Effects of ketamine on orientation selectivity and variability of neuronal responses in primary visual cortex.

The plasticity of the adult brain is one of the most highly evolving areas of recent neuroscience research. It has been acknowledged that the visual cortex in adulthood can adapt and restructure the neuronal connections in response to a sensory experience or to an imposed input such as in adaptation or ocular deprivation protocols. In order to understand the basic cellular mechanisms of plasticity in the primary visual cortex (V1), we examined the effects of ketamine, a non-competitive, glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, on the orientation of cortical cells by measuring their response variability and the Gaussian tuning curves in adult anesthetised mouse and cat. Neurons were recorded extracellularly using glass electrodes. The ketamine was applied locally by placing a custom-cut filter paper (1x1mm) soaked in ketamine solution (10 mg/ml) on the cortical surface next the site of the recording tip, in both species. Our results show that the local and acute exposure of ketamine on V1 changes the preferred orientation of the visual neurons established during the critical period of development. Furthermore, ketamine also leads to a decrease in the orientation selectivity (measured by orientation selectivity index, OSI) and the variability of neuronal evoked responses (measured by Fano factor), but does not affect spontaneous activity. These results suggest that ketamine induces plasticity in V1 neurons that might be operated by a different pathway than that of NMDARs.

Adaptation changes the spatial frequency tuning of adult cat visual cortex neurons.

The modular layout of striate cortex is arguably a hallmark of all cortical organization. Neurons of a given module or domain respond optimally to very few specific properties, such as orientation or direction. However, it is possible, under appropriate conditions, to compel a neuron to respond preferentially to a different optimal property. In anesthetized cats, prepared for electrophysiological recordings in the visual cortex, we applied a spatial frequency (SF) that differs (by 0.25-3.0 octaves) from the optimal one for 7-13 min without interruption. This application shifted the tuning curve of the cell mainly in the direction of the imposed SF. Indeed, results indicate an attractive push occurring more frequently (50%) than a repulsive (30%) shift in cortical cells. The increase of responsivity is band-limited and is around the imposed SF, while flanked responses remained unmodified in all conditions. We hypothesize that the observed reversible plasticity is obtained by a modulation of the balance between the strengths of the respective synaptic inputs. These changes in preferred original optimal spatial frequencies may allow a dynamic reaction of cortex to a new environment and particularly to ''zoom'' cellular activity toward persistent stimuli in spite of the tuning inherited from genetic programming of response properties and environmental conditions during critical periods in new born animals.

Modulation of functional connectivity following visual adaptation: homeostasis in V1.

Sensory neurons exhibit remarkable adaptability in acquiring new optimal selectivity to unfamiliar features when a new stimulus becomes prevalent in the environment. In conventionally prepared adult anesthetized cats, we used visual adaptation to change the preferred orientation selectivity in V1 neurons. Cortical circuits are dominated by complex and intricate connections between neurons. Cross-correlation of cellular spike-trains discloses the putative functional connection between two neurons. We sought to investigate changes in these links following a 12 min uninterrupted application of a specific, usually non-preferred, orientation. We report that visual adaptation, mimicking training, modulates the magnitude of crosscorrelograms suggesting that the strength of inter-neuronal relationships is modified. While individual cell-pairs exhibit changes in their response correlation strength, the average correlation of the recorded cell cluster remains unchanged. Hence, visual adaptation induces plastic changes that impact the connectivity between neurons.

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.

Visually-triggered oscillations in the cat lateral posterior-pulvinar complex.

The so-called 40 Hz oscillations are found at almost all stages of visual processing are thought to play a critical role in perception. The goal of this investigation was to look at the presence of stimulus-specific oscillations in the lateral posterior-pulvinar complex of the thalampus (LP-P) for which the oscillations were still not described. Rhythmic patterns in multiunit LP-P activity of anaesthetized cats were revealed in 14% of recording sites. With the exception of one pool of LP-P cells that exhibited stimulus-dependent rhythmic activity approximately 130 Hz, 90% of autocorrelograms were modulated between 18 and 74 Hz with dominant frequencies of 20-33 Hz. Since the LP-P sends efferents to the visual cortex it seems possible that oscillations from the LP-P can propagate to cortical neurones, especially to complex cells, for which similar dominant frequencies were noted by previous investigators.

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.

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.

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.

Modulations of collicular visual responses by acoustic stimuli in rabbits.

