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Distribution of parvalbumin immunoreactivity in the visual cortex of Old World monkeys and humans.

The macaque visual system has been frequently used as a model for understanding functional aspects of human vision. There are, however, few studies directly comparing biochemically defined neuronal populations in the visual cortex of the two species. In this study we compared the distribution and morphological features of the parvalbumin-immunoreactive neuronal subpopulation within humans and Old World monkeys (Macaca fascicularis and Macaca mulatta) by using monoclonal antibodies against the Ca2(+)-binding protein parvalbumin (PV), a neuronal marker in the vertebrate cerebral cortex. Characteristic laminar density and distribution of PV is observed, matching that seen with cytochrome C-oxidase and gamma-aminobutyric acid (GABA) immunoreactivity. Thus, parvalbumin is prominent in the layers receiving afferents from the dorsal lateral geniculate nucleus. Terminal fields are rich in layer IVA and IVC and moderate in the blob-region of layer II-III of the monkey cortex. In the human visual cortex only layer IVC displays rich terminal fields. Parvalbumin is present in neurons within all layers of the cortex except layer I. Parvalbumin-immunoreactive (PV-ir) axons occur in different lamellae of the white matter containing axons belonging to association or projection neurons. The estimation of PV-ir neurons, determined for 50 microns-wide columns through the thickness of area 17, shows that the percentage of the total neuron number in area 17 of humans containing PV is 6.8 +/- 2.0%, and in the macaque monkey, 11.5 +/- 2.9%. The perikaryal area of PV-ir neurons varies according to the layer and is comparable in humans (109.3 +/- 40.8 microns2) and monkeys (94.3 +/- 29.5 microns2). However, the relative number of large PV-ir neurons is higher in humans. The immunoreactive product fills the thinnest cell processes and the shape of PV-ir neurons can be easily traced with the aid of a camera lucida. The shape of the neurons is similar in the two species studied, and they probably belong to non-spiny stellate, double-bouquet, chandelier, and basket cell classes. This study shows that parvalbumin acts as a marker for a subpopulation of interneurons in area 17, but it is also present in the geniculocortical as well as in corticocortical pathways. Moreover, the Old World monkey and human visual cortices have a similar, but not identical, distribution of this important calcium-binding protein.

Animals

[Neuronal specialization of the motor cortex in normal rabbits and following destruction of the visual cortex].

The activity of neurones of the anterolateral part of the motor cortex in food-acquisition behaviour was compared in two control rabbits and in three rabbits after the operation of bilateral ablation of the striatal cortex. In two of three operated rabbits the pattern of behavioural specialization lost considerably the specificity peculiar to the motor cortex (predominance of G-neurones activated in grasping of food), approaching (but not becoming identical) the pattern of specialization of the visual cortex neurones: the number of G-neurones decreased in a half, and the number of L-neurones (activated in connection with the acts of instrumental food-acquisition behaviour which animals were trained to in the experimental cage) was doubled. Changes of the activity were significantly less expressed in the third operated rabbit. The number of the neurones activated in food-acquisition behaviour in operated rabbits in comparison with the control ones was reduced in the upper layers of the cortex and increased in the lower layers. The resemblance is discussed of the basic processes of animals learning and behaviour recovery.

Animals

Response properties of neurons in the visual cortex of the rat.

Response properties of neurons in the visual cortex, area 17, of Long Evans pigmented rats were investigated quantitatively with computer-controlled stimuli. Ninety percent of the cells recorded (296/327) were responsive to visual stimulation. The majority (95%, 281/296) responded to moving images and were classified as complex (44%), simple (27%), hypercomplex (13%) and non-oriented (16%) according to criteria previously established for cortical cells in the cat and monkey. The remaining 5% of the neurons responded only to stationary stimuli flashed on-off in their receptive field. Results of this study indicate that neurons of the rat visual cortex have properties similar to those of cells in the striate cortex of more 'visual' mammals.

Animals

Transcallosally evoked responses in the visual cortex of normal and monocularly enucleated rabbits.

