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PubMed1991

High-resolution optical imaging of functional brain architecture in the awake monkey.

Optical imaging of the functional architecture of cortex, based on intrinsic signals, is a useful tool for the study of the development, organization, and function of the living mammalian brain. This relatively noninvasive technique is based on small activity-dependent changes of the optical properties of cortex. Thus far, functional imaging has been performed only on anesthetized animals. Here we establish that this technique is also suitable for exploring the brain of awake behaving primates. We designed a chronic sealed chamber and mounted it on the skull of a cynomolgus monkey (Macaca fascicularis) over the primary visual cortex to permit imaging through a transparent glass window. Restriction of head position alone was sufficient to eliminate movement noise in awake monkey imaging experiments. High-resolution imaging of the ocular dominance columns and the cytochrome oxidase blobs was achieved simply by taking pictures of the exposed cortex when the awake monkey was viewing video movies alternatively with each eye. Furthermore, the functional maps could be obtained without synchronization of the data acquisition to the animal's respiration and the electrocardiogram. The wavelength dependency and time course of the intrinsic signal were similar in anesthetized and awake monkeys, indicating that the signal sources were the same. We therefore conclude that optical imaging is well suited for exploring functional organization related to higher cognitive brain functions of the primate as well as providing a diagnostic tool for delineating functional cortical borders and assessing proper functions of human patients during neurosurgery.

Animals↗
PubMed2002

Visual-vestibular and visuovisual cortical interaction: new insights from fMRI and pet.

PET and fMRI studies have revealed that excitation of the vestibular system by caloric or galvanic stimulation not only activates the parietoinsular vestibular cortex but also bilaterally deactivates the occipital visual cortex. Likewise, visual motion stimulation not only activates the visual cortex but also deactivates the parietoinsular vestibular cortex. These findings are functionally consistent with the hypothesis of an inhibitory reciprocal visual-vestibular interaction for spatial orientation and motion perception. Transcallosal visuovisual interaction between the two hemispheres was found by using half-field visual motion stimulation: activation of motion-sensitive areas hMT/V5 and deactivations of the primary visual cortex contralateral to the stimulated hemisphere. The functional significance of these inter- and intra-sensory interactions could be that they (A) allow a shift of the sensorial weight between two incongruent sensory inputs and (B) ensure a correspondence of the two hemispheres during evaluation of contradictory motion stimulation of the right and left hemifields. In terms of mathematical modeling, these findings may reflect the concepts of a sensory conflict mechanism or a mismatch between expected and actual sensory input.

Animals↗
PubMed2000

Multiple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex.

Short-term synaptic plasticity, in particular short-term depression and facilitation, strongly influences neuronal activity in cerebral cortical circuits. We investigated short-term plasticity at excitatory synapses onto layer V pyramidal cells in the rat medial prefrontal cortex, a region whose synaptic dynamic properties have not been systematically examined. Using intracellular and extracellular recordings of synaptic responses evoked by stimulation in layers II/III in vitro, we found that short-term depression and short-term facilitation are similar to those described previously in other regions of the cortex. In addition, synapses in the prefrontal cortex prominently express augmentation, a longer lasting form of short-term synaptic enhancement. This consists of a 40-60% enhancement of synaptic transmission which lasts seconds to minutes and which can be induced by stimulus trains of moderate duration and frequency. Synapses onto layer III neurons in the primary visual cortex express substantially less augmentation, indicating that this is a synapse-specific property. Intracellular recordings from connected pairs of layer V pyramidal cells in the prefrontal cortex suggest that augmentation is a property of individual synapses that does not require activation of multiple synaptic inputs or neuromodulatory fibers. We propose that synaptic augmentation could function to enhance the ability of a neuronal circuit to sustain persistent activity after a transient stimulus. This idea is explored using a computer simulation of a simplified recurrent cortical network.

2-Amino-5-phosphonovalerate↗
PubMed1994

Cortical area in the rat that mediates visual pattern discrimination.