This study analyzes the influences of an acoustic stimulus upon neuronal light responses of superficial layers of the superior colliculus in anesthetized and paralyzed rabbits. The results have revealed that even if visually-responsive cells fail to be excited by sound, the latter is still capable of modifying light-evoked discharge. The influence may be "short-term" (the discharge rate recovers within 500 ms) or it may be "long-term" (the firing rate remains modified for several seconds). This audio-visual interaction depends upon several factors: the time of occurrence of both stimuli, the physical aspects of the visual target, the relative positions of the speaker and the visual receptive field, and finally, the sensitivity of the unit to movement direction. Data indicates that cells of the most dorsal (hence visual) layers of the superior colliculus are influenced by sound. It is concluded that the colliculus may use the sound as an additional cue to orientate the animal. Also, collicular cells could "memorize" for several seconds various features present in the environment.

Lateral geniculate cell responses to electrical stimulation of the retina.

Electrical stimulation of the retina evokes at the optic tract level rhythmic bursts of activity whose temporal structure is predictable from the polarity of the stimulation and the receptive field type. The reaction of lateral geniculate units to this input was studied in fast and slow relay cells as well as in interneurons. The results revealed that fast relaty cells presented a response whose temporal structure remained essentially unmodified in comparison to that observed at the optic tract level: that both anodal and cathodal polarities produced rythmic pattern of excitation the latency of which depended upon receptive field type and polarity applied. In slow relay cells and interneurons responses with equal latencies could be evoked for both polarities. Following cortical depression with 3 M KCl the latency of first bursts was unaffected in relay cells, while about one third of interneurons showed a temporal pattern which was similar to that recorded at the optic tract level after the treatment. This suggests that both ON and OFF retinal networks converge upon one geniculate slow P cell and interneuron, whereas fast relay cells are mostly driven by one of the two systems. Furthermore this convergence may be achieved through visual cortex in some units.

Susceptibility of neurons in area 18a to blockade of area 17 in rats.

The present investigation is aimed at studying the influence of the striate cortex (area 17 or V1) upon responses of area 18a. Electrical activity was recorded from neurons in area 18a through glass micropipettes. At the same time lidocaine hydrochloride was injected in the same retinotopic register of area 17. Forty eight cells were tested to diffuse stroboscopic flashes and to localized stationary or moving slits in the receptive field. In addition, orientation selectivity was analyzed in 15 units. Blockade of area 17 produced the following results: discharges to stroboscopic light were unaltered while responses to stationary, localized targets were diminished in about half of the cells. Fifty percent of movement evoked responses were decreased. The orientation properties were particularly sensitive to blockade of area 17. Out of 15 units, 13 had their orientation tuning curves altered by the treatment. These results seem to suggest that the degree of trigger feature complexity depends upon lateral interactions between areas V1 and V2.

Influences of cortico-pretectal fibers on responses of rat pretectal neurons.

Responses of pretectal cells were studied following cortical excitation and inactivation in anesthetized rats. The visual cortex was excited electrically and by a topical application of strychnine while it was inactivated by a reversible cryoblockade. In a few experiments the superior colliculus was locally depressed by microinjections of lidocaine hydrochloride. Results showed a large spectrum of response latencies to electrical stimulations of the optic chiasm and visual cortex, and a significant correlation between responses to both sites of stimulation. It appears that pretectal cell responses strongly depend upon corticofugal impulses, as the disruption of the latter results in a profound decline of pretectal discharges. The suppressed-by-light cells were the most affected by a cryoblockade while the ON-tonic units were the least affected. The same types of cells were affected at the retinal level by cortical blockade.

Influence of the visual cortex upon receptive field organization of lateral geniculate cells in rabbits.

In anesthetized rabbits, the receptive fields of lateral geniculate cells were mapped prior to and following the interruption of the corticogeniculate feed-back. Visual cortex (V.C.) was depressed by a focal application of 3 M KCl. The responsiveness of the V.C. was verified by monitoring the visually evoked potentials. In off- and on-center cells, the surround excitatory responses were remarkably reduced and even fully abolished in most units. In contrast, the center excitation remained unmodified. These effects were reversible. In some on-center units the center response had also decreased, and was replaced by an evoked inhibitory response. Relay cells and interneurons which yielded on and off responses over the entire area of the receptive field exhibited a loss of only one of the evoked discharges. It is concluded that the V.C. exerts mostly a specific desinhibitory action upon the geniculate network. This action affects either the center or the surround responses differentially. The results are compared with those obtained from cats.

Influence of a local inactivation in the superior colliculus on lateral geniculate responses in rabbits.

The influence of the superficial layers of the superior colliculus (SC) on responses of the lateral geniculate nucleus was studied in anesthetized and paralyzed rabbits. Fifty to one hundred nanoliters of inactivating drugs were injected through a micropipette positioned in the SC in register with the geniculate cells. The latter were tested with discrete moving and stationary targets presented in random sequences. Results revealed that the SC exerted a dual facilitative (n = 19) and inhibitory (n = 25) influence. The latter segment of the response pattern was modified while the initial portion remained unchanged. In some cases differential effects were observed, that is, the responses to one particular stimulus were more affected than responses to other modalities. However, in the majority of cells it was the on-off responses which were most affected. These findings point toward complex influences of the SC upon geniculate responses in rabbits. This complexity is also supported by findings that in cats the colliculo-geniculate synapses are of various types.

Stimulus-dependent oscillations in the cat visual cortex: differences between bar and grating stimuli.

We have investigated the dependence of cortical oscillations on the type of visual stimulus. Single unit recordings were performed in areas 17 and 18 of the cat visual cortex. Among 217 cortical neurons oscillations in the frequency range of 22-102 Hz were found in 29 cells (13%). The proportion of oscillating cells was higher (16%) if both bar and grating stimuli were used to stimulate cortical neurons. It was found that gratings are more effective than bars in triggering oscillatory patterns in cortical cells. Among 21 oscillating cells which were stimulated with both bar and grating stimuli, oscillations evoked with gratings were found in 17 neurons (81%) while oscillations evoked with bar stimuli were triggered in 7 cells (33%). The distributions of oscillation frequencies were statistically different for oscillations evoked with bars and gratings. Frequencies of oscillations evoked with bars were in the lower and higher range than frequencies of oscillations evoked with gratings. In 3 cells (14%), rhythmic patterns could be evoked with both bar and grating stimuli. However, the oscillations were of different frequencies. No significant correlation was found between the strength of oscillations and firing rate of cortical neurons. Both simple and complex cells manifested the same dependence on stimulus type. However, complex cells mostly exhibited oscillations in the lower frequency range while simple cells did so when neurons were stimulated with bars. The results suggest that various classes of visual stimuli can be coded by a temporal pattern of cortical responses.

Functional development of the neonatal rat retinotectal pathway.

Electrophysiological activity in the neonatal rat superior colliculus was recorded to measure neuronal and synaptic activity, and, therefore, functional development. Neonatal rat pups were studied from five days to two weeks of age. The earliest activity in the superior colliculus were spontaneous discharges at a frequency of one unit per animal on postnatal day 6 (P6). Spontaneously discharging units were more numerous at P8, and the number peaked on P10. The first clear response to optic nerve stimulation was seen on P10, with relatively long and variable latencies. By P14, electrically evoked responses had much shorter latencies. The results are in line with the first response to light flash in the superior colliculus at P12/13. The evidence suggests that functional development of the rat retinotectal pathway begins at the end of the first week after birth, and that much of the functional maturation occurs mainly during the second week after birth.

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.

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.

The conduction velocity and central projections of retinofugal fibers in the rabbit.

IN anesthetized and paralyzed rabbits, action potentials were elicited antidromically following electrical stimulation of optic tract terminals at the geniculate level (LGN). The conduction velocity spectrum extended from 7 m.s-1 to 34 m.s-1. The distribution of conduction velocities indicated four major modes at 10, 18, 22 and 26 m.s-1. Antidromic compound action potentials exhibited good correlation between the conduction latency and the major modes of the distribution histogram. These results suggest that the rabbit optic tract is composed of four classes of fibers varying in their conduction velocities. The central projections of retinofugal axons were studied with electrical stimulations of the Superior Colliculus (CS) and the LGN while recording from the same optic tract fiber. Antidromic spikes could be elicited from all conduction velocity groups and 71% of axons responded to both sites of stimulation. This finding indicates that most retinofugal fibers branch to and innervate both CS and LGN. Further, there is a tendency for fast-conducting axons to have their receptive fields located eccentrically relative to the optic axis of the eye.

Generation of end-inhibition in striate neurons in rabbits.

Eighty-six rabbit striate neurons were tested with lateral microinjection of lidocaine, GABA or bicuculline. Seven of the neurons expressed different levels of end-inhibition. We examined these end-stopping units by injection of lidocaine or bicuculline in adjacent areas in order to determine if a lateral cortical mechanism is underlying end-inhibition in rabbits as it has been proposed in cats. Microinjection of lidocaine resulted in an attenuation of the end-inhibition strength. Application of bicuculline had the opposite effect; the end-inhibition was reinforced. We suggest that as observed in cats, in rabbits end-inhibition is mediated through horizontal cortical connections which implies a postsynaptic inhibitory input to the end-stopping cell.