In visual cortex of normal adult rabbits, callosal projections are restricted to a 2 mm wide band at the area 17/18 border. In adult rabbits which are monocularly enucleated (ME) on the day of birth, the callosal zone extends 4 mm into the medial region of area 17 in the cortex ipsilateral to the remaining eye. In this study, the function of these anomalous callosal projections in ME rabbits was investigated using electrophysiological techniques. A microelectrode was placed in the visual cortex ipsilateral to the enucleated eye at the 17/18 border, bipolar stimulating electrodes were placed in a homotopic location in the contralateral cortex, and averaged evoked responses (AERs) to stimulation were recorded. The stimulating electrodes were then moved mediolaterally in 1 mm steps, and the AERs were recorded for each location of the stimulating electrodes. In the normal rabbit, a maximal short latency evoked response was recorded when the stimulating electrodes were at a location homotopic to the recording electrode. When the stimulating electrodes were moved a distance of 1 mm or more from this optimal position, this short latency response was either absent or dramatically decreased in amplitude, reflecting the precise topographic pattern of the normal callosal projection. In contrast, in ME rabbits, a consistent response was evoked at the 17/18 border when the stimulating electrodes were moved as much as 3 mm medial to the homotopic position. Since antidromically activated responses and both pre- and postsynaptic orthodromically activated responses contribute to the AER, recordings were also made from single cells in some animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Transition from developing to mature patterns of acetylcholinesterase activity in rat visual cortex: implications for the time-course of geniculocortical development.

Patterns of acetylcholinesterase (AChE) histochemical staining in cortical area 17 differ in infant and mature rats. In infants, intense AChE activity is seen as a band corresponding to layer IV and deep layer III of the visual cortex, and this staining is associated with terminal fields of geniculocortical neurons. In adult animals, AChE activity is densest in deep layer IV and layer V and is associated with projections originating in the basal forebrain. The present study investigated the transition from developing to mature patterns of AChE staining in visual cortex. Unilateral lesions were placed in either the lateral geniculate body or the basal forebrain of rats postnatal days 8 (P8) to adulthood; the effects of these lesions on patterns of AChE activity in visual cortex were studied with histochemical techniques and optical densitometry. Lesions involving the lateral geniculate body markedly reduce AChE activity in visual cortex of P12 rats, had moderate effects in P20 rats, and had no apparent effect on AChE activity of visual cortex of rats aged P40 and older. Lesions of basal forebrain had little effect on AChE activity in visual cortex of P12 animals, increasing effect in P15-35 rats, and eliminated much of AChE staining in visual cortex of adults. The period of transition from developing to mature patterns of AChE activity in visual cortex of animals bilaterally enucleated at birth was not different from the period of transition in normally sighted animals. These data indicate that mature patterns of AChE activity in visual cortex are not achieved until well into the second month of life. If transient AChE expression is characteristic of geniculocortical neurons during the period of time in which axons are proliferating within visual cortex, then these data indicate that geniculocortical connections may be forming well into the second month of life in the rat.

Acetylcholinesterase

The distribution of M1 and M2 muscarinic acetylcholine receptor subtypes in the developing cat visual cortex.

The binding site characteristics and ontogenesis of [3H]pirenzepine ([3H]PZ) (M1 receptor) and [3H]oxotremorine-M ([3H]OXO-M) (M2 receptor) binding sites were investigated in the cat visual cortex. Scatchard analysis of [3H]PZ binding in adult cat visual cortex revealed a single site with a Kd of 17.3 nm and a Bmax of 352.45 fmol/mg protein. [3H]OXO-M also bound to a single site with a Kd of 7.1 nM and a Bmax of 256.39 fmol/mg protein. Receptor autoradiography revealed that [3H]PZ binding sites were present only in telencephalic structures while [3H]OXO-M sites were distributed heterogeneously throughout the brain. [3H]PZ binding sites in adult visual cortex were present in the superficial and deep cortical layers with the densest labeling in layer I and a distinct band in layer V. [3H]OXO-M sites also avoided the middle cortical layers, but were most prominent in layers V and VI with less pronounced binding in layers I and II. Deafferentation of extrinsic inputs to the visual cortex did not reduce [3H]PZ nor [3H]OZO-M binding, but neuron-specific excitotoxic lesions of visual cortex abolished both populations of binding sites. This indicates that both populations of binding sites are located on cells intrinsic to the cortex. In early postnatal life, both [3H]PZ and [3H]OXO-M binding sites were localized to intermediate cortical layers. Following this, the laminar distribution of both populations redistributed; each with its own idiosyncratic profile. By postnatal day 49, [3H]PZ binding sites redistributed into the superficial and deep layers, the pattern of adult animals, while [3H]OXO-M sites maintained a pattern similar to younger animals, with substantial binding persisting in layer IV. As late as postnatal day 70, well after [3H]PZ binding sites had achieved their mature laminar pattern, [3H]OXO-M binding sites in visual cortex had not achieved their characteristic adult pattern. In addition, the normal laminar redistribution of both [3H]PZ and [3H]OXO-M binding sites during postnatal development of the cat visual cortex was prevented by eliminating cortical afferents in early postnatal life. This indicates that muscarinic receptor rearrangement in development is dependent upon cortical input or output.

