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Plasticity of excitatory synaptic transmission in kitten visual cortex depends on voltage-dependent Ca2+ channels but not on NMDA receptors.

Long-term potentiation (LTP) of excitatory synaptic transmission occurs in in vitro slices of cat and rat visual cortex. Earlier studies suggested that activation of N-methyl-D-aspartate (NMDA)-selective glutamate receptors is essential for the induction of LTP. However, our studies on kitten visual cortex demonstrate that LTP induction requires the activation of low-threshold Ca2+ channels in postsynaptic cells but not of NMDA receptors.

Animals↗

Plasticity of orientation preference maps in the visual cortex of adult cats.

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

Age Factors↗

Limits on activation-induced temperature and metabolic changes in the human primary visual cortex.

Changes in cerebral blood flow (CBF) and metabolism are now widely used to map and quantify neural activity, although the underlying mechanism for these changes is still incompletely understood. Magnetic resonance spectroscopy (MRS) at 3T, synchronized with a 32-s block design visual stimulation paradigm, was employed to investigate activation-induced changes in temperature and metabolism in the human primary visual cortex. A marginally significant increase in the local temperature of the visual cortex was found (0.1 degrees C, P = 0.09), excluding the possibility of a temperature decrease (95% confidence interval (CI) = 0.0-0.2 degrees C), which was previously suggested. A comparison with models of thermal equilibrium in the presence of blood flow suggests that an increase in heat production during activation, greater than or at least equal to that produced by the complete oxidative metabolism of the elevated glucose (Glc) utilization accompanying activation, would be required to offset the cooling effects of the increased blood flow. The total pools of glutamate (Glu), glutamine (Gln), myo-Inositol (mI), N-acetylaspartate (NAA), choline (Cho), and lactate (Lac) were not significantly affected by activation. Limits on Lac concentration changes were too weak to constrain theories of the metabolic use of elevated Glc consumption during stimulation, and emphasize the challenges of measuring even large Lac changes accompanying stimulation.

Adult↗

Neural responses in the primary visual cortex of the monkey during perceptual filling-in at the blind spot.

The phenomenon of perceptual filling-in demonstrates that physical stimuli presented on the retina do not necessarily correspond to surface perception, and that our visual system has mechanisms with which to interpolate missing information in order to construct continuous surfaces. Among its various forms, filling-in at the blind spot is one of the most remarkable. To study the neural mechanisms involved in filling-in at the blind spot, we recently conducted a recording experiment aimed at determining whether the neurons in the primary visual cortex (V1) that represent the visual field corresponding to the blind spot are activated when filling-in occurs. We found that neurons located in deep layers of the V1, particularly layer 6, respond to large stimuli that cover the blind spot and induce perceptual filling-in. These neurons tended to have very large receptive fields, which extended out of the blind spot, and preferred relatively large stimuli. We believe that neurons in the V1 region representing the blind spot encode information essential for perceptual filling-in at the blind spot.

Animals↗

Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

INTRODUCTION: Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia. MATERIALS AND METHODS: Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye. RESULTS: Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than subcortical mechanism. CONCLUSION: Suppression of metabolic activity in ODCs of V1 differs depending upon whether infantile strabismus is alternating or occurs in conjunction with unilateral amblyopia. Our findings reinforce the principle that unrepaired strabismus promotes abnormal competition in V1, observable as interocular suppression of ODCs.

Amblyopia↗

Ontogenetic changes in the level and subcellular distribution of protein kinase C in cat visual cortex.

Ontogenetic changes of the total activity and the subcellular distribution of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) were investigated in the cat visual cortex. Following homogenization of the tissue in Ca2+-free buffer and separation of membrane-bound and soluble protein kinase C, the enzyme was partially purified by diethylaminoethyl-cellulose chromatography. Total, membrane-bound and soluble enzyme activity were determined by measuring the phosphate incorporation into lysine-rich histone, a substrate for protein kinase C. It was found that the total activity level, while being low in the first 4 weeks, increased rapidly to peak values at 5 weeks of age and declined slightly thereafter. Although at all developmental stages most of the enzyme was recovered in the soluble fraction, the membrane-bound activity exhibited a considerable increase at 5 weeks of age, reflecting a relative shift of protein kinase C from the cytosol to the membranes. The increase and redistribution of protein kinase C activity coincide in time with the developmental phase during which the visual cortex is particularly susceptible to undergo use-dependent modifications. This finding is compatible with the hypothesis that protein kinase C-mediated phosphorylation processes are involved in activity-dependent modifications of neuronal transmission.

