The mammalian visual system is endowed with a nearly infinite capacity for the recognition of patterns and objects. To have acquired this capability the visual system must have solved what is a fundamentally combinatorial prob­ lem. Any given image consists of a collection of features, consisting of local contrast borders of luminance and wavelength, distributed across the visual field. For one to detect and recognize an object within a scene, the features comprising the object must be identified and segregated from those comprising other objects. This problem is inherently difficult to solve because of the combinatorial nature of visual images. To appreciate this point, consider a simple local feature such as a small vertically oriented line segment placed within a fixed location of the visual field. When combined with other line segments, this feature can form a nearly infinite number of geometrical objects. Any one of these objects may coexist with an equally large number of other

Visual feature integration and the temporal correlation hypothesis

The field topography of ERG components in man—I. The photopic luminance response

Identification and qualitative comparison of sensitivity analysis methods that have been used across various disciplines, and that merit consideration for application to food-safety risk assessment models, are presented in this article. Sensitivity analysis can help in identifying critical control points, prioritizing additional data collection or research, and verifying and validating a model. Ten sensitivity analysis methods, including four mathematical methods, five statistical methods, and one graphical method, are identified. The selected methods are compared on the basis of their applicability to different types of models, computational issues such as initial data requirement and complexity of their application, representation of the sensitivity, and the specific uses of these methods. Applications of these methods are illustrated with examples from various fields. No one method is clearly best for food-safety risk models. In general, use of two or more methods, preferably with dissimilar theoretical foundations, may be needed to increase confidence in the ranking of key inputs.

Identification and Review of Sensitivity Analysis Methods

How are the functions performed by one part of the nervous system integrated with those of another? This fundamental issue pervades virtually every aspect of brain function from sensory and cognitive processing to motor control. Yet from a physiological perspective we know very little about the neural mechanisms underlying the integration of distributed processes in the nervous system. Even the simplest of sensori-motor acts engages vast numbers of cells in many different parts of the brain. Such actions require coordination between a host of neural systems, each of which must carry out parallel computations involving large populations of interconnected neurons. It seems reasonable to assume that a mechanism or class of mechanisms has evolved to temporally coordinate the activity within and between subsystems of the central nervous system. For several reasons, neuronal rhythms have long been thought to play an important role in such coordination. Since the discovery of the Electroencephalogram (EEG) over 60 years ago it has been known that a number of structures in the mammalian brain engage in rhythmic activities. These patterned neuronal oscillations take many forms. They occur over a broad range of frequencies, and are present in a multitude of different systems in the b~ain, during a variety of different behavioral states. They are often the most salient aspect of observable electrical activity in the brain and typically encompass widespread regions of cerebral tissue. With the advent of new techniques of multielectrode recording and neural imaging, it is now within the realm of possibility 'to record from 100 single neurons simultaneously (Wilson and McNaughton, 1993), to optically measure the activity in a cortical area (Blasdel and Salama, 1986; T'so et al., 1990), or to noninvasively image the pattern of electric current flow in an alert human being performing a task (Pantev et al., 1991). These new techniques have revealed that spatially and temporally organized activity among distributed populations of cells often takes the form of synchronous rhythms. When combined with cellular neurophysiological and anatomical studies these findings provide new insights into the behavior and mechanisms controUing the coordination of activity in neuronal populations.

Synchronous oscillations in neuronal systems: mechanisms and functions.

Article de synthese a propos de l'existence d'une association entre la transmission par l'activation des recepteurs NMDA et les contacts explorateurs entre les neurones en developpement, pour definir une plasticite plus prononcee au niveau de certaines regions du cerveau, notamment les voies visuelles

Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways

1. Cholinergic drugs were infused into the retinal circulation of the rabbit while we analysed the receptive field properties of directionally sensitive retinal ganglion cells. Physostigmine eliminated the trigger feature, directional specificity, of both types (on-centre and on—off) of these cells. In this respect the action of physostigmine (an ACh potentiator) was very like that of picrotoxin (a GABA antagonist). Therefore, a detailed analysis of the receptive field properties of directionally sensitive ganglion cells was made to analyse the effects of physostigmine and picrotoxin.