Animals

Direct projections from thalamic intralaminar nuclei to extra-striate visual cortex in the cat traced with horseradish peroxidase.

Thalamic projections to the visual cortex were investigated using the Horseradish peroxidase tracing technique. Besides confirmation of a distinct origin of thalamic projections to striate and extra-striate visual cortex, afferents of the intralaminar nuclei (ILN) to visual cortex were demonstrated. These projections of ILN were shown to be specific in that they terminate in areas 18, 19 and Clare Bishop but not area 17. The coupling of these intralaminar projections on to the extra-striate visual system is considered with respect ot orientation of gaze.

Animals

Genesis of GABA-immunoreactive neurons in the ferret visual cortex.

The pattern of neurogenesis of GABA-immunoreactive neurons in the ferret primary visual cortex was determined using immunohistochemical and 3H-thymidine autoradiographic techniques. Neurons in the visual cortex of the ferret undergo their final cell division during a period extending from embryonic day 20 (E20) to postnatal day 14 (P14) and follow an inside-out pattern of neuronal production (Jackson et al., 1984) similar to that observed in other mammals. Earlier-generated neurons are found at deeper cortical positions in the adult than are those generated later. Layer I is an exception to this rule, since neurons destined for this layer are produced at both the beginning and end of neurogenesis. In this study, the pattern of neurogenesis of GABA-immunoreactive neurons is compared to the pattern observed for nonimmunoreactive neurons. The overall pattern of cortical neurogenesis (inside-out pattern) is similar for GABA-immunoreactive neurons and neurons that are not GABA-immunoreactive. However, the GABA-immunoreactive neurons born on a given day of development are more broadly distributed across the radial axis of the adult cortex than are nonimmunoreactive neurons generated on the same day. GABA-immunoreactive neurons generated later in neurogenesis are, on average, slightly smaller than those generated early. If GABA-immunoreactive neurons in the visual cortex are interneurons, then these findings suggest that interneurons follow the same pattern of neurogenesis as do projecting neurons in the visual cortex.

Animals

Naso-temporal asymmetry of visual perception and of the visual cortex.

The decrease of visual performance from the fovea towards the periphery depends upon the task tested. The slope of the decrease is generally steeper for hyperacuity than for spatial resolution and is steeper in the nasal than in the temporal hemifield. The naso-temporal asymmetry in the periphery of the visual field, beyond 20 deg eccentricity, is much more pronounced for hyperacuity than for spatial resolution. The psychophysical results show a close correlation to the cortical organization as revealed by autoradiography.

Adult

[Interhemispheric relations of the cat visual cortex following unilateral polarization of the secondary visual area].

In 40 anesthetized cats, evoked potentials following light flashes during unilateral polarization of the secondary cortical visual area with DC anode (2-10 mcA) were studied in symmetrical centers of the 17th and 18th fields. Four phases of interhemisphere interrelationships between the 18th field's symmetrical centers were shown: 1 -- extracallosal phase of synergic depression; 2 -- callosal phase of dominant interrelationships; 3 -- callosal phase of synergic depression; 4 -- callosal-extracallosal phase of dominant interrelationships. In symmetrical centers of the 17th field, the only 1 extracallosal phase of synergic depression was observed during which the transcallosal modulation of nervous processes occurred. The data obtained are interpreted from the standpoint of the role of dominanta in interhemisphere interrelationships.

