Noradrenergic modulation of functional selectivity in the cat visual cortex: an in vivo extracellular and intracellular study.

In vitro intracellular studies have shown that norepinephrine modulates cellular excitability and synaptic transmission in the cortex. Based on these effects, norepinephrine has been proposed to enhance the signal-to-noise ratio and to improve functional selectivity by potentiating strong synaptic responses and reducing weak ones. Here we have studied the functional effects of iontophoretic applications of norepinephrine during in vivo extracellular and intracellular recordings from neurons of the primary visual cortex of kittens and adult cats. Analysis of extracellular data concentrated on norepinephrine-induced changes in spontaneous and evoked activities, in signal-to-noise ratio, and in orientation and direction selectivity. Analysis of the intracellular data concentrated on actions of norepinephrine on spike firing accommodation, which has been shown to be reduced by norepinephrine in vitro, and on synaptic responses. Application of norepinephrine resulted in a depression of both spontaneous and evoked spiking activity. However, no systematic change in signal-to-noise ratio was observed. The suppressive effect of norepinephrine was exerted with no significant sharpening of direction or orientation selectivity tuning. The overall reduction in visual activity by norepinephrine affected the orientation tuning curves in a way compatible with a divisive effect, that is a normalization or gain control with no change in tuning width. Norepinephrine applied during intracellular recordings reduced the visually evoked depolarizing potentials whereas no change in the responsiveness of the cell to current-induced depolarizations was observed. In conditions of optimal visual stimulation which produced large depolarizations of several hundreds of milliseconds and sustained repetitive firing comparable to that obtained by direct current injection, we were unable to observe a facilitation of the evoked responses by norepinephrine as it would be expected from the well-documented increase in excitability induced by norepinephrine in vitro. In conclusion, from these results we suggest that norepinephrine released in the primary visual cortex primarily reduces the level of cortical activation by afferent signals, without affecting the cortical functional selectivity nor increasing the signal-to-noise ratio.

The visual cortical association field: a Gestalt concept or a psychophysiological entity?

The receptive field of a visual neurone is classically defined as the region of space (or retina) where a visual stimulus evokes a change in its firing activity. Intracellular recordings in cat area 17 show that the visually evoked synaptic integration field extends over a much larger area than that established on the basis of spike activity. Synaptic depolarizing (dominant excitation) responses decrease in strength for stimuli that are flashed at increasing distances away from the centre of the discharge field, while their onset latency increases. A detailed spatio-temporal analysis of these electrophysiological data shows that subthreshold synaptic responses observed in the 'silent' surround of cortical receptive fields result from the intracortical spread of activation waves carried by slowly conducting horizontal axons within primary visual cortex. They also predict that a perceptual facilitation may occur when feedforward activation produced by the motion signal in the retina travels in phase in the primary visual cortex with the visually induced spread of horizontal activation. A psychophysical correlate has been obtained in humans, showing that apparent motion produced by a sequence of co-linear Gabor patches, known to preferentially activate V1 orientation selective cells, are perceived by human observers as much faster than non co-linear sequences of the same physical speed.

Horizontal propagation of visual activity in the synaptic integration field of area 17 neurons.

The receptive field of a visual neuron is classically defined as the region of space (or retina) where a visual stimulus evokes a change in its firing activity. At the cortical level, a challenging issue concerns the roles of feedforward, local recurrent, intracortical, and cortico-cortical feedback connectivity in receptive field properties. Intracellular recordings in cat area 17 showed that the visually evoked synaptic integration field extends over a much larger area than that established on the basis of spike activity. Synaptic depolarizing responses to stimuli flashed at increasing distances from the center of the receptive field decreased in strength, whereas their onset latency increased. These findings suggest that subthreshold responses in the unresponsive region surrounding the classical discharge field result from the integration of visual activation waves spread by slowly conducting horizontal axons within primary visual cortex.

Synaptic origin and stimulus dependency of neuronal oscillatory activity in the primary visual cortex of the cat.

1. We have studied the oscillatory activity of single neurons (91 recorded extracellularly and 76 intracellularly) in the primary visual cortex of cats and kittens to characterize its origins and its stimulus dependency. A new method for the detection of oscillations was developed in order to maximize the range of detectable frequencies in both types of recordings. Three types of activity were examined: spontaneous background activity, responses to intracellular current steps and visual responses. 2. During spontaneous activity, persistent oscillatory activity was very rare in both types of recordings. However, when intracellular records were made using KCl-filled micropipettes, spontaneous activity appeared rhythmic and contained repeated depolarizing events at a variety of frequencies, suggestive of tonic periodic inhibitory input normally masked at resting potential. 3. Patterns of firing activity in response to intracellular current steps allowed us to classify neurons as regular spiking, intrinsically bursting, and fast-spiking types, as described in vitro. In the case of rhythmically firing cells, the spike frequency increased with the amount of injected current. Subthreshold current-induced oscillations were rarely observed (2 out of 76 cells). 4. Visual stimulation elicited oscillations in one-third of the neurons (55 out of 167), predominantly in the 7-20 Hz frequency range in 93% of the cases. Rhythmicity was observed in both simple and complex cells, and appeared to be more prominent at 5 and 6 weeks of age. 5. Intracellular recordings in bridge mode and voltage clamp revealed that visually evoked oscillations were driven by synaptic activity and did not depend primarily on the intrinsic properties of recorded neurons. Hyperpolarizing the membrane led to an increase in the size of the rhythmic depolarizing events without a change in frequency. In voltage-clamped cells, current responses showed large oscillations at the same frequency as in bridge mode, independently of the actual value of the holding potential. 6. In fourteen intracellularly recorded neurons, oscillations consisted of excitatory events that could be superimposed on a depolarizing or a hyperpolarizing slow wave. In two other neurons, visual responses consisted of excitatory and inhibitory events, alternating with a constant phase shift. 7. Drifting bars were much more efficient in evoking oscillatory responses than flashed bars. Except in three cells, the frequency of the oscillation did not depend on the physical characteristics of the stimulus that were tested (contrast, orientation, direction, ocularity and position in the receptive field). No significant correlation was found between the intensity of the visual response and the strength of the rhythmic component. 8. Although it cannot be excluded that the dominant frequency of oscillations might be related to the type of anaesthetics used, no correlation was found between local EEG and the oscillatory activity elicited by visual stimulation. 9. We conclude that the oscillations observed in the present work are generated by synaptic activity. It is likely that they represent an important mode of transmission in sensory processing, resulting from periodic packets of synchronized activity propagated across recurrent circuits. Their relevance to perceptual binding is further discussed.

Synaptic integration fields and associative plasticity of visual cortical cells in vivo.

Two major constraints in connectivity decide the spatial extent of visual cortical receptive fields, both during development and adult functioning: 1) feedforward input, extrinsic to visual cortex, is organized in an orderly projection to form a point-to-point mapping of the retina onto the cortical mantle and constitutes the core of the minimal discharge field (MDF) after amplification by local intracortical circuits; and 2) a second type of connectivity consists of long distance horizontal intracortical connections which are thought to favor the binding of local visual operations occurring simultaneously in different parts of the visual field. We review here possible factors, intrinsic to the considered cortical cell, that may control the effectiveness of post-synaptic integration. Their expression during sensory recognition could depend on the spatio-temporal distribution of active inputs onto the target cell dendrite and on their interplay with non-linearities of the membrane properties. On the basis of intracellular recordings in cat area, 17, we have observed that peripheral responses (excitatory and inhibitory) could be boosted by coincident postsynaptic depolarization. This effect is lost if the response and the postsynaptic depolarization are mismatched by 1,000 ms, suggesting that temporal correlation of central and peripheral responses could regulate in a non-linear manner the gain of center-surround interactions. This temporal selectivity is compatible with up-regulation of composite potentials by the transient voltage-dependent activation of slowly inactivating conductances in visual cortical neurons. A direct consequence of these different considerations is that the receptive field (RF) of neurons in visual pathways should not be considered as a static hardwired window probing the outer environment, but as an active filter which may continuously adapt and be updated as a function of global context and past experience.

An intracellular study of space and time representation in primary visual cortical receptive fields.

In contrast with previous knowledge based on extracellular recordings, the recent development of intracellular techniques in vivo (sharp electrode or 'blind patch') ideally allows experimenters to analyze and dissect the contribution of feedforward and lateral connectivity in the functional expression of a synaptic 'integration field'. We will present recent data which demonstrate that the visual receptive field of cortical neurons described at the level of subthreshold synaptic events extends over much larger regions of the visual field than previously thought, and that the capacity of cells to amplify subthreshold responses depends on the immediate past history of their membrane potential. Our data suggest that visual cortical receptive fields should not be considered as a fixed entity but more as a dynamic field of integration and association. Two types of dynamics can be argued for: 1) the spatial structure of the minimal discharge field (defined by suprathreshold activation of the cell) can be profoundly reorganized at least during development and most probably during selective phases of learning under the control of activity-dependent mechanisms. Adaptive changes in visual responses are thought to reflect long-lasting potentiation and/or depression of synaptic efficacies conveying ON- and OFF-center information; and 2) during sensory processing, reconfiguration of synaptic weights may be achieved on a much faster time-scale and linked to nor-linear properties of the postsynaptic membrane as well as that of recruited networks. Association of information available in the central part of the receptive field (RF) and of input coming from the reputedly 'unresponsive' regions surrounding it, or arising simultaneously from different parts of the visual field, might be suppressive in certain cases and capable of boosting hidden responses in other cases, depending on the global stimulus configuration.

Synaptic origin of rhythmic visually evoked activity in kitten area 17 neurones.

Rhythmic patterns in neuronal activity in response to moving stimuli were observed in 28% of cells recorded extracellularly or intracellularly in area 17 of 4-16 week old anaesthetized and paralysed kittens. In both recording modes, oscillation frequencies ranged between 7 and 71 Hz, and were confined for 88% of cells in the 7-20 Hz band of the spectrum. A comparative study of firing autocorrelograms) and subthreshold activity (autocorrelation functions) indicates that the regularity of discharge stemmed from visually evoked oscillations of membrane potential at the same frequency. These oscillations are shown to result from extrinsic excitatory activity, since their amplitude, but not their frequency, depends on the resting membrane potential. The dependency on stimulus configuration supports the hypothesis that oscillations in neuronal output are dictated by periodic activity in afferent circuits selectively recruited by different attributes of the visual input which are not exclusively processed at the cortical level.