Aging↗

Characterization, distribution, and ontogenesis of adenosine binding sites in cat visual cortex.

In vitro autoradiographic techniques were used to characterize binding sites for 3H-cyclohexyladenosine (CHA) and 3H-5'-N-ethylcarboxamidoadenosine (NECA) in cat and kitten visual cortex. 3H-CHA binding sites in adult cat have a Bmax of 1,363 fmol/mg protein and a Kd of 6.8 nM. Displacement experiments indicate that 3H-CHA binds to an adenosine receptor similar to the A1-adenosine receptor described by other investigators. 3H-NECA binding sites in adult cat have a Bmax of 518 fmol/mg protein and a Kd of 15.4 nM. Displacement experiments do not allow us to identify this binding site unambiguously. Bmax values increase during postnatal development for both binding sites, peaking in adulthood for 3H-CHA and at 30 d for 3H-NECA. Kd values show neither consistent nor significant differences during postnatal development for either binding site. 3H-CHA and 3H-NECA binding sites are concentrated in layers 1-3 and upper layer 5 in the visual cortex of adult cats. These laminar patterns, however, change during postnatal development, showing the densest binding in the deep cortical layers (5 and 6) in kittens younger than 30 d of age and a fairly homogeneous binding in older kittens before achieving the adult distribution.

Animals↗

Functional mapping of horizontal connections in developing ferret visual cortex: experiments and modeling.

In cat striate cortex, patchy horizontal axonal projections link columns of similar orientation specificity. To assess the physiological correlates of such clustered projections, a new multisite stimulation technique was used to functionally map the pattern of horizontal synaptic inputs onto single layer 2/3 cells within tangential slices of developing ferret visual cortex. Twenty-four separate sets of horizontal fibers were stimulated within a 1200 microns strip of cortex, while evoked synaptic responses were recorded using whole-cell patch methods. For most cells, input maps demonstrated the presence of clustered horizontal connections in which multiple strong and weak synaptic responses were alternately evoked across the stimulated cortical region. Recordings from up to nine cells in a single slice revealed that patterns of synaptic input were closely correlated for cells in close proximity, and that this correlation decreased with distance, with no correlation at distances greater than 500 microns. To determine whether these physiological results were consistent with the known anatomical linkage of iso-orientation columns by clustered horizontal connections, mathematical analysis and computer simulations were performed upon orientation tuning maps obtained from optical imaging of activity-dependent intrinsic signals in mature ferret visual cortex. Optical imaging revealed an organization of iso-orientation domains consisting of broad regions of cortex across which orientation preference smoothly varied, together with "orientation centers" around which orientation preference was arranged in a pinwheel manner. The distribution of synaptic connections between different cortical sites was simulated by a model of functionally linked iso- orientation columns. Simulated synaptic input maps, generated by the same stimulation and recording arrangements used in our experimental protocol, accurately reproduced the observed patterns of clustered inputs onto experimentally recorded cells. These results indicate that even at the time of eye opening, prior to extensive visual experience, most cells receive patterns of synaptic inputs consistent with a clustered organization of horizontal connections that functionally link iso-orientation columns.

Animals↗

The activity of lysosomal enzymes in visual cortex of rabbits during experimental diabetes.

The activity of all principal groups of lysosomal enzymes (acid phosphatase, lipase, beta-galactosidase, sulphatase and cathepsin B) was measured in the visual cortex of rabbits with experimental diabetes. In the first stage of diabetes (21 days), it was observed that enzyme activities in the free fraction and in the membrane-bound fraction are decreased as compared to the initial values determined in healthy animals. In the later stages of diabetes (90-180 days), all lysosomal enzyme activities increased except for sulphatase. This indicated a superiority of catabolic processes in visual cortex cells in the course of experimental diabetes.