Animals

Noradrenergic control of ocular dominance plasticity in the visual cortex of dark-reared cats.

In the visual cortex of cats which had been dark-reared for several months since the time before natural eye opening, a cortical infusion of 6-hydroxydopamine (6-OHDA), a noradrenaline (NA)-related neurotoxin, partially suppressed a usual shift in ocular dominance following brief monocular lid suture, causing a significant loss of binocular cells. This partial shift in ocular dominance (U-shaped histogram) was also observed typically in the control hemisphere of cats which were subjected to dark-rearing for more than a year. Furthermore, the expected shift in ocular dominance following monocular deprivation was blocked by a direct cortical infusion of D,L-metoprolol, a selective beta 1-adrenergic receptor antagonist. The blockade was not obtained by D-metoprolol, a biologically inert stereo-isomer, under the comparable condition. In contrast, exogenous L-NA gave rise to an obvious shift in ocular dominance toward the non-deprived eye. The present results suggest that the NA-beta 1 adrenoreceptor system was necessary to maintain the ocular dominance plasticity in the visual cortex of dark-reared cats.

Animals

Plasticity in cat visual cortex restored by electrical stimulation of the locus coeruleus.

It has been proposed that the presence of noradrenaline (NA)-containing terminals and NA-related receptors within the visual cortex is necessary to maintain the high level of neuronal plasticity in the immature visual cortex of kittens. In the present study we wanted to show whether electrical stimulation of the locus coeruleus (LC), which contains the somata of these cortical NA fibers, can restore neuronal plasticity to the normally aplastic visual cortex of juvenile and adult cats. We consistently found a significant loss of binocular cells in the visual cortex of mature animals which had monocular vision for only 12 h dispersed over 6 days (2 h a day, otherwise kept in the dark) in combination with concurrent LC stimulation. This result was interpreted as indicating that endogenous NA released from NA terminals restored susceptibility to monocular vision in the mature visual cortex. We next examined how long the restored plasticity lasts in the same animals after the LC stimulation was ended. The animals revived from the first recording session were either returned to the same daily schedule of brief monocular exposure (light/dark = 2/22 h) as before, or subjected to the usual monocular lid suture and kept in a cat colony environment (light/dark = 16/8 h). The LC electrodes had been removed and no more electrical stimulation was delivered at this stage. In the animals subjected to reiteration of brief monocular exposure, the state of reduced binocularity gradually returned to normal over a period of 2-3 weeks after stopping LC stimulation. We calculated that the revived plasticity disappeared at an average rate of a 22% loss every 7 days. This result sharply contrasted with the result obtained in the animals subjected to usual monocular lid suture. In this test the state of reduced binocularity continued for at least the next 3 weeks, suggesting that the restored plasticity was sustained throughout a period of 3 weeks (longest term tested). The different results obtained in the two paradigms may be explained by the different strength of binocular imbalance in the two tests imposed on the visual cortex in which neuronal plasticity was restored partially.

Animals

Regional distribution of binding sites for neuropeptide Y in cat and monkey visual cortex determined by in vitro receptor autoradiography.

The goal of this study was to elucidate the precise regional and laminar distribution of neuropeptide Y (NPY) binding sites in feline and primate visual cortex. By means of in vitro receptor autoradiography, NPY binding sites in primate and feline visual cortex were specifically labeled with 3H-NPY. In cat area 17, the highest density of NPY-binding sites was present in lamina I and the upper half of lamina II. The density then gradually decreased towards lamina VI. Areas 18 and 19 exhibited a similar binding site-density profile. The decrease in density from superficial to deep layers was more gradual in area 18 than in areas 17 and 19. In monkey primary visual cortex (V1), layer IVc presented a high concentration of NPY binding sites, in addition to a dense zone of binding sites in layer I. Monkey secondary visual cortex (V2) displays a similar dense zone in layer I, but lacks such high density of NPY binding sites in layer IV. Therefore, the border between primary and secondary visual cortex coincides with the abrupt disappearance of this latter high density in layer IV. In cat as well as in monkey visual cortex, no significant differences were found between regions representing central vision and those representing the peripheral parts of the visual field. Comparison of our results for NPY binding sites with the distribution of alpha 1-adrenergic receptors, as recently described by Rakic et al. (J. Neurosci. 8(10):3670-3690, 1988) for primate and Parkinson et al. (Brain Res. 457:70-78, 1988) for feline visual cortex, revealed that those two patterns are very similar.

Animals

Effects of serial unilateral and serial bilateral visual cortex lesions on brightness discrimination relearning in rats.

In Experiment 1, rats with serial unilateral (SU), serial bilateral (SB), or one-stage bilateral (B) visual cortex lesions (areas 17, 18 and 18a) were compared in their retention of a preoperatively learned brightness discrimination. Both the first-stage and second-stage lesions for the SU and SB groups involved the same amount of cortical tissue and the same composite areas of visual field projection in primary and extraprimary visual cortex. Groups SU and SB showed substantial savings of the brightness discrimination after the completed bilateral visual cortex removals, while Group B showed a complete postoperative loss. In Experiment 2, the effects of two additional types of serial bilateral visual cortex lesions were investigated. These involved the medial and then lateral aspects of visual cortex in two stages (ML), or vice versa (LM). Once again, the serial bilateral lesion groups (SB, ML, and LM) showed substantial savings of the discrimination after the completed lesion, while Group B showed a complete post-operative loss. These results demonstrate a general advantage of serial damage over one-stage damage to visual cortex in recovery of a preoperatively learned brightness discrimination and indicate that the serial lesion effect is not specific to interhemispheric relationships.

Animals

Development of neuronal responses in cat posteromedial lateral suprasylvian visual cortex.

We studied the normal development of responses to visual stimulation among neurons in the posteromedial lateral suprasylvian (PMLS) visual cortex, an extrastriate visual cortical area in cats. Recordings were made from 495 single neurons in 19 kittens that were 2, 3, 4, 8, or 12 weeks of age, and the results were compared with those from normal adult cats. The percentage of neurons that respond to light increased from 57% in 2-week-old kittens to approximately adult values in 8-week-old kittens (81%). The strength and consistency of neuronal responses also increased with age. Nearly all of the responsive cells had well-defined excitatory receptive-field centers, and the receptive-field center sizes were similar to adults at all ages studied. However, few cells (5%) had inhibitory receptive-field surrounds in 2-week-old kittens. The incidence of surround inhibition increased to adult levels (about 40% of the cells) by 8 weeks of age, and the strength of surround inhibition also increased with age. Most cells responded best to moving stimuli in 2-week-old kittens, just as in adults. However, only about 20% of the responsive cells were direction sensitive at 2 weeks of age. The percentage of direction-sensitive cells increased gradually with age and reached approximately adult values by 8 weeks of age (74%). Once cells developed complete direction selectivity, with no response in the null direction, directional tuning width was similar to that in adults. When tested with slits of light flashed at various orientations or with spots and slits moving in various directions, few cells (8% or less) showed orientation selectivity at any age, just as in adults. Most of the cells were binocularly driven, and the ocular dominance distribution was similar to adults at all ages studied. These results indicate that many response properties of PMLS neurons are similar to those of adults as early as 2 weeks of age, soon after the time of eye opening. However, some properties show marked developmental changes. The mechanisms and sources of these changes are considered. In addition, the relevance of these results to mechanisms of compensation following early damage to visual cortical areas 17, 18 and 19 is discussed.

Aging

Intracortical microstimulation of neurons in the visual cortex of the cat.

The response of visual cortex neurons to local intracortical microstimulation was measured in the anesthetized cat. When the recording microelectrode was very close (about 20 micrometers) to the tip of the stimulating electrode, threshold currents as low as 10 micro A were capable of firing neurons. Over a 20-fold range in distance from the site of stimulation, an 80-fold increase in threshold current was observed. The mean latency of activation for 30 neurons tested with intracortical stimulation was 2.88 +/- 0.45 msec. The majority of these cells were probably synaptically activated. The mean threshold current for these neurons was 0.55 +/- 0.12 mA (N = 30). These values were significantly smaller than the thresholds found previously when stimulating electrodes were located on the pia-arachnoid surface of the visual cortex.