In Experiment I, bilateral ablations of the caudolateral cortex involving Krieg's area 36 impaired discrimination of visual patterns but not delayed alternation. In Experiment II, the same type of lesions retarded postoperative learning to discriminate embedded visual patterns. In rats from the Experiment II tracers of axonal transport gave no signs of damage of the connections of the primary visual cortex. In agreement with this, Nissl stain of the dorsal lateral geniculate nuclei showed no neuronal loss or gliosis. These results suggest that caudo-lateral cortex in rats corresponds to the inferotemporal cortex of primates.

Animals↗
PubMed1978

The effects of dark rearing on the development of the visual cortex of the rat.

The effects of dark rearing on the development of the visual cortex has been studied in Wistar rats, as have the effects of subsequent light exposure on recovery. Five groups of animals were used: (1) light exposed until 30-40 days post partum (dpp) (2) dark reared until 30-40 ddp (3) dark reared until 80-120 dpp (4) dark reared to 21 dpp, then light exposed until 40 dpp (5) light exposed to 21 dpp and then dark reared until 40 dpp. Golgi-Cox impregnations of layer IV stellate cell dendritic fields were analysed and total neuronal and glial counts were also done within layer IV of the primary visual cortex. Normal visual stellate cell dendritic fields were radially organised, with the highest dendritic density being recorded below the soma. In short term visually deprived animals and in the exposed only for 21 dpp and then reared in light until 40 dpp the radial distribution of dendrites was maintained but the peak density shifted to above the soma. In all other experimental groups this abnormal polarisation was still present but not as marked. Measurement of branching indices suggested that these field changes resulted from increased branching and growth in the superficial domain and not from the reorientation of dendrites. Differential glial counts revealed a significantly higher number of microglia in dark reared animals than in controls. Neuronal numbers were not affected.

Animals↗
PubMed1988

Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation.

In the mammalian cerebral cortex, neurons in a given layer are generated at about the same time in development. These cells also tend to share similar sets of morphological and physiological properties and have projection patterns characteristic of that layer. This correspondence between the birthday and eventual fate of a cortical neuron suggests the possibility that the commitment of a cell to a particular laminar position and set of connections may occur very early on in cortical development. The experiments described here constitute an attempt to manipulate the fates of newly generated cortical neurons upon transplantation. The first set of experiments addressed the normal development of neurons in the primary visual cortex (area 17) of the ferret. Injections of 3H-thymidine into newborn ferrets showed that neurons generated after birth are destined to sit in layer 2/3 of the cortex, whereas neurons born on embryonic day (E) 32 populate primarily layers 5 and 6. Many layer 2/3 neurons in adult ferrets could be retrogradely labeled with HRP from visual cortical areas 18 and 19, while about half of the neurons in layer 6 were found to project to the lateral geniculate nucleus (LGN). In the second set of experiments, presumptive layer 2/3 cells were labeled in vivo by injecting ferrets with 3H-thymidine on P1 and P2. Before the cells had a chance to migrate, they were removed from the donor brain, incubated in a fluorescent dye (DAPI or fast blue), and dissociated into a single-cell suspension. The labeled cells were then transplanted into the proliferative zone of a littermate host ferret ("isochronic" transplants). Over the next few weeks, many of these dye-labeled cells underwent changes in their position and morphology that were consistent with a radially directed migration and subsequent differentiation into cortical neurons. The final positions of isochronically transplanted neurons in the host brain were mapped out by using the 3H-thymidine marker after long survival periods. About 97% of radioactively labeled cells had migrated out into the visual cortex, where they attained a compact laminar distribution: 99% were found in layer 2/3, their normal destination. The labeled cells had normal, mostly pyramidal neuronal morphologies and appeared to be well integrated with host neurons when viewed in Nissl-stained sections. Ten isochronically transplanted neurons were successfully labeled after HRP injection into 2 normal target regions, areas 18 and 19.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Excitatory-inhibitory network in the visual cortex: psychophysical evidence.

