects (amblyopia) from brief periods of compromised vision through injury or infection during development.

EEG modifications in the cortex and striatum after dopaminergic priming in the 6-hydroxydopamine rat model of Parkinson’s disease

In rats bearing a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, a single administration of a dopamine receptor agonist (priming) sensitizes the behavioral motor responses to a dopaminergic agonist, administered 3 days after priming. In this study, changes in the electroencephalogram (EEG) frequency spectra were evaluated during priming in unilaterally 6-OHDA-lesioned rats, implanted bilaterally with electrodes both in the somatosensory cortex and striatum. Two weeks after 6-OHDA lesion, rats were primed with apomorphine (0.2 mg/kg) and received a challenge with the D(1) agonist SKF 38393 (3 mg/kg) 3 days later. 6-OHDA lesion modified the EEG pattern mainly in the beta(1) frequency band, in both cortex and striatum. Apomorphine priming produced a power decrease in the beta(1) frequency band, more pronounced in the cortex than in the striatum, as compared to saline-treated rats. Antagonism of NMDA receptor with MK-801, a treatment known to block the development of priming, increased apomorphine inhibitory effect mainly in the striatum, producing the same degree of inhibition in the two structures. Administration of SKF 38393, 3 days after priming, caused a power decrease in beta(1) frequency band of the cortex and striatum, which was more pronounced in apomorphine-primed as compared to drug-naive rats. The inhibitory effect of SKF 38393 was enhanced in rats primed with MK-801 plus apomorphine, particularly in the striatum. The results of this study suggest that long-term changes in the electrical activity of cortex and striatum after priming, might contribute to the development of the behavioral sensitization observed after priming. Development of priming might be related to the degree and cortical/striatal ratio of EEG power inhibition produced by dopamine agonists.

Interhemispheric EEG differences in olfactory bulbectomized rats with different cognitive abilities and brain beta-amyloid levels

Alterations in electroencephalogram (EEG) asymmetry and deficits in interhemispheric integration of information have been shown in patients with Alzheimers disease (AD). However, no direct evidence of an association between EEG asymmetry, morphological markers in the brain, and cognition was found either in AD patients or in AD models. In this study we used rats with bilateral olfactory bulbectomy (OBX) as one of the AD models and measured their learning/memory abilities, brain beta-amyloid levels and EEG spectra in symmetrical frontal and occipital cortices. One year after OBX or sham-surgery, the rats were tested with the Morris water paradigm and assigned to three groups: sham-operated rats, SO, and OBX rats with virtually normal, OBX(+), or abnormal, OBX(-), learning (memory) abilities. In OBX vs. SO, the theta EEG activity was enhanced to a higher extent in the right frontal cortex and in the left occipital cortex. This produced significant interhemispheric differences in the frontal cortex of the OBX(-) rats and in the occipital cortex of both OBX groups. The beta1 EEG asymmetry in SO was attenuated in OBX(+) and completely eliminated in OBX(-). OBX produced highly significant beta2 EEG decline in the right frontal cortex, with OBX(-)>OBX(+) rank order of strength. The beta-amyloid level, examined by post-mortem immunological DOT-analysis in the cortex-hippocampus samples, was about six-fold higher in OBX(-) than in SO, but significantly less (enhanced by 82% vs. SO) in OBX(+) than in OBX(-). The involvement of the brain mediatory systems in the observed EEG asymmetry differences is discussed.

Non-linearity in combined effects of ELF magnetic field and amphetamine on motor activity in rats.

The effects of short-term (15 min) pre-exposure of rats to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 6 mT) on their motor (locomotor and stereotypic) activity induced by d-amphetamine sulphate (AMPH) at different doses (0.5, 1.5 and 4.5mg/kg, i.p.) were studied in the open field test. In saline-treated rats both parameters of motor activity were unaffected by ELF-MF irradiation. The rats pre-exposed to ELF-MF and injected with the lowest dose of AMPH showed the same locomotor activity as control animals, while their stereotypic behaviour was significantly elevated. ELF-MF in combination with AMPH at higher doses significantly enhanced motor activity when compared with values obtained in both control and combined experiments with the lowest dose of the drug. However, only combined locomotor effect at the middle dose of AMPH was significantly greater than those observed in corresponding experiments with AMPH alone. These results demonstrate that acute short-term exposure to ELF-MF is able to modify a motor activity in dependence on the extent of AMPH-induced neurotransmitter imbalance.