Animals↗

Differential expression of immediate-early genes, c-fos and zif268, in the visual cortex of young rats: effects of a noradrenergic neurotoxin on their expression.

We investigated the expression pattern of two immediate-early genes, zif268 and c-fos, under various visual conditions using immunohistochemical and northern blot analysis in the visual cortex of young rats. The basal expression of c-fos was low and was further reduced by dark rearing that lasted for one week. A marked and transient increase was induced upon visual stimulation applied immediately after dark rearing. Zif268 showed a relatively high basal level. Its expression was reduced by dark rearing of the animals, but returned rapidly to the basal expression level following the introduction of light. Administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a selective noradrenergic neurotoxin, suppressed the basal expression of c-fos messenger RNA. The response of c-fos to photo-stimulation was also significantly lower in the visual cortex of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-treated young rats. In contrast, no significant change in zif268 expression was detected between normal and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-treated animals. These findings suggest that differential expression of these immediate-early genes is involved in the activity-dependent regulation of cortical function. One possibility is that the noradrenergic system controls cortical function, including plasticity, by modifying the expression of c-fos.

Age Factors↗

The morphology and distribution of peptide-containing neurons in the adult and developing visual cortex of the rat. IV. Avian pancreatic polypeptide.

Immunocytochemical techniques were used to investigate the morphology and distribution of avian pancreatic polypeptide-like immunoreactive neurons in the visual cortex of albino rats at various ages from the first postnatal day to adulthood. In the adult, immunoreactive neurons were located in layers II to VI but were somewhat concentrated in the deeper cortical layers. The overwhelming majority of labelled cells exhibited morphologies characteristic of multipolar, bitufted and bipolar varieties of non-pyramidal neurons as described in Golgi preparations of rat visual cortex. However, a few immunoreactive pyramidal neurons were also observed. On the first postnatal day, a small number of immature non-pyramidal neurons were observed in the subplate region. Labelled cells appeared in the more superficial layers at the beginning of the second postnatal week and attained a distribution similar to that observed in adult animals during the third week. The morphological maturation of immunoreactive neurons occurred gradually during the first two postnatal weeks and at day 21, they appeared qualitatively indistinguishable from their adult counterparts.

Animals↗

Rapid eye-movement sleep deprivation does not 'rescue' developmentally regulated long-term potentiation in visual cortex of mature rats.

The age at which it is possible to obtain a usually age-limited (developmental) form of long-term potentiation (LTP) in rat visual cortex slices can be extended by suppressing rapid eye movement (REM) sleep. In this study, we examined whether REM sleep deprivation can also 'rescue' this type of LTP in older rats. Rats, 42-59 days of age, were either REM sleep-deprived for 7-10 days (n=8), or not deprived of REM sleep (control group, n=8). Brain slices from visual cortex were tested for the developmental form- and a related, non-developmental form of LTP. Three of the eight REM sleep-deprived animals and four of the eight non-deprived animals met criteria for a valid attempt to induce the developmental form of LTP. Though the non-age-regulated form of LTP could be obtained in all seven of these animals, the developmental form could not be elicited in any, indicating that REM sleep deprivation does not uniformly affect all forms of LTP in adult rats. We conclude that extended periods of REM sleep deprivation do not facilitate induction of developmentally regulated LTP once the animal is beyond a certain age.

Age Factors↗

Orientation selectivity of thalamic input to simple cells of cat visual cortex.

More than 30 years after Hubel and Wiesel first described orientation selectivity in the mammalian visual cortex, the mechanism that gives rise to this property is still controversial. Hubel and Wiesel proposed a simple model for the origin of orientation tuning, in which the circularly symmetrical receptive fields of neurons in the lateral geniculate nucleus that excite a cortical simple cell are arranged in rows. Since this model was proposed, several experiments and neuronal simulations have suggested that the connectivity between the lateral geniculate nucleus and the cortex is not well organized in an orientation-specific fashion, and that orientation tuning arises instead from extensive interactions within the cortex. To test these models we have recorded visually evoked synaptic potentials in simple cells while cooling the cortex, which largely inactivates the cortical network, but leaves geniculate synaptic input functional. We report that the orientation tuning of these potentials is almost unaffected by cooling the cortex, in agreement with Hubel and Wiesel's original proposal.

Animals↗

Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice.

The cAMP-dependent protein kinase (PKA) signalling pathway has been shown to play an important role in long-term potentiation (LTP) and depression (LTD), and ocular dominance plasticity in the visual cortex. In order to investigate further the involvement of individual PKA subunits in visual cortical plasticity, LTP and LTD in vitro and ocular dominance plasticity in vivo in the developing visual cortex were examined in mice lacking the RII alpha subunit of PKA. Here we show that LTP in layers II/III was decreased in RII alpha knockout mice, but LTD was almost unaffected, and the ocular dominance shift induced by monocular deprivation was also partially blocked. These data provide evidence that RII alpha is involved in LTP and ocular dominance plasticity, and further suggest that different afferent inputs could selectively activate particular subunits of PKA and thereby direct specific aspects of visual cortical plasticity.

Action Potentials↗

GAP-43 in adult visual cortex.

GAP-43 was purified from cat brain by a rapid isolation procedure and was used to raise highly specific polyclonal antibodies in rabbits. Immunoblots of proteins from adult cat, monkey and human visual cortex as well as bovine cortex also showed specific staining of a single protein that was present in both soluble and membrane fractions. Immunocytochemistry of both cat and human adult visual cortex showed that GAP-43 has a laminar distribution.

Adult↗

Areal, modular, and connectional organization of visual cortex in a prosimian primate, the slow loris (Nycticebus coucang).

Slow lorises (Nycticebus coucang) are nocturnal prosimian (i.e. strepsirhine) primates, closely related to bushbabies (Galago spp.). We examined the organization of visual cortex in four hemispheres from two slow lorises, using connectional and architectonic techniques. All hemispheres were flattened and sections stained for myelin and cytochrome oxidase (CO). Our results indicate, first, that the primary visual area (V1) in slow lorises has a system of small CO-dense blobs, as has been described in most other anthropoid and prosimian primates examined to date. The second visual area (V2) is characterized by broad, stripe-like zones of dense CO staining separated by zones of lighter staining. Loris V2 stripes are less distinct than those of anthropoid primates, and separate classes of thin and thick dark stripes are not apparent. However, V2 stripes are much better developed than in Galago, where they are virtually absent. Injections of wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in area V1 revealed reciprocal connections with area V2, and the middle temporal (MT) and dorsolateral (DL) extrastriate areas. Area MT was also identified by its distinctive, dense myelination. As has been reported in anthropoids, DL can be divided into separate caudal and rostral divisions, which differ in myelin and CO staining, and in the strength of their connections with V1. Taken together, our results suggest that many of the features that characterize visual cortex organization in anthropoid primates are present in prosimians and thus probably evolved early in primate history, prior to the diversification of modern primate groups.

Animals↗

Protein and RNA synthesis-dependent and -independent LTPs in developing rat visual cortex.

Multiple forms of synaptic potentiation have been described, but their involvement in development versus learning is unknown. To address this, we examined whether long-term potentiation (LTP) in visual cortex requires protein or RNA synthesis using slice preparations. Theta-burst stimulation of white matter induced two distinct types of LTP in layer 4. A slowly developing LTP, preferentially induced in juveniles, was blocked by protein and RNA synthesis inhibitors and was L-type calcium channel dependent. A quickly developing LTP, induced in juveniles and adults, was independent of macromolecular synthesis and required N-methyl-D-aspartate receptor activation. Thus, slow LTP might account for developmental plasticity in visual cortex including the activity-dependent refinement of neural circuitry while fast LTP might underlie the changes in synaptic strength that may participate in visual learning and memory.

2-Amino-5-phosphonovalerate↗