At early stages in visual processing cells respond to local stimuli with specific features such as orientation and spatial frequency. Although the receptive fields of these cells have been thought to be local and independent, recent physiological and psychophysical evidence has accumulated, indicating that the cells participate in a rich network of local connections. Thus, these local processing units can integrate information over much larger parts of the visual field; the pattern of their response to a stimulus apparently depends on the context presented. To explore the pattern of lateral interactions in human visual cortex under different context conditions we used a novel chain lateral masking detection paradigm, in which human observers performed a detection task in the presence of different length chains of high-contrast-flanked Gabor signals. The results indicated a nonmonotonic relation of the detection threshold with the number of flankers. Remote flankers had a stronger effect on target detection when the space between them was filled with other flankers, indicating that the detection threshold is caused by dynamics of large neuronal populations in the neocortex, with a major interplay between excitation and inhibition. We considered a model of the primary visual cortex as a network consisting of excitatory and inhibitory cell populations, with both short- and long-range interactions. The model exhibited a behavior similar to the experimental results throughout a range of parameters. Experimental and modeling results indicated that long-range connections play an important role in visual perception, possibly mediating the effects of context.

Feedback↗
PubMed1997

Immunocytochemical localization of calcium-binding protein calretinin containing neurons in cat visual cortex.

The distribution and morphology of neurons containing calretinin in area 17 of the cat visual cortex were studied. The calcium-binding protein calretinin was localized by antibody immunocytochemistry. Most of the calretinin-labeled neurons were located in layers I, II, and III. There were few calretinin-labeled cells in the other layers. The labeled neurons varied in morphology. The majority of the labeled neurons had small round or oval somas with long processes traveling perpendicular to the pial surface. Many small multipolar neurons were also labeled by this antibody. These results indicate that the calcium-binding protein calretinin is contained both in specific layers and selective cell types in the cat primary visual cortex.

Animals↗
PubMed2005

Evaluation of extraocular electrodes for a retinal prosthesis using evoked potentials in cat visual cortex.

OBJECTIVE: To assess the efficacy of a device using extraocular electrodes as a retinal prosthesis by evaluating the responses evoked in the visual cortex to electrical stimulation. METHODS: In anaesthetised cats, a lateral orbital dissection and ipsilateral parietal craniotomy was performed. Two extraocular retinal prosthesis (ERP) disc electrodes were sutured to the sclera on the lateral and superior aspects of the globe. Retinal stimulation was performed with charge-balanced constant-current pulses. Potentials evoked in the visual cortex were measured with a ball electrode placed on the lateral gyrus after removal of the dura. RESULTS: Stable attachment of the ERP electrodes to the globe was achieved with scleral sutures. Visual cortex responses were recorded with the electrodes in bipolar and monopolar configurations. The evoked response consisted of an early component with a peak around 8 ms, and a late component with a peak after 50 ms. Thresholds for evoking a response occurred at current intensities as low as 500 microA. Through extrapolation from evoked response amplitude data, thresholds as low as 300 microA were calculated. Cathodal monopolar stimulation demonstrated lower thresholds than anodal stimulation for evoking cortical responses. CONCLUSIONS: The ERP electrodes can be easily attached to the globe and are effective in electrically stimulating the retina, evoking responses in the primary visual cortex. Threshold charge-density was within safe limits for neural stimulation.

Animals↗
PubMed2006

Reduced functional activation after fatiguing exercise is not confined to primary motor areas.

We have previously shown that following a period of unimanual fatiguing exercise, there is a reduction in primary sensorimotor cortex (SM1) activation with movement of either the fatigued or the non-fatigued hand by Benwell et al. (Exp Brain Res 167:160-164, 2005). In the present study we have investigated whether this reduction is confined to motor areas or is more widespread. Functional imaging was performed before and after a 10-minute fatiguing exercise of the left hand (30% of maximum handgrip strength) in seven normal subjects (4 M, mean age 25 years). The activating task was a handgrip against a low resistance (1 kg) in response to a visual cue (chequerboard reversal every 2 +/- 0.5 s). We compared activation in SM1, supplementary motor area (SMA), cerebellum (CB) and primary visual cortex (V1) before and after the fatiguing exercise. After exercise, contralateral SM1 activation was reduced by 33% (P < 0.05) compared to baseline for the fatigued hand and by 49% for the non-fatigued hand (P < 0.05). A similar pattern was seen for the bilateral SMA and ipsilateral CB following exercise (45 vs. 50% for SMA; 30 vs. 35% for CB; fatigued versus non-fatigued). Activation was also reduced in V1 but to a lesser extent than in motor areas (19 vs. 24%; fatigued versus non-fatigued). These results show that although the reduced functional activation during the recovery period after fatiguing exercise is more marked in motor areas, it also extends to non-motor areas such as the visual cortex, suggesting that there are more widespread changes in cerebral haemodynamic responses after fatigue.