Different effects of chronic exposure to ELF magnetic field on spontaneous and amphetamine-induced locomotor and stereotypic activities in rats

The effects of chronic (7 days) exposure to an extremely low frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) on spontaneous and amphetamine-induced (1.5mg/kg, i.p.) locomotor and stereotypic activities in adult rats were examined by open field test for 2h on exposure days 1, 3, and 7. After 1 day of exposure to ELF-MF, the spontaneous locomotor activity was increased clearly at the first hour of observation and significantly at the second one as compared to the corresponding values in other series with ELF-MF and sham-exposed animals. After 7 days of exposure to ELF-MF, an amphetamine enhancing effect on the locomotor activity was significantly reduced at the second hour of observation as compared to that in 1-day- and sham-exposed rats treated with amphetamine. In contrast to the locomotor activity, the amphetamine-induced stereotypic behaviour in 7-day pre-exposed rats was significantly reduced at the first hour versus sham-exposed rats. While at the second hour of observation this effect was significant as compared to 1- and 3-day exposed animals (but not sham-exposed rats). Our results indicate that an extremely low frequency magnetic field is able to affect differently two types of behaviour, which are dependent on both the time course of exposure and the imbalance in the brain mediatory systems.

Neuroprotective Effects of Hydrated Fullerene C60: Cortical and Hippocampal EEG Interplay in an Amyloid-Infused Rat Model of Alzheimer's Disease

We studied the effects of fullerene C60 nanoparticles, namely hydrated fullerene C60 (C60HyFn), on interrelations between EEG frequency spectra from the frontal cortex and the dorsal hippocampus (CA1) on an amyloid-β (Aβ) rat model of Alzheimers disease (AD). Infusion of Aβ1-42 protein (1.5 μl) into the CA1 region two weeks before EEG testing diminished hippocampal theta (3.8-8.4 Hz) predominance and eliminated cortical beta (12.9-26.2 Hz) predominance observed in baseline EEG of rats infused with saline (control) or with C60HyFn alone. In contrast, these Aβ1-42 effects were abolished in rats pretreated with C60HyFn, 30 min apart. Dopaminergic mediation in AD has been shown to be involved in neuronal plasticity and Aβ transformation in different ways. To clarify its role in the cortex-hippocampus interplay in the Aβ model of AD, we used peripheral injection of a dopamine agonist, apomorphine (APO), at a low dose (0.1 mg/kg). In rats infused with C60HyFn or Aβ1-42 alone, APO attenuated the cortical beta predominance, with immediate and delayed phases evident in the Aβ1-42-rats. Pretreatment with C60HyFn diminished the APO effect in the Aβ1-42-treated rats. Thus, we show that intrahippocampal injection of Aβ1-42 dramatically disrupts cortical versus hippocampal EEG interrelations and that pretreatment with the fullerene eliminates this abnormality. We suggest that some effects of C60HyFn may be mediated through presynaptic dopamine receptors and that water-soluble C60 fullerenes have a neuroprotective potential.

Natural scene statistics and the structure of orientation maps in the visual cortex

Visual activity after eye-opening influences feature map structure in primary visual cortex (V1). For instance, rearing cats in an environment of stripes of one orientation yields an over-representation of that orientation in V1. However, whether such changes also affect the higher-order statistics of orientation maps is unknown. A statistical bias of orientation maps in normally raised animals is that the probability of the angular difference in orientation preference between each pair of points in the cortex depends on the angle of the line joining those points relative to a fixed but arbitrary set of axes. Natural images show an analogous statistical bias; however, whether this drives the development of comparable structure in V1 is unknown. We examined these statistics for normal, stripe-reared and dark-reared cats, and found that the biases present were not consistently related to those present in the input, or to genetic relationships. We compared these results with two computational models of orientation map development, an analytical model and a Hebbian model. The analytical model failed to reproduce the experimentally observed statistics. In the Hebbian model, while orientation difference statistics could be strongly driven by the input, statistics similar to those seen in experimental maps arose only when symmetry breaking was allowed to occur spontaneously. These results suggest that these statistical biases of orientation maps arise primarily spontaneously, rather than being governed by either input statistics or genetic mechanisms.