2. Size specificity and radial grating inhibition were not abolished by physostigmine, but were often affected by picrotoxin. The optimal velocity in the preferred direction (as measured by maximum firing frequency) was not much changed by physostigmine, but was higher during infusion of picrotoxin. Infusion of nicotine, a depolarizing ACh agonist which increases the activity of retinal ganglion cells, revealed the presence of inhibition to movement in the null direction. The null direction response during picrotoxin started slightly later than this inhibition. The null direction response during physostigmine was weaker and started later still. Mecamylamine and dihydro-β-erythroidine, nicrotinic receptor antagonists, totally blocked the effect of physostigmine and reduced the control light response by about half.

3. From this analysis, it appears that on—off ACh release onto directionally sensitive cells provides a substantial excitation which, when potentiated by physostigmine, overcomes or outlasts the null direction GABA inhibition within the receptive field. The spatial extent of GABA inhibition is asymmetric to and larger than the spatial extent of ACh excitation. Similar pathways appear to be involved in both the on-centre and on—off directionally sensitive ganglion cells, yet the on-centre cell pathway may receive an additional input which suppresses the ACh excitation at light offset. Possible schemes for the cellular mechanism of directional sensitivity are discussed in light of these results and recent anatomical and pharmacological findings.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1982.sp014105

Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells.

1. Retinal ganglion cells were recorded extracellularly from the rabbit's eye in situ to study the effects of cholinergic drugs on receptive field properties. Physostigmine, an acetylcholinesterase inhibitor, and nicotine increased the spontaneous activity of nearly all retinal ganglion cell types. The effectiveness of physostigmine was roughly correlated with the neurone's inherent level of spontaneous activity. Brisk cells, having high rates of spontaneous firing, showed large increases in their maintained discharge, whereas sluggish cells, with few or no spontaneous spikes, showed small and sometimes transient increases in spontaneous activity during physostigmine.

2. The sensitivity of ganglion cells to spots of optimal size and position did not change substantially during the infusion of physostigmine. However, the responsiveness to light (number of spikes per stimulus above the spontaneous level) increased. This effect occurred with sluggish and more complex cells, rarely with brisk cells.

3. Another effect of physostigmine on sluggish and more complex cells was to make these cells `on—off'. The additional response to the inappropriate change in contrast had a long latency and lacked an initial transient burst.

4. Complex receptive field properties such as orientation sensitivity, radial grating inhibition, speed tuning and size specificity were also examined. These inhibitory properties were still present during infusion of physostigmine and, in most cases, the trigger feature of each cell type remained.

5. These results are consistent with pharmacological results on ACh release from the retina. There appear to be two types of release of ACh, having their most powerful influences on separate classes of cells. One release (transient), occurs at light onset and offset and acts primarily on sluggish and more complex ganglion cells; the other release (tonic) is not light-modulated and acts primarily on brisk cells. A wiring diagram for the ACh cells is suggested.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1982.sp014104

Effects of cholinergic drugs on receptive field properties of rabbit retinal ganglion cells.

We tested the effects of 6-hydroxydopamine (6-OHDA) on two forms of visual deprivation--monocular and directional deprivation. In normal kittens monocular deprivation leads to a change in the ocular dominance histogram recorded from the visual cortex, and directional deprivation leads to a change in the percentage of directionally sensitive cells responding to the appropriate direction of movement. 6-OHDA was infused into the occipital cortex prior to the peak of the critical period for the effects of visual deprivation. In agreement with the results of Kasamatsu et al. (Kasamatsu, T., and J. D. Pettigrew (1979) J. Comp. Neurol. 185: 139–162; Kasamatsu, T., J. D. Pettigrew, and M. Ary (1979) J. Comp. Neurol. 185: 163–182), suture of one eye (monocular deprivation) after the 6-OHDA treatment did not lead to a shift in ocular dominance in the area of striate cortex infused. Moreover, rearing kittens in an environment continually moving past them in one direction (directional deprivation) did not lead to a change in the percentage of cells preferring movement in that direction. In both rearing procedures the 6-OHDA did not make the cells in the cortex nonspecific, compared to cells recorded from the cortex of animals reared similarly but without infusion of 6-OHDA. Monocular and directional deprivation are forms of visual deprivation with different critical periods, probably involving different synapses. Therefore, the effect of 6-OHDA on visual deprivation is a general one, involving more than one kind of visual deprivation. In both cases 6-OHDA abolishes the plasticity of the visual cortex.

https://www.jneurosci.org/content/jneuro/3/5/907.full.pdf

Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex.

Synaptic drugs were superfused into turtle eyecup preparation while recording extracellularly from directionally sensitive (DS) retinal ganglion cells. As in previous experiments in intact rabbit retina, both picrotoxin (a GABA antagonist) and physostigmine [an acetylcholine (ACh) potentiator] reduced or eliminated the directional selectivity of these cells. These drug effects occurred at micromolar concentrations and were long lasting. Superfusion of ACh caused excitation, and GABA caused inhibition of the spike activity of these DS cells. In some experiments, the ganglion cell was isolated from its presynaptic inputs by perfusing with a low-Ca2+/EGTA perfusate, which blocked synaptic transmission but did not suppress spike firing. During this synaptic block, ACh still caused spontaneous spike firing, and GABA was able to suppress the ACh-induced spike activity. Strychnine slightly increased the spontaneous activity of DS ganglion cells and reduced their response to light. Glycine and taurine were equally effective in totally suppressing spike activity, and strychnine blocked this inhibition by both agents. However, these inhibitory effects may be transynaptic because glycine did not suppress ACh-induced excitation during synaptic block. Superfusion of micromolar concentrations of methionine enkephalin and [D-Ala2]methionine enkephalinamide occasionally caused small increases in the light responses of DS cells, whereas naloxone, a broad-spectrum opiate antagonist, moderately decreased light responsiveness. Because naloxone had no effect on these cell's directional tuning, the opiate system is probably not involved in the mechanism of directional sensitivity. Based on the effects of these transmitter candidates and their antagonists, a possible site fo DS subunits may be the ACh and GABA receptors on the membrane of DS ganglion cells. ACh provides light-evoked excitation that may, when potentiated by physostigmine, overcome asymmetric GABA inhibition. Although the role of glycine in directional sensitivity is small, it may be responsible for regulating presynaptic excitatory pathways leading to the DS ganglion cells.

Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells.

1. The spike responses of 105 cells to visual-stimulus movement were analyzed in the turtle's basal optic nucleus (BON) in vitro in the absence of the telencephalon. All cells were direction sensitive (DS) and were driven solely by stimulation of the contralateral eye. These cells had large receptive fields and had vigorous responses to moving, textured patterns. Small moving spots generated only weak responses from these cells, as did the onset or offset of diffuse light flashes. 2. The direction tuning of BON cells was quite broad with most back and forth responses being DS. In fact, for 86% of the cells, there were seven to nine axes (out of 9 total, in 20 degrees increments) for which response to movement in one direction was at least twice that for the opposite direction. In instances where spontaneous activity was relatively high, a suppression of that spike firing was evident when the stimulus moved in directions opposite to preferred stimulus directions. 3. Cells preferring many different directions are found in the BON. More cells preferred inferior-temporal directed motion (49%), compared to superior-temporal (35%) and nasal stimuli (13%). 4. BON cells remained DS over 3 log units of velocity, with their strongest responses between 1 and 50 degrees/s. Responses were often non-DS for stimuli moving slower than 0.1 degrees/s. 5. The receptive fields of BON cells were large and occupied different parts of the retina. When different subregions of a receptive field were stimulated, the cell's directional tuning always remained the same as the full field direction tuning. 6. Thus, BON cells seem well-suited for the analysis of global, visual-field motion in any direction, performed by the accessory optic system. Other brain stem pathways necessary for optokinetic reflexes can be elucidated with the use of this whole-brain, eyes-attached in vitro preparation.

Michael Ariel

Papers

Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells.

Effects of cholinergic drugs on receptive field properties of rabbit retinal ganglion cells.

Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex.

Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells.

Visual-response properties of neurons in turtle basal optic nucleus in vitro