Adult↗
PubMed2002

Pale cytochrome oxidase stripes in V2 receive the richest projection from macaque striate cortex.

Once the visual pathway reaches striate cortex, it fans out to a number of extrastriate areas. The projections to the second visual area (V2) are known to terminate in a patchy manner. V2 contains a system of repeating pale-thin-pale- thick stripes of cytochrome oxidase (CO) activity. We examined whether the patchy terminal fields arising from primary visual cortex (V1) projections are systematically related to the CO stripes in V2. Large injections of an anterograde tracer, [(3)H]proline, were made into V1 of both hemispheres in 5 macaques. The resulting V2 label appeared in layers 2-6, with the densest concentration in layer 4. In 21/29 injections, comparison of adjacent flatmount sections processed either for autoradiography or CO activity showed that the heaviest [(3)H]proline labeling was located in pale CO stripes. In 7/29 injections, there was no clear enrichment of labeling in the CO pale stripes. In 1 injection, the proline label correlated with dark CO stripes. On a fine scale, CO levels vary within V2 stripes, giving them an irregular, mottled appearance. In all stripe types, the density of proline label would often wax and wane in opposing contrast to these local fluctuations in CO density. Our data showed that V1 input is generally anti-correlated with the intensity of CO staining in V2, with strongest input to pale stripes. It is known that the pulvinar projects preferentially to dark stripes. Therefore, V2 receives interleaved projections from V1 and the pulvinar. Because these projections favor different stripe types, they may target separate populations of neurons.

Animals↗
PubMedDate not supplied

Deterministic dynamics emerging from a cortical functional architecture.

Cerebral cortex has a range of interconnected functional architectures. Some appear random and without structure, while others are geometrical. Although the biological details certainly constrain spatial temporal patterns in neural networks, the influence that the laws of deterministic dynamics bring to bear on even isolated simple geometries are unknown. Layer II/III of primary visual cortex has long range horizontal connections with projections to and from other layers. The long range excitatory connections were modeled in isolation as an isolated laterally connected functional architecture. The Hodgkin-Huxley or Pinsky-Rinzel equations were used to simulate the neuronal elements. Waves of activity could propagate through the functional architecture; depending on the synaptic kinetics, the system could settle down into quiescence, oscillations, or seemingly random behavior. Order could be found in random-looking behavior by the application of techniques from chaos theory. Furthermore, the range and transitions of the temporal patterns in the modeled collection of neurons are similar to those found in other non-linear systems. The possibility that the temporal patterns of neurons in situ are also constrained by these mathematical laws is discussed.

Action Potentials↗
PubMedDate not supplied

Mapping human visual cortex with positron emission tomography.

Positron-emission tomography (PET) can localize functions of the human brain by imaging regional cerebral blood flow (CBF) during voluntary behaviour. Functional brain mapping with PET, however, has been hindered by PET's poor spatial resolution (typically greater than 1 cm). We have developed an image-analysis strategy that can map functional zones not resolved by conventional PET images. Brain areas selectively activated by a behavioural task can be isolated by subtracting a paired control-state image from the task-state image, thereby removing areas not recruited by the task. When imaged in isolation the centre of an activated area can be located very precisely. This allows subtle shifts in response locale due to changes in task to be detected readily despite poor spatial resolution. As an initial application of this strategy we mapped the retinal projection topography of human primary visual cortex. Functional zones separated by less than 3 mm (centre-to-centre) were differentiated using PET CBF images