Transient intra-areal axons in developing cat visual cortex

Transient axons reaching the medialmost part of area 17 were demonstrated with anterogradely transported biocytin injected in the dorsal part of the lateral gyrus in kittens during the first and second postnatal weeks. The axons decreased in number during the third postnatal week and were only exceptionally found thereafter. Computer-aided reconstructions from serial sections demonstrated axons with different degrees of complexity. The most complex ones were found at postnatal days 7-9 and were characterized by multiple branches terminating with growth cones in the white matter. Characteristically, endings of axons that entered the cortex remained confined to the infragranular layers V and VI. A few axons entered the supragranular layers. Transient axons terminated with different endings, which may indicate different stages of maturation. A few, possibly permanent, axons were still found in the medial part of area 17 at the end of the first, and during the second postnatal months; they arborized widely in the infragranular layers, and modestly or not at all supragranularly.     

The role of visual experience in the development of columns in cat visual cortex

The role of experience in the development of the cerebral cortex has long been controversial. Patterned visual experience in the cat begins when the eyes open about a week after birth. Cortical maps for orientation and ocular dominance in the primary visual cortex of cats were found to be present by 2 weeks. Early pattern vision appeared unimportant because these cortical maps developed identically until nearly 3 weeks of age, whether or not the eyes were open. The na?ve maps were powerfully dominated by the contralateral eye, and experience was needed for responses to the other eye to become strong, a process unlikely to be strictly Hebbian. With continued visual deprivation, responses to both eyes deteriorated, with a time course parallel to the well-known critical period of cortical plasticity. The basic structure of cortical maps is therefore innate, but experience is essential for specific features of these maps, as well as for maintaining the responsiveness and selectivity of cortical neurons.     

Stimulus-dependent neuronal oscillations and local synchronization in striate cortex of the alert cat

Neuronal responses to visual stimuli that are correlated on a millisecond time scale are well documented in several areas of the mammalian visual cortex. This coherent activity often takes the form of synchronous rhythmic discharges ranging in frequency from 20 to 70 Hz. We performed experiments to determine the incidence and properties of this rhythmic activity in the striate cortex of alert cats and to compare this activity to similar data collected in the striate cortex of anesthetized cats. The results demonstrate that optimal visual stimuli evoke robust, locally synchronous, 20-70 Hz oscillatory responses in the striate cortex of cats that are fully alert and performing a visual fixation task. The oscillatory activity is stimulus dependent, largely absent during periods of spontaneous activity, and shows a systematic increase in frequency with increasing stimulus velocity. Thus, the synchronous oscillatory activity observed in this and earlier studies cannot be explained as an artifact of anesthesia nor as a phenomenon that occurs independent of visual stimulation. Rather, it is a robust process that is present in the alert state and is dependent on the presence and specific properties of visual stimuli.     

Down-regulation of beta-adrenergic receptor following long-term monocular deprivation in cat visual cortex

To examine how adrenergic receptor binding is modified by experimental manipulation of sensory afferent, we carried out binding experiments (membrane fraction and in vitro autoradiography) for both alpha 2- and beta-adrenergic receptors in the brain of cats which had been deprived of vision in one eye. In the cerebral cortex of control animals, beta-adrenergic receptor (beta-AR) binding was found to be higher in the occipital regions than in other regions, while alpha 2-AR binding was relatively uniform. Monocular deprivation throughout the postnatal sensitive period (1-7 month of age) significantly decreased beta-AR binding in the visual cortex and lateral geniculate nucleus. Scatchard plot analysis in the visual cortex showed ca. 50% reduction in Bmax and little change in Kd. No significant difference was found in alpha 2-AR binding following monocular deprivation. Similar extent of down-regulation in beta-AR binding was confirmed in all layers of visual cortex using autoradiography.     

Associative connections of the visual area of the neuronally-isolated cat cortex

The associative pathways of the visual zone (fields 17 and 18) of the neuronal-isolated cortex of the cat were studied by the methods of Nauta-Gygax and Fink-Heimer. The cortex was isolated by the method proposed by M. M. Khananashvili (1961) by means of transection of projectional systems of the fibres connecting the cortex with subcortical structures in the site of their maximum concentration-in the internal capsule. Fields 17 and 18 were shown to have short associative pathways running both within the limits of the fields proper and to fields 17, 7 and to Clara-Bishop region disposed in the depth of the suprasylvian fissure. The site of termination of the associative libres was all layers of the cortex in some degree. It is assumed that the cytoarchitectonical fields in the neuronal-isolated cortex during conditioning interacts by means of intracortical fibres shown in the present investigation.     

An intracellular study of the contrast-dependence of neuronal activity in cat visual cortex

Extracellular recordings indicate that mechanisms that control contrast gain of neuronal discharge are found in the retina, thalamus and cortex. In addition, the cortex is able to adapt its contrast response function to match the average local contrast. Here we examine the neuronal mechanism of contrast adaptation by direct intracellular recordings in vivo. Both simple (n = 3) and complex cells (n = 4) show contrast adaptation during intracellular recording. For simple cells, that the amplitude of fluctuations in membrane potential induced by a drifting grating stimulus follows a contrast response relation similar to lateral geniculate relay cells, and does not reflect the high gain and adaptive properties seen in the action potential discharge of the neurons. We found no evidence of significant shunting inhibition that could explain these results. In complex cells there was no change in the mean membrane potential for different contrast stimuli or different states of adaptation, despite marked changes in discharge rate. We use a simplified electronic model to discuss the central features of our results and to explain the disparity between the contrast response functions of the membrane potential and action potential discharge in simple cells.     

Intrinsic and environmental factors in the development of functional maps in cat visual cortex

In the mammalian visual cortex, key neuronal response properties such as orientation preference and ocular dominance (OD) are mapped in an orderly fashion across the cortical surface. It has been known for some time that manipulating early postnatal visual experience can change the appearance of the OD map. Similar evidence for developmental plasticity of the orientation map has been scarce. We employed optical imaging of intrinsic signals to examine the contribution of intrinsic and environmental factors to the development of cortical maps, using the paradigms of strabismus, reverse occlusion and rearing in a single-orientation environment ('stripe-rearing'). For several weeks after induction of strabismus, the pattern of OD domains remained stable in young kittens. The isotropic magnification of the OD map matched the postnatal growth of the visual cortical surface during the same period. In reverse-occluded and in stripe-reared kittens, orientation preference maps obtained through the left and the right eye were very similar, although the two eyes had never shared any visual experience. We suggest that the geometry of functional maps in the visual cortex is intrinsically determined, while the relative strength of representation of different response properties can be modified through visual experience.     

Efficient discrimination of temporal patterns by motion-sensitive neurons in primate visual cortex

Although motion-sensitive neurons in macaque middle temporal (MT) area are conventionally characterized using stimuli whose velocity remains constant for 1-3 s, many ecologically relevant stimuli change on a shorter time scale (30-300 ms). We compared neuronal responses to conventional (constant-velocity) and time-varying stimuli in alert primates. The responses to both stimulus ensembles were well described as rate-modulated Poisson processes but with very high precision (approximately 3 ms) modulation functions underlying the time-varying responses. Information-theoretic analysis revealed that the responses encoded only approximately 1 bit/s about constant-velocity stimuli but up to 29 bits/s about the time-varying stimuli. Analysis of local field potentials revealed that part of the residual response variability arose from "noise" sources extrinsic to the neuron. Our results demonstrate that extrastriate neurons in alert primates can encode the fine temporal structure of visual stimuli.     

The response of cat visual cortex to flicker stimuli of variable frequency

We examined the possibility that neurons or groups of neurons along the retino-cortical transmission chain have properties of tuned oscillators: To this end, we studied the resonance properties of the retino-thalamo-cortical system of anaesthetized cats by entraining responses with flicker stimuli of variable frequency (2-50 Hz). Responses were assessed from multi-unit activity (MUA) and local field potentials (LFPs) with up to four spatially segregated electrodes placed in areas 17 and 18. MUA and LFP responses were closely related, units discharging with high preference during LFP negativity. About 300 ms after flicker onset, responses stabilized and exhibited a highly regular oscillatory patterning that was surprisingly similar at different recording sites due to precise stimulus locking. Fourier transforms of these steady state oscillations showed maximal power at the inducing frequency and consistently revealed additional peaks at harmonic frequencies. The frequency-dependent amplitude changes of the fundamental and harmonic response components suggest that the retino-cortical system is entrainable into steady state oscillations over a broad frequency range and exhibits preferences for distinct frequencies in the theta- or slow alpha-range, and in the beta- and gamma-band. Concomitant activation of the mesencephalic reticular formation increased the ability of cortical cells to follow high frequency stimulation, and enhanced dramatically the amplitude of first- and second-order harmonics in the gamma-frequency range between 30 and 50 Hz. Cross-correlations computed between responses recorded simultaneously from different sites revealed pronounced synchronicity due to precise stimulus locking. These results suggest that the retino-cortical system contains broadly tuned, strongly damped oscillators which altogether exhibit at least three ranges of preferred frequencies, the relative expression of the preferences depending on the central state. These properties agree with the characteristics of oscillatory responses evoked by non-temporally modulated stimuli, and they indicate that neuronal responses along the retino-cortical transmission chain can become synchronized with precision in the millisecond range not only by intrinsic interactions, but also by temporally structured stimuli.     

Interrelationship between differently spaced neurons in the auditory and motor zones of the cerebral cortex in cats

Multineuronal activity was studied in unrestrained cats with bundles of seven electrodes (tips dia. 50 mcm) chronically implanted in the auditory and motor cortex. Spikes of the highest and lowest amplitude were isolated from each neurogram by an amplitude discriminator. Functional connections between neurones located under different electrodes at a distance of up 540 mcm were defined by statistical dependence of the isolated spike series. In the auditory cortex, the distance at which it was possible to detect connections between high amplitude neurones (H-H) did not exceed 450 mcm, while between low amplitude neurones (L-L) it was 270 mcm. In the motor cortex, dependent relations for similar pairs of neurones (H-H) and (L-L) were found at all the studied distances up to 540 mcm. For mixed neuronal pairs (H-L and L-H) functional connections at different distances were differently expressed at various distances.     

Patterns of inputs to the parietal cortex efferent neurons from the motor cortex and cerebellum in the cat

The focus of the presentation will review the distribution of nitric oxide (NO)-producing sites in the digestive system in mammals and nonmammalian vertebrates and will center on the roles that NO plays in modulating physiological and pathophysiological functions in digestive system.     

Effects of gaze on apparent visual responses of frontal cortex neurons

Previous reports have argued that single neurons in the ventral premotor cortex of rhesus monkeys (PMv, the ventrolateral part of Brodmann's area 6) typically show spatial response fields that are independent of gaze angle. We reinvestigated this issue for PMv and also explored the adjacent prearcuate cortex (PAv, areas 12 and 45). Two rhesus monkeys were operantly conditioned to press a switch and maintain fixation on a small visual stimulus (0.2 degree x 0.2 degree) while a second visual stimulus (1 degree x 1 degree or 2 degrees x 2 degrees) appeared at one of several possible locations on a video screen. When the second stimulus dimmed, after an unpredictable period of 0.4-1.2 s, the monkey had to quickly release the switch to receive liquid reinforcement. By presenting stimuli at fixed screen locations and varying the location of the fixation point, we could determine whether single neurons encode stimulus location in "absolute space" or any other coordinate system independent of gaze. For the vast majority of neurons in both PMv (90%) and PAv (94%), the apparent response to a stimulus at a given screen location varied significantly and dramatically with gaze angle. Thus, we found little evidence for gaze-independent activity in either PMv or PAv neurons. The present result in frontal cortex resembles that in posterior parietal cortex, where both retinal image location and eye position affect responsiveness to visual stimuli.     

NCAM 180 in the postnatal development of cat visual cortex: an immunohistochemical study

The neural cell adhesion molecule (NCAM) consists of three major isoforms with differing extents of intracellular domains. The largest, NCAM 180, may play an important role in the development and stabilization of cell contacts because of its interaction with the cytoskeleton, its accumulation at contact sites between cells, and age-dependent modifications of the immunoreactivity of its intracellular domain. The developmental expression pattern of NCAM 180 was examined in the cat visual cortex to explore its relation with the age-dependent decline of synaptic malleability. Western blot and immunohistochemical analyses were carried out by using a monoclonal antibody (D3) directed against an epitope of the intracellular domain specific to NCAM 180 and antibodies against all NCAM isoforms. The latter revealed a similar time course of increased expression during development by both Western blot and immunohistochemical analysis. In contrast, the D3 antibody showed an age-dependent increase of immunoreactivity by Western blot analysis and a decrease of reactivity by immunohistochemistry. In addition, the D3 antibody revealed characteristic developmental changes of immunoreactivity in the neuropil and distribution of immunopositive neuronal cell bodies in the different cortical laminae. The observations from this and another study (Kramer et al., 1997) suggest that the D3 antibody-specific NCAM 180 epitope is masked during the stabilization of connectivity.     

Distribution of inhibitory synapses on the somata of pyramidal neurons in cat motor cortex

The mechanisms by which cortical neurons perform spatial and temporal integration of synaptic inputs are dependent, in large part, on the numbers, types, and distributions of their synapses. To further our understanding of these integrative mechanisms, we examined the distribution of synapses on identified classes of cortical neurons. Pyramidal cells in the cat motor cortex projecting either to the ipsilateral somatosensory cortex or to the spinal cord were labeled by the retrograde transport of horseradish peroxidase. Entire soma of selected corticocortical and corticospinal cells were examined using serial-section electron microscopy. The profiles of these somata and the synapses formed with each of these profiles were reconstructed from each thin section with a computer-aided morphometry system. All somatic synapses were of the symmetrical, presumably inhibitory type. For both cell types, these synapses were not homogeneously distributed over the somatic membrane, but were clustered at several discrete zones. The number and density of synapses on the somata of different corticocortical and corticospinal neurons were not significantly different. However, the density of these synapses was inversely correlated with the size of their postsynaptic somata. We discuss the significance of these findings to the integrative properties of cortical neurons.     

Hebbian induction of LTP in visual cortex: perforated patch-clamp study in cultured neurons

1. To see whether presynaptic activation paired with postsynaptic depolarization is necessary for the induction of long-term potentiation (LTP) in visual cortex or whether an activation of postsynaptic receptors in conjunction with depolarization is sufficient, we carried out perforated patch-clamp recordings with nystatin from cultured cortical neurons of rats. 2. Recorded neurons were monosynaptically activated either by electrical stimulation of an adjacent neuron or by direct activation of glutamate on "hot spots" of dendrites through iontophoresis or pressure ejection. In experiments in which cultured neurons were stained immunocytochemically with antibody against synaptophysin after electrophysiological recordings, hot spots were found to correspond to probable synaptic sites. 3. Excitatory postsynaptic currents (EPSCs) evoked by test stimulation applied to the adjacent neuron at 0.1 Hz were recorded at a holding potential of -60 or -70 mV for 5-10 min after an establishment of the whole cell recording configuration. Then, stimulation was paired with postsynaptic depolarization (0 mV for 200 ms) at 1 Hz for 30 or 60 s. LTP of EPSCs was induced in 7 of the 15 cells from which stable recordings were obtained for 18-30 min after pairing. 4. When postsynaptic depolarization was paired with direct glutamate application in the absence of presynaptic stimulation in 12 cells, only 1 showed LTP. Postsynaptic depolarization alone did not induce LTP in any of the six cells tested. Also, presynaptic stimulation alone did not induce LTP in any of the five cells tested. 5. These results suggest that the concurrent activation of presynaptic elements with postsynaptic depolarization is necessary for the induction of LTP in visual cortex.     

Reaction of visual cortex neurons to cross-like figures during local inhibition blockade

Incidental finding of a primary malignant lymphoma of the ovary in a 20-year-old patient is presented. Two and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis.