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Receptive field structure in the visual cortex: does selective stimulation induce plasticity?

Sensory areas of adult cerebral cortex can reorganize in response to long-term alterations in patterns of afferent signals. This long-term plasticity is thought to play a crucial role in recovery from injury and in some forms of learning. However, the degree to which sensory representations in primary cortical areas depend on short-term (i.e., minute to minute) stimulus variations remains unclear. A traditional view is that each neuron in the mature cortex has a fixed receptive field structure. An alternative view, with fundamentally different implications for understanding cortical function, is that each cell's receptive field is highly malleable, changing according to the recent history of the sensory environment. Consistent with the latter view, it has been reported that selective stimulation of regions surrounding the receptive field induces a dramatic short-term increase in receptive field size for neurons in the visual cortex [Pettet, M. W. & Gilbert, C. D. (1992) Proc. Natl. Acad. Sci. USA 89, 8366-8370]. In contrast, we report here that there is no change in either the size or the internal structure of the receptive field following several minutes of surround stimulation. However, for some cells, overall responsiveness increases. These results suggest that dynamic alterations of receptive field structure do not underlie short-term plasticity in the mature primary visual cortex. However, some degree of short-term adaptability could be mediated by changes in responsiveness.

Animals↗

Patchy propagators, brain dynamics, and the generation of spatially structured gamma oscillations.

Propagator theory of brain dynamics is generalized to incorporate a new class of patchy propagators that enable treatment of approximately periodic structures such as are seen in the visual cortex. Complex response fields are also incorporated to allow for features such as orientation preference and wave-number selectivity. The results are applied to the corticothalamic system associated with the primary visual cortex. It is found that this system can generate gamma ( > or = 30 Hz) oscillations during stimulation, whose properties are consistent with experimental findings on gamma frequency and bandwidth, and existence of fine-scale spatial structure. It is found that a potential resonance is associated with each reciprocal lattice vector corresponding to periodic modulations of the propagators. It is found that the lowest resonances are the most likely to give rise to noticeable spectral peaks and increases of correlation amplitude, length, and time, and that these aspects are prominent only if the system is close to marginal stability, in accord with previous measurements and discussions of cortical stability. These features also enable gamma resonances to be stimulus-evoked, with substantial resonance sharpening for relatively small changes in mean neural firing rate. The results also imply dependence of gamma frequency on stimulus features.

Action Potentials↗

Brief visual stimulation allows mapping of ocular dominance in visual cortex using fMRI.

We have used high spatial resolution (0.55 mm x 0.55 mm) functional magnetic resonance imaging (fMRI) to show that when stimulus duration is brief (<6 sec), the hyperoxic hemodynamic response to neural activity can resolve the columnar architecture of ocular dominance within the primary visual cortex of humans. Our fMRI maps of ocular dominance columns are strikingly similar in appearance, size, and orientation to those reported in the literature using optical imaging of intrinsic signals (OIS) in animal cortex and histology of post-mortem human specimens. We also demonstrate that under brief visual stimulation conditions, our results are consistent over repeated experiments. This is not the case for long duration stimuli (> or = 10 sec). A simulated random data set exhibited the same response properties as maps obtained when using these prolonged visual stimuli. Our results suggest that brief visual stimulation is essential for fMRI to successfully resolve ocular dominance columns using the hyperoxic phase of the hemodynamic response to neural activity at our prescribed spatial resolution.

Brain Mapping↗

Postnatal development of glial fibrillary acidic protein, vimentin and S100 protein in monkey visual cortex: evidence for a transient reduction of GFAP immunoreactivity.

In the cerebral cortex of some species, the gradual appearance of glial fibrillary acidic protein (GFAP) is often interpreted as reflecting the parallel maturation of neuronal connectivity. We studied the postnatal maturation of astrocytes in the primary visual cortex of Callithrix jacchus using antibodies against GFAP, vimentin and S100 protein as immunohistochemical markers. In the cortical grey matter of this species, the overall GFAP-immunoreactivity (IR) as measured by image analysis is high at birth (130% of the adult value), decreases until about 3 months (80%) and increases again towards adult values (100%). Vimentin-IR was high at birth, and declined towards 3 months and later. In contrast, S100-IR augmented postnatally in neuropil, and showed a laminar shift of maximum IR from layer IV to supragranular layers during ontogenesis. The decrease of GFAP-IR is predominantly due to changes in density of GFAP-positive (+) astrocytes within cortical tissue (newborn: 18,600 GFAP+astrocytes/mm3; 1 month: 11,600/mm3; 3 months: 5,700/mm3; adult: 10,200/mm3), while the overall number of astrocytes remained relatively constant as shown by the number of S100-positive astrocytic cell bodies. At times of low GFAP-IR a reduced area density of intermediate filaments was found in astrocytes by electron microscopy. The period of reduced GFAP-expression coincides with the time of prominent synapse remodeling in the visual cortex of marmosets. These data suggest that GFAP-expression may depend on functional conditions rather than time-dependent maturation.

Aging↗

Local circuit neurons of macaque monkey striate cortex: III. Neurons of laminae 4B, 4A, and 3B.

We continue an investigation of the organization of local circuit neurons (largely inhibitory, GABAergic neurons, with smooth or sparsely spined dendrites) in the primary visual cortex of macaque monkey (Lund, '87: J. Comp. Neurol. 257:60-92; Lund et al., '88: J. Comp. Neurol. 276:1-29). This account covers local circuit neurons of layers 4B, 4A, and 3B; these three layers each receive different intrinsic second-order relays of principal thalamic inputs as well as receiving primary thalamic inputs in the case of two of the three laminae (4A and 3B). The study shows the existence of a number of different local circuit neurons making interlaminar projections between 4B, 4A, and 3B; each provides specific cross links between different combinations of the three laminae. It is known that the functional properties recorded physiologically from layers 4B, 4A, and 3B differ from one another and so these anatomical cross links may allow for correlation between different attributes of visual stimuli, e.g., color or motion, while still enabling separate processing of these different attributes to proceed in each of the three layers and be passed on to extrastriate areas. Whereas no spine-bearing neurons of layers 4B, 4A, or 3B provide "feedback" circuits to layer 4C (the source of their major intrinsic excitatory afferents), some of the local circuit neurons provide precisely structured axon feedback projections to divisions of 4C. The local circuit neurons also project to either lamina 5 or lamina 6, but not both and to superficial layers 3A, 2, and 1. Some local circuit neuron axon projections are of a dimension that would be confined to single functional clusters, e.g., cytochrome-rich "blobs," others reach out far enough to contact nearest neighbor "unlike" functional clusters, and yet others spread far enough to link repeating clusters of single function.

Aging↗

Computer-assisted morphometric analysis of intrinsic axon terminals in the supragranular layers of cat striate cortex.

Qualitative and quantitative analyses of terminal arborizations of biocytin-labeled axon terminals were carried out in the cat primary visual cortex (V1). Extracellular iontophoretic injections of 5% biocytin were made into V1 of five adult cats. The animals were perfused 24-48 h after the injections. Labeled-axon fragments were considered to comprise two presumptive groups, according to the qualitative features, thickness, bouton features and appearance of terminal arbors. Forty axon fragments (20 for each presumptive group) were digitized using a microscope with motorized stage and a z-encoder, attached to a microcomputer. The densities of boutons, branching points and axon segments per mm of axon as well as axon segment length were used for comparison of the two groups. The two qualitative groups were confirmed to contain two axon types (I and II), according to cluster analysis of characteristics of the 40 axons in our sample. Forward stepwise discriminant analysis retained two variables as predictors of group membership: axonal length and bouton density. Parametric and non-parametric tests were employed for statistical comparisons (significance at P < 0.01). Type II axon fragments showed the greatest densities of boutons, axonal segments and branching points and the smallest values of length of segments ( P < 0.01). Both the qualitative and quantitative differences found for both types of axons suggest that they belong to different functional classes of neurons, namely spiny (type I) and smooth neurons (type II). Computer-assisted morphometric analysis of individual axon fragments seems to be a suitable approach with which different axon types can be objectively distinguished from each other.

Animals↗

Non-oriented cells of the striate cortex activated during smooth pursuit eye movements and steady fixations in behaving monkeys.

Extracellular recordings were carried out in the primary visual cortex of behaving monkeys. Neurons were activated by moving a visual stimulus on their receptive fields during periods of steady fixation and by moving their receptive fields (smooth pursuit eye movements) on a motionless visual stimulus. Regarding non-oriented cells, they turned out to be activated by the visual stimulation both during steady fixations and smooth pursuit eye movements. Therefore, the non-oriented cells we studied seem not to receive an extraretinal signal related to the slow eye movements.

Animals↗

Acute effects of alcohol on evoked potentials in visual cortex and superior colliculus of the rat.

This study examined the effects of alcohol on visually evoked potentials recorded from the primary visual cortex (VC) and superior colliculus (SC) of chronically implanted rats. Animals were given intraperitoneal injections of saline, and of 0.15, 0.5, 1.0 and 1.5 g ethanol/kg body weight on separate days. Evoked potentials were recorded at 5, 20, 40, and 60 min following injection. There were differential effects of both alcohol and habituation on the early versus late VC components. The amplitudes of the late components decreased over time and were also depressed by both the 1.0 and 1.5g/kg doses of alcohol. Amplitudes of the early components increased over time and were unaffected by the 1.0g/kg alcohol dose. The 1.5g/kg dose depressed the early negative component but augmented the early positive component. In contrast to the amplitudes, the latencies of both early components were increased at both the l.0 and 1.5g/kg doses. However, the latency of the late positive component was increased at only the 1.5 g/kg dose, while the latency of the late negative component was unaffected by any alcohol dose. In the SC, the peak amplitude of the early positive complex was unaffected by either habituation or alcohol. However, both the amplitude and latency of a later negative component (latency of 52 msec) were affected by alcohol. The 1.0 and 1.5g/kg doses decreased peak amplitude, while the latency was increased at the highest dose. These effects of alcohol on the SC component were in directions opposite to those resulting from habituation.

Animals↗

Visual and somatosensory evoked potentials are mediated by excitatory amino acid receptors in the thalamus.

In pentobarbital-anaesthetized rats early somatosensory evoked potentials (SEPs) were recorded from the sensory cortex in response to electrical stimulation of the contralateral forepaw and visual evoked potentials (VEPs) from the primary visual cortex in response to single light flashes. Microapplication of the specific non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the ventro-basal thalamus (VB) resulted in a pronounced decrease in amplitude and an increase in latency of SEPs, whereas injection of DNQX into the dorsal lateral geniculate nucleus (DGL) induced a pronounced decrease in amplitude and an increase in latency of VEPs. These changes were: (1) dose-dependent (DNQX 0.01-1.0 nmol), (2) receptor-specific, and (3) site-specific. In contrast, the specific NMDA antagonist 2-amino-7-phosphonoheptanoate (AP7; 0.5-5 nmol) did not affect SEPs after microapplication into the BV and less potently reduced the amplitude and increased the latency of VEPs after microapplication into the DGL. The present findings are consistent with the assumption that an excitatory amino acid serves as transmitter at synapses in the rat thalamus mediating the nervous impulses responsible for the generation of SEPs and of VEPs. In addition the results suggest that this transmitter preferentially interacts with non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

Attention and probability effects in the human occipital cortex: an optical imaging study.

A new imaging technique (event-related optical signal, EROS) reveals the time course of neural activity in selected cortical areas of normal human subjects. This technique was used to study the event-related activity in striate and extrastriate occipital areas in an experiment in which spatial selective attention and stimulus probability were manipulated. The results show that attention effects are evident in the initial response in extrastriate cortex (latency < 100 ms), but not in striate cortex, confirming previous modeling effects. They also show that the initial response in striate cortex is modulated by stimulus probability, suggesting the occurrence of pre-attentive memory phenomena in primary visual cortex.

Adult↗

Vision after early-onset lesions of the occipital cortex: I. Neuropsychological and psychophysical studies.

We analyzed the visual functions of two patients (MS, FJ) with bilateral lesion of the primary visual cortex, which occurred at gestational age 33 wk in MS and at postnatal month 7 in FJ. In both patients basic visual functions--visual acuity, contrast sensitivity, color, form, motion perception-are similarly preserved or modestly impaired. Functions requiring higher visual processing, particularly figure-ground segregation based on textural cues, are severely impaired. In MS, studied longitudinally, the deficits attenuated between the ages of 4.5 and 8 y, suggesting that the developing visual system can display a considerable degree of adaptive plasticity several years after the occurrence of a lesion. In FJ (age 18:9 to 20:6 y), who is more impaired, the recovery, if any, was less.

Adolescent↗

[Brain functional MRI of the visual cortex with echo planar imaging].

Brain functional MR imaging (fMRI) is a non invasive imaging method for detecting neural activity. We performed functional MRI of the visual cortex with gradient-echo echo planar imaging (GE-EPI) and spin-echo EPI (SE-EPI) using 1.5T MRI system. Visual stimuli was performed with a checkerboard patterns. Magnitude and temporal phase of correlation between each pixel's time-course and sine functions at the frequency of the stimulus was calculated. In all subjects, the activation area in visual cortex obtained from SE-EPI was smaller than that from GE-EPI. Temporal phase delay images from both GE-EPI and SE-EPI showed signal spread from the primary visual cortex to peripheral supplementary areas. Temporal phase analysis is important to discriminate the source of the hemodynamic response to neural activation in fMRI.

Echo-Planar Imaging↗

Theories of visual cortex organization in primates: areas of the third level.

This brief review has a few main points. (1) Early proposals on how extrastriate cortex is subdivided were inconsistent with each other, and differences in interpretation were not resolved. (2) Brodmann's proposal of two ring-like areas, 18 and 19, surrounding primary visual cortex gained great acceptance despite the lack of agreement among different investigators considering the same evidence. (3) The concepts of areas 18 and 19, transposed to signify V2 and V3, have had great impact on recent and even current theories of extrastriate visual cortex organization in primates. (4) Nevertheless, Brodmann's areas 18 and 19, as defined in humans and Old World monkeys, correspond to none of the fields currently proposed for these primates. (5) All or most mammals appear to have a V2, and there is now widespread complete agreement over the extent and organization of this area in all studied primates. V2 is commonly referred to as area 18 because of its correspondence to area 18 as defined by Brodmann is some mammals. Yet, we should recognize that V2 is about half the size of Brodmann's area 18 in Old World monkeys and humans. (6) Current concepts of V3 differ greatly from the ring-like area 19 of Brodmann. We question the validity and usefulness of retaining the concept of V3 in primates. Our proposal for DM and other visual areas along the outer border of V2 seems more consistent, not only with the evidence from New World monkeys, but with evidence from Old World and prosimian primates, and even mammals most closely related to primates (see Kaas and Preuss, 1993). In all of these primates and close relatives of primates, the evidence indicates that more than one field forms the outer border of V2.

Animals↗

Relationships between dendritic fields and functional architecture in striate cortex of normal and visually deprived cats.

We examined relationships between the pattern of geniculocortical innervation and the dendritic fields of cells in layer 4 of in cat primary visual cortex. Experiments were performed on normal animals and on cats in which the geniculocortical projection was altered by monocular deprivation or by the induction of divergent squint during the critical period. Thalamic afferents providing the input from the contralateral eye were anterogradely labeled by injecting the fluorescent tracer Dil into lamina A of the lateral geniculate nucleus. Intracellular staining with Lucifer yellow in slice preparations allowed simultaneous visualization of the morphology of individual cells and the thalamic afferents. Our results demonstrate that spiny stellate cells close to the upper and lower margin of the geniculocortical input have highly asymmetric dendritic fields, and thereby confine their dendrites to the termination zone of these afferents. This effect was specific for the cell class; it was not observed in pyramidal neurons. These dendritic asymmetries perpendicular to the laminar borders of spiny stellate cells were not altered by monocular deprivation or strabismus. In contrast, visual deprivation strongly influenced the dendritic arbors of spiny stellate cells near the borders between adjacent ocular dominance columns. In normal animals, the dendrites of cells near columnar borders remained preferentially within one column. These dendritic asymmetries became much more pronounced in strabismic animals. Monocular deprivation weakened the influence of the columnar borders on dendritic fields. Spiny stellate cells within the columns of the open eye exhibited a slight tendency to confine their dendrites to these columns. Cells in the columns of the deprived eye showed the opposite effect; they extended their dendrites preferentially into the adjacent columns of the open eye. These results demonstrate that the segregation of geniculocortical afferents into ocular dominance columns and its perturbation by manipulation of the visual input plays an important role in defining the morphology of cortical target cells. Thus, activity-dependent structural changes not only occur at the level of the presynaptic terminals, but also at the level of the postsynaptic target cells, and thereby contribute to build up the functional architecture of the cortex.

Animals↗

Axons and synaptic boutons are highly dynamic in adult visual cortex.

While recent studies of synaptic stability in adult cerebral cortex have focused on dendrites, how much axons change is unknown. We have used advances in axon labeling by viruses and in vivo two-photon microscopy to investigate axon branching and bouton dynamics in primary visual cortex (V1) of adult Macaque monkeys. A nonreplicative adeno-associated virus bearing the gene for enhanced green fluorescent protein (AAV.EGFP) provided persistent labeling of axons, and a custom-designed two-photon microscope enabled repeated imaging of the intact brain over several weeks. We found that large-scale branching patterns were stable but that a subset of small branches associated with terminaux boutons, as well as a subset of en passant boutons, appeared and disappeared every week. Bouton losses and gains were both approximately 7% of the total population per week, with no net change in the overall density. These results suggest ongoing processes of synaptogenesis and elimination in adult V1.

Animals↗

Fos expression in rat visual cortex induced by ocular input of ultraviolet light.

We used immunostaining for the cellular transcription factor Fos to assess patterns of neuronal activation in rat visual cortex during exposure to ultraviolet light. Exposure to monochromatic ultraviolet light (lambda max 360 nm: half-bandwidth 8.8 nm, 10 microW/cm2 at eye level) induced strong expression of Fos immunoreactivity in the primary visual cortex and associated cortical visual areas of dark-adapted rats. The stimulatory effect of ultraviolet light on Fos expression was related to exposure duration, was independent of stimulus novelty or phase of the circadian cycle in which exposure occurred, and it was mediated by a mechanism located in the eye. These results demonstrate that ocular input of ultraviolet light is capable of altering neuronal activity in cortical structures involved in visual processing and are consistent with the hypothesis that rodents may use ultraviolet light for vision.

Animals↗

Dark-rearing decreases NR2A N-methyl-D-aspartate receptor subunit in all visual cortical layers.

Maturation of the visual cortex is a visual experience-dependent process. It has been shown that visual input triggers changes in N-methyl-D-aspartate receptor (NMDAR) subunit expression in the visual cortex. However, no data are available on the layer distribution of these molecular changes. Here we describe the laminar distribution of the cells expressing the NMDAR subunits NR2A and NR2B in the rat primary visual cortex at postnatal day (P) 21 and 37 using anti-NR2A and anti-NR2B antibodies and a stereological method to count labelled neurons. The percentage of neurons expressing the NR2A subunit in the layers II-VI remained unchanged between P21 and P37 with a slight decrease in layer V. Dark-rearing from P21 to P37 induced a pronounced decrease of the staining intensity and a significant decrease in the percentage of NR2A-expressing neurons. The changes in NR2A expression caused by dark rearing occur at similar levels in layers II-VI. The percentage of NR2B-positive cells in the different cortical layers remains unchanged from P21 to P37. The NR2B pattern was not significantly affected by dark-rearing. Thusly, the expression of NR2A depends upon visual experience after P21.

Aging↗

Antibodies directed against tyrosine hydroxylase differentially recognize noradrenergic axons in monkey neocortex.

In previous immunohistochemical studies of monkey neocortex, we found that antisera directed against tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) appeared to label distinct populations of neocortical axons, which presumably were dopaminergic and noradrenergic, respectively. In the present study, we further evaluated the apparent selectivity of this rabbit anti-TH antiserum for cortical dopaminergic fibers in monkeys by comparing it with two other anti-TH antibodies, a mouse monoclonal and a sheep polyclonal. In addition, the latter two anti-TH antibodies were used in double-labeling studies with a rabbit anti-DBH antiserum. In both single- and dual-label studies, each anti-TH antibody visualized a similar population of cortical axons, although the number of labeled fibers differed across antibodies. That is, in some cortical regions and layers, both the sheep and mouse anti-TH antibodies labeled more cortical fibers than did the rabbit anti-TH antiserum. Thus, the former two antibodies appeared to identify a subpopulation of TH-containing fibers that the latter antibody did not. Dual-label experiments, involving the rabbit anti-DBH antiserum and either the sheep or mouse anti-TH antibodies, demonstrated numerous neocortical DBH-immunoreactive axons in which TH was not detectable immunohistochemically. The percentage of DBH-immunoreactive fibers that were single-labeled differed across cortical regions and with the anti-TH antibody employed. For example, in primary motor cortex the mouse anti-TH antibody did not label 99.4% of the DBH-positive fibers, whereas in primary visual cortex, 76.4% of the DBH-immunoreactive axons were identified by the sheep anti-TH antibody. The results of these studies indicate that many DBH-immunoreactive, presumably noradrenergic, axons in monkey neocortex are not visualized by anti-TH antibodies, and that the ability of anti-TH antibodies to identify noradrenergic cortical axons in monkeys differs substantially among anti-TH antibodies and across cortical regions. These findings may be consistent with previous reports suggesting that the TH molecule is present in different concentrations or molecular forms in dopaminergic and noradrenergic cortical fibers. Finally, this study demonstrates that the labeling characteristics of a particular anti-TH antibody must be carefully evaluated, particularly in studies of primate neocortex, in order to properly interpret the results of those studies.

Adrenergic Fibers↗