Biomedical subjects

S Molotchnikoff

Publications and source records attributed to S Molotchnikoff.

At least 19 recordsLinked to original sources

PubMed2004

Effects of excitation and inactivation in area 17 on paired cells in area 18.

This investigation examines how neighboring neurons of area 18 react when area 17 inputs are excited or depressed. In anesthetized cats, area 18 responses to a sine-wave grating in the receptive field were analyzed, while a second grating was positioned in its periphery and responses were recorded in area 17. This latter site was also inactivated with GABA. A waveform template process sorted out at least two individual, neighboring cells with similar orientation preferences in area 18. These cells frequently displayed opposite reactions to stimulation and inactivation in area 17. Experiments suggest that nearby neurons belonging to the same functional domain in the visual cortex may simultaneously carry disparate information.

Action Potentials↗

PubMed2004

Contextual modulation of synchronization to random dots in the cat visual cortex.

Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8-12%) and/or moderate (25-50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion.

Animals↗

PubMed2003

Nitric oxide and its influence on oscillations of collicular responses in developing rats.

We investigated the influence of modulating NO synthesis on oscillatory components of ON and OFF evoked field potentials in developing rat superior colliculus. Nitric oxide (NO) is involved in neuronal transmission by adjusting neurotransmitter release in adults and in stabilizing synaptic connections in developing brains. NO synthesis was decreased by inhibiting nitric oxide synthase (NOS) with an acute microinjection of N-nitro-L-arginine methyl ester (L-NAME); whereas NO synthesis was augmented by an acute microinjection of L-arginine (L-ARG). The study is focused on rhythmic activity by analyzing fast Fourier transform (FFT). Collicular responses were recorded in anesthetized rats, at post-natal days (PND) 13-19 and adults. This time window was chosen because it is centered on eye opening. NO down- and upregulation resulted in a dual effect depending on age and response-type. NO synthesis inhibition decreased the magnitude of oscillations in ON responses in the youngest animals (PND13-PND14), whereas oscillations of frequencies higher than 20 Hz in OFF responses were increased in all age groups of developing rats. In adults NO downregulation increased oscillations in ON responses and decreased oscillations in OFF responses. L-arginine application produced effects opposite to those seen with L-NAME. Our data together with results reported in the literature suggest that the temporal patterns of the evoked activity are NO-dependent. This sculpting action of the evoked firing may play a role in the synchronization of action potentials in afferent axons which in turn contributes to synaptic stabilization.

Aging↗

PubMed2001

Comparative computations of spike synchronization in visual cortex of cats.

In recent years it has been proposed that synchronous activity between neurons is a putative mechanism to bind together various trigger features of an image. Thus the measure of synchronization becomes an important issue since it may be an electrophysiological sign of visual perception. This paper describes and compares six techniques of computing synchronization strength, that is, the central peak of a cross-correlogram. Data were obtained in anesthetized cats prepared for electrophysiological recordings in a conventional fashion. Results indicate that: (1) eye fits are misleading. Visual inspection of cross-correlograms, may be interesting if one needs to estimate approximately synchronization strength and the presence of oscillations in the cross-correlograms, however it may be misleading if one wants to compare different cross-correlograms; (2) regression analysis to compare one method against the others yields a relatively poor correlation suggesting that methods are not directly comparable; (3) the sensitivity of each computational method is unequal. The results may indicate that some functional connections are either under- or over-evaluated depending upon the strategy employed to measure synchronization.

Animals↗

PubMed2001

Modulation of the synchronization between cells in visual cortex by contextual targets.

It has been suggested that synchronization of action potentials encodes diverse features of a single image. However, properties of the synchronization, which occurs on a time scale of approximately 1-5 ms, are still poorly understood. We have tested the modulation of synchronization by manipulating the contextual targets introduced in the surround of the receptive field. Experiments were carried out on anaesthetized cats prepared for multiunit and single-cell recordings in area 17. Initially, a patch of sine-wave drifting grating was positioned over the overlapping receptive fields of several neurons. If this coherent motion produced a significant synchronization in cross-correlograms, contextual targets were added. The first contextual stimuli were two sine-wave patches placed above and below the central compound receptive field. Only the contrast of contextual targets changed. Results show that the larger the differential contrast the higher the synchronization. The second contextual stimulus was a lateral shift of a sine-wave patch. Data show that the wider the distance between the central and peripheral patches the better the synchronization. Furthermore, results suggest that the synchrony pattern computed by cross correlating multiunit recordings from two sites differs when the cross correlation is carried out between individual units belonging to each multiunit recording. Together with our previous results it appears that synchronization is stimulus dependent and its strength increases with larger disparities included in the whole stimulating image.

Action Potentials↗

PubMed2000

Stimuli outside the classical receptive field modulate the synchronization of action potentials between cells in visual cortex of cats.

It is proposed that various attributes of an image are bound neuronally when responsive units fire in synchrony. Our investigations describe the influences of the contextual stimuli upon the occurrence of synchronization, in anaesthetized cats. Once a significant synchronization was recorded in the cross-correlogram (XCRG) between evoked action potentials of two groups of neurons in response to a drifting sine-wave grating, additional gratings were positioned outside the compound receptive field. The synchronization strength was then measured in relation to the difference between the orientations of the central and peripheral gratings. In the majority of cases results indicate that the synchronization is facilitated with larger orientation disparities. Thus, our data support the notion that contrasting features of images facilitate synchrony of activity between neurons.

Action Potentials↗

PubMed2000

Cross-correlated and oscillatory visual responses of superficial-layer and tecto-reticular neurones in cat superior colliculus.

The present study examined, in the superior colliculus (SC) of anaesthetised cats, the functional connectivity between superficial-layer neurones (SLNs) and tectoreticular neurones (TRNs: collicular output cells). TRNs were antidromically identified by electrical stimulation of the predorsal bundle. The auto- and cross-correlation histograms of visual responses of both types of neurones were recorded and analysed. A delayed, sharp peak in cross-correlograms allowed us to verify whether SLN and TRN cells were coupled; in addition, oscillatory activities were compared to verify if rhythmic responses of SLN sites were transmitted to TRN sites. We found that oscillatory activity was rarely observed in spontaneous activity of superficial (1/74) and TRN sites (1/48). Moving light bars induced oscillation in 31% (23/74) of the superficial-layer and in 23% (11/48) of the TRN sites. The strength of the rhythmic responses was determined by specific ranges of stimulus velocity in 83% (19/23) and 64% (7/11) of oscillating SLN and TRN sites, respectively. Frequencies of oscillations ranged between 5 and 125 Hz and were confined, for 53% of the cells, to the 5-20 Hz band. Thus, the band-width of frequencies of the stimulus-related oscillations in the superior colliculus was broader than the gamma range. Analysis of cross-correlation histograms revealed a significant predominant peak with a mean delay of 2.7+/-0.9 ms in 46% (17/37) of SLN-TRN pairs. Most correlated SLN-TRN pairs (88%: 15/17) had superimposed receptive fields, suggesting they were functionally interconnected. However, individual oscillatory frequencies of correlated and oscillatory SLN and TRN cells were never the same (0/8). Together, these results suggest that the neurones in collicular superficial layer contact TRNs and, consequently, support the idea that the superficial layers contribute to collicular outputs producing eye- and head-orienting movements.

Animals↗

PubMed2000

Relationships between image structure and gamma oscillations and synchronization in visual cortex of cats.

The relationships between visual object configurations and interneuronal spike synchronization and gamma oscillations are examined in the present investigation. Cells were initially stimulated with moving, optimally oriented, single 20 degrees -long bars of light, centred on the compound receptive field of a pool of cortical neurons. When this kind of stimulus evoked intrinsic gamma oscillations and/or synchronization, we gradually fractured the original target. In addition, colinearity was ruptured by forming L- and T-shaped configurations. All fractures and discontinuities were introduced well outside the excitatory receptive field. Multiunit activity in the visual cortex (areas 17 and 18) was recorded in anaesthetized cats. Recording sites were separated by 0.4-1.2 mm. The data analysis indicates that gamma oscillations follow a rule by which unfractured bars yielded the highest S/N ratios. Synchronization strength, as revealed by the central peak in cross-correlograms, also seemed to depend upon stimulus configuration. However, the magnitude of the central peak failed to follow a consistent trend. For instance, the greatest magnitude of the central peak occurred for both colinear and orthogonal types of target. Our results support the notion that both gamma oscillations and neuronal synchronization are stimulus-dependent.

Action Potentials↗

PubMed2000

Cellular response to texture and form defined by motion in area 19 of the cat.

The present study examined the neuronal sensitivity in area 19 of the cat to a motion-defined bar and to texture. Sensitivity was tested in normal, lesioned (areas 17-18) and split-chiasm cats using a kinematogram, as well as a textured bar drifting on a uniform light background and a light bar drifting on a stationary textured background. Texture density was varied. The results indicate that almost all cells of area 19 recorded in the three groups of cats responded to a motion-defined bar or to its edges. Texture density influenced the responses in that the discharge rate increased as density decreased. However, the majority of cells were sensitive to the highest texture density kinematogram. Moreover, the neural responses of all cats were either independent of the density of the textured bar or background, or were modulated by it. These results show that cells in area 19 can signal the presence of a kinetic bar and that the density of either the textured bar, the background or both can influence figure-ground detection. The results are interpreted with respect to how various inputs influence the function of area 19.

Animals↗

PubMed2000

Regulation of endothelial nitric oxide synthase by PGD(2) in the developing choroid.

We investigated if prostaglandins might regulate the increased choroidal endothelial (e) nitric oxide synthase (NOS) expression in the perinate. Prostaglandins, eNOS mRNA, immunoreactive protein and activity, and nitrite [stable metabolite of nitric oxide (NO)] production were markedly higher in newborn (1 day old) than juvenile (6-8 wk old) pig choroid. Treatment of isolated newborn choroids with the prostaglandin synthase inhibitor ibuprofen for 24 h reduced eNOS mRNA and nitrite production to values in juveniles. This effect was equally observed with the PGD(2) receptor (DP) blocker BW A868C and was prevented by cotreatment with PGD(2) but not other prostaglandins; similar observations were made on NOS activity in vivo. PGD(2) also increased eNOS expression on choroids of juveniles, and this effect was blocked by BW A868C. The manifestation of this upregulation of eNOS by PGD(2) on the control of choroidal vasomotor response was tested by using NO-dependent vasorelaxants, ACh, bradykinin (Bk), and substance P (SP). ACh-, Bk-, and SP-elicited choroidal vasorelaxation was greater in saline-treated newborn than juvenile pigs. Ibuprofen (24 h) decreased ACh-, Bk-, and SP-evoked vasorelaxation in newborns, whereas PGD(2) increased that in juveniles and prevented the ibuprofen-induced attenuated relaxation in newborns; infusion of N(omega)-monomethyl-L-arginine in choroids of those animals treated with PGD(2) reversed the augmented vasorelaxation to ACh, Bk, and SP. Finally, PGD(2)-induced upregulation of NOS in the perinate was also reflected by curtailed choroidal blood flow autoregulatory response to increased perfusion pressure. In conclusion, PGD(2) exhibits a major role in upregulating eNOS expression and activity in the choroid, which in turn results in greater NO-mediated vasorelaxation; a new mechanism for eNOS regulation via DP is hereby disclosed. The relationship between PGD(2) and eNOS in the developing subject provides an explanation for the interactive role of these two factors in the absent choroidal blood flow autoregulation in the perinate.

Aging↗

PubMed1999

Pulvinar participates in synchronizing neural assemblies in the visual cortex, in cats.

It has been proposed that the perception of a coherent image necessitates two processes, that is, an ensemble of neurons which synchronizes discharges of individual cells and stimulus-specific gamma-band (gamma) neuronal oscillations which may serve as carrier signals for a temporal code. We tested the hypothesis that cortical gamma-oscillations and synchronization depend upon the interactions between the lateral posterior-pulvinar complex of the thalamus (LP-P) and visual cortex. Local reversible inactivation of the LP-P was achieved by pressure injections of gamma-aminobutyric acid (GABA). In the majority of cases the LP-P depression decreased the strength of the synchronization and oscillations. Also, the results demonstrate that the occurrence of stimulus-dependent oscillations and the synchronization of neuronal responses are two distinct processes and consequently they may occur or disappear independently of each other.

Animals↗

PubMed1999

Maturation of visual receptive field properties in the rat superior colliculus.

Visually responsive neurons were recorded in the superficial layers of rat superior colliculus from postnatal day 12 to 28. Receptive field properties such as size, type (ON, OFF, ON-OFF and motion sensitive) and direction selectivity were analyzed to disclose changes during maturation. Although some aspects of sensory properties are modified during development (latency, receptive field sizes, and proportions of receptive field types), a high level of sophistication is also present in young animals even before eyelid opening. For instance, direction selective and direction biased cells, which require complex synaptic relations, are already observed when the first light evoked responses emerge in the superior colliculus (P13), strongly suggesting that this property develops without visual experience. Furthermore, direction selectivity is present in the colliculus prior to the appearance of visually evoked activity in the cortex. This indicates that direction selectivity can not be attributable to incoming cortical afferents. This study provides the first direct evidence that, unlike the cat, the rat's cortico-tectal pathway is only weakly involved in the establishment of direction selectivity in collicular neurons.

Aging↗

PubMed1999

Developmental regulation of endothelial nitric oxide synthase in cerebral vessels of newborn pig by prostaglandin E(2).

We investigated whether prostaglandins regulate endothelial nitric oxide synthase (eNOS) in the pig cerebral vasculature during the neonatal period. Prostaglandins, eNOS mRNA, eNOS protein, and NO production were higher in cerebral microvessels of newborn (1 day old) than in those of adult (6- to 8-month-old) pigs. The treatment of isolated cerebral microvessels of newborn animals with ibuprofen for 24 h reduced eNOS mRNA and nitrite production to levels in the adult; this effect of ibuprofen was prevented by concurrent treatment with prostaglandin (PG)E(2) analog 16,16-dimethyl-PGE(2), nonselective PGE(2) receptor analog 11-deoxy PGE(1), and prostaglandin EP(3) receptor agonists sulprostone and M&B 28,767 but was not modified by PGI(2) analog carbaprostacyclin, PGD(2), and EP(1) receptor agonist 17-phenyl trinor PGE(2). Correspondingly, 16, 16-dimethyl-PGE(2) and M&B 28,767 increased eNOS mRNA expression of adult microvessels to values in the newborn. Data similar to those with isolated cerebral vessels were obtained through histochemical analysis (NADPH-diaphorase positivity) of brain from newborn animals treated in vivo with ibuprofen in combination or not with sulprostone. Furthermore, substance P-induced NO-mediated cerebral vasorelaxation was decreased to adult values through the treatment of newborn pigs with ibuprofen; this effect was prevented by concomitant treatment with sulprostone. It is concluded that PGE(2) regulates eNOS in newborn pig cerebral microvessels via EP(3) receptors; this may be physiologically required during normal neurovascular development.

Age Factors↗

PubMed1998

Influences of area 17 on neuronal activity of simple and complex cells of area 18 in cats.

To understand the influence of the ascending path linking area 17 to area 18 of visual cortices, experiments were carried out in which a small neuronal population of area 17 was inactivated with GABA, while unitary responses were recorded in area 18. In the latter, cells are identified as belonging to the simple or complex family according to their firing pattern evoked in response to sine-wave gratings scrolling through the receptive fields. Anesthetized cats were prepared for single-cell recordings. In area 17, a GABA-containing pipette was placed in superficial layers in order to inactivate reversibly a small neuronal population. Prior to blockade, the orientation tuning curves were obtained in both areas and the difference in optimal orientation between areas 17 and 18 was recorded. In area 18, cells were classified as simple or complex. The strategy was to study the reaction of neurons in area 18 prior to, during and after area 17 depression. In most simple cells, whenever the difference in orientation was in the iso-range, that is when the difference in optimal orientations of the injected site (in area 17) and of the neuron in area 18 was less than 30 degrees, the GABA application produced a decline of the evoked discharges, whereas GABA injection augmented the evoked firing rate when the difference was in the cross-range (>60 degrees). In contrast to simple cells, GABA depression enhanced the responses in the majority of complex cells with like orientations in both areas. When the difference between recording sites was in the cross-range, then area 17 depression produced weaker evoked firing. A tangential penetration of the injecting pipette, allowing injection of different orientation sites while testing the same unit in area 18, revealed that the latter could react with an enhancement or a decline of the responses as the injecting pipette shifted from iso (or cross) to cross (or iso) disparity in optimal orientations between areas 17 and 18. These results suggest that the path connecting area 17 to area 18 may be functionally discriminated on the basis of the orientation domain and cell types. In addition, our data suggest that the ascending visual streams are required to generate orientation specificity in area 18.

Animals↗

PubMed1998

PGE2, via EP3 receptors, regulates brain nitric oxide synthase in the perinatal period.

We tested the hypothesis that high prostaglandin levels during the perinatal period might regulate brain nitric oxide synthase (nNOS) expression. nNOS and cyclooxygenase (COX)-2 mRNAs were higher in brain cortex and the periventricular area of newborn rats and pigs compared with adult brain. Nitric oxide synthase activity was also 2. 5- to 4-fold higher in newborn than in adult brain. Administration of nonselective COX inhibitor ibuprofen or COX-2 inhibitor nimesulide every 8 h for 24 h to newborn rats and pigs reduced prostaglandin levels and caused comparable reductions in nNOS mRNA, protein, and activity to levels of adults; COX inhibitor-induced changes were prevented by cotreatment with PGE2 analog, 16, 16-dimethyl-PGE2, and agonist for the EP3 receptor of PGE2, sulprostone, but not by PGI2 analog carbaprostacyclin, PGD2, EP1 receptor agonist 17-phenyl trinor-PGE2, and EP2 agonist butaprost. Concordant observations were made in vitro and revealed that nNOS expression (detected by NADPH diaphorase reactivity) mostly present in neurons of the deeper cortical layers was reduced by COX inhibitor, and this effect was prevented by EP3 agonist. In conclusion, high levels of PGE2 in neonatal brain contribute to the increased expression of nNOS by acting on EP3 receptors; this positive interaction between PGE2 and nNOS might be required physiologically for normal brain development.

Aging↗

PubMed1997

Spatial frequency properties in area 18 during inactivation of area 17 in cats.

The aim of this investigation was to understand the functions of long horizontal connections projecting from area 17 to area 18 in cats. The animals were anesthetized and prepared for recording single-cell responses to sine-wave gratings in area 18. Neuronal activity was analyzed under three conditions: prior to, during, and after inactivation of a circumscribed region of area 17. The latter was depressed with micro-injections of GABA. Cells in both areas were in close retinotopic correspondence. Cells were classified as simple and complex types. Globally, simple cells were less affected than complex units, and those which were affected shifted their optimal spatial frequency to higher values. Complex neurons were more often influenced by the interruption of area 17 input. Namely, the peaks of the tuning curves were displaced on the x-axis to a new optimal spatial frequency. This effect was obtained by a dual change: a decline in the discharge strength to the optimal spatial frequency and an enhancement to nonoptimal spatial frequency. Contrast sensitivity function disclosed similar shifts of optimal spatial frequencies. Likewise bandwith, spatial resolution, high cutoff, and low cutoff were modified to a greater extent in complex cells. It appears that there is no relationship between areas 17/18 orientation difference and the modifications observed in tuning curves to spatial frequencies. The results suggest that neurons of area 18 may carry multiple-frequency channels and that area 17 facilitates the emergence of one particular spatial frequency.

Animals↗

PubMed1997

ON and OFF field potentials in the rat superior colliculus during development.

The present investigation is aimed at characterizing the development of ON and OFF visually evoked responses in the rat superior colliculus from postnatal day 13 (P13) to postnatal day 25. Depth profiles of field potentials reveal that ON and OFF long latency biphasic field potentials are already present when collicular cells are first responsive to light (P13). There is an inversion in the polarity of these responses as the electrode penetrates the collicular layers, suggesting a synaptic organization similar to the one found in adult animals. At P15, OFF field potentials begin to exhibit oscillatory activity. Local cobalt injections within the superior colliculus abolishes these OFF oscillations, suggesting a postsynaptic origin. Fast Fourier transform (FFT) analysis of the OFF field potentials demonstrates that oscillatory activity increases in frequency during development. This increase is thought to reflect the myelination and stabilization of synaptic connections that occur during this period. To our knowledge, this is the first report of OFF oscillatory responses in the superior colliculus.

Animals↗

PubMed1997

Characterization and regulation of prostaglandin E2 receptor and receptor-coupled functions in the choroidal vasculature of the pig during development.

Ontogenic changes in choroidal vascular prostaglandin E2 (PGE2) receptors (EP1, EP2, EP3, and EP4), changes in receptor-coupled functions, and the possible role of high perinatal prostaglandin levels in regulating expression and function of these receptors were studied. PGE2 receptors and their functions on choroidal tissues were characterized by radioligand binding; by measurements of second messengers to receptor stimulation; and by vasomotor response to EP1, EP2, EP3, and EP4 ligands on perfused choroidal vascular beds from saline- and ibuprofen-treated (40 mg/kg every 4 every 4 hours for 48 hours) newborn pigs and from adult animals. PGE2 as well as EP2- and EP4-attributed choroidal stimulation elicited greater vasorelaxation in the saline-treated newborn and was associated with higher nitrite (oxidation product of NO, N omega-nitro-L-arginine inhibitable) production than in adult tissues. In contrast, EP1 and EP3 stimulation caused significantly more constriction in the adult than in the newborn, and this was associated with increased production of inositol 1,4,5-trisphosphate (IP3) and greater reduction of cAMP synthesis in the adult. Maximum [3H]PGE2 binding was also higher (3-fold) in adult than in newborn tissues. Competition binding studies revealed that of the PGE2 receptors in the adult choroid, approximately 55% were of the EP1 subtype, 8% were EP2, 22% were EP3, and 15% were EP4. Newborn choroid contained approximately 33% each of EP1 and EP2 receptors, 20% of EP3, and 15% of EP4. Inhibition of endogenous prostaglandin synthesis for 48 hours with ibuprofen in newborns to attain levels found in the adult resulted in an upregulation of [3H]PGE2 binding, EP1- and EP3-mediated vasoconstriction, and increases and decreases in IP3 and cAMP production, respectively, in newborn tissues compared with adult tissues. On the other hand, ibuprofen treatment of newborns led to a decrease in PGE2- and EP4-mediated vasorelaxation and nitrite synthesis (associated with decreased expression of endothelial NO synthase) to levels observed in adults: EP2-elicited responses in newborns were not affected by ibuprofen. In conclusion, fewer EP1 receptors (associated with vasoconstriction), more EP2 receptors, and greater EP4-coupled NO production (coupled to vasorelaxation) seem to be responsible for the increased vasodilation to PGE2 in the newborn. The decrease in prostaglandin levels with age appears to cause, on one hand, upregulation of EP1 and EP3 receptors and receptor-coupled vasoconstriction and, on the other hand, decreased EP4-coupled NO synthesis and choroidal vasodilation. Altogether, these factors result in increased vasorelaxation to PGE2 in the newborn compared with the adult. These findings may help to explain the inability of the newborn to autoregulate choroidal blood flow.

Age Factors↗