Animals

The pharmacology of synapses formed by identified corticocollicular neurons in primary cultures of rat visual cortex.

Primary cultures of neurons from the visual cortex of 7-10-d-old Long Evans rats were used to study the pharmacology of synaptic transmission. Dissociated cells were grown either in mass cultures, which contained 8000-10,000 neurons, or in miniature island cultures of 50-100 cells. Prior to dissociation, cells in layer V of visual cortex that project to the superior colliculus were labeled in vivo by retrograde transport of fluorescent latex microspheres-a permanent fluorescent marker. After 2 d to 8 weeks in culture, labeled neurons were identified by epifluorescent illumination, and electrophysiological recordings were obtained from a labeled cell and, simultaneously, from a nearby unlabeled neuron in the same field of view. The 2 neurons were stimulated sequentially by current injection and the pharmacology of evoked postsynaptic potentials (PSPs) was investigated. In mass cultures, relatively few pairs of neurons from which we recorded were synaptically connected, although nearly every cell exhibited abundant spontaneous EPSPs and IPSPs. Neurons grown on island cultures generally did not exhibit spontaneous synaptic activity; however, stimulation of one of the cells in a pair frequently elicited a short-latency PSP in the follower neuron. Retrogradely labeled corticocollicular neurons produced only excitatory PSPs in follower cells, while unlabeled neurons were either excitatory or inhibitory. Three antagonists of excitatory amino acid receptors, kynurenic acid, piperidine dicarboxylic acid, and gamma-D-glutamylglycine, completely blocked EPSPs produced by labeled corticocollicular neurons, as well as EPSPs produced by nearly all of the unlabeled excitatory cells. We have previously shown that these compounds block both N-methyl-D-aspartate (NMDA)-type and non-NMDA receptors on cultured cortical neurons (Huettner and Baughman, 1986). The specific NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) did not alter short-latency EPSPs recorded in 1 mM Mg2+, but did reduce longer-latency EPSPs polysynaptic activity. Since responses mediated by the NMDA receptor are known to be antagonized by Mg2+ (Mayer and Westbrook, 1985), we perfused cultures with Mg2+-free medium and found that the falling phase of some monosynaptic EPSPs was prolonged. Addition of APV to Mg2+-free medium reduced the duration of the falling phase of EPSPs such that they returned to the time course obtained in 1 mM Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Calretinin-immunoreactive neurons in the primary visual cortex of dolphin and human brains.

A new class of gamma-aminobutyric acid (GABA)ergic neurons immunoreactive to the calcium-binding protein calretinin (CR) was demonstrated in primary visual cortices of the bottlenose dolphin (Tursiops truncatus) and humans (Homo sapiens). Comparative analysis revealed several differences between dolphin and human visual cortex in the laminar distribution of CR-positive perikarya, although general typology of the immunoreactive CR-positive neurons was similar in both species. Thus, in both human and dolphin primary visual cortex almost all CR-positive neurons are non-pyramidal, either fusiform or bipolar cells, oriented with their long axis along the radial axis of the cortex. Large multipolar stellate cells were also observed in layers I and VI. The CR-positive neurons in the dolphin visual cortex are concentrated almost exclusively in layer I and, to a lesser extent, in layer II. In all other layers (IIIa, b, IIIc/V and VI) of the dolphin visual cortex CR-positive neurons were only rarely seen. In the human primary visual cortex CR-positive neurons are located mainly in layers II, III and IVa, b, c, with considerably lower densities of these cells observed in layers V and VI. CR-positive neurons in layer I of the human visual cortex are represented by Cajal-Retzius horizontal cells, whereas no such cells were seen in layer I of the dolphin neocortex. The numerical density of CR-positive neurons in the dolphin primary visual cortex is significantly lower than in the area of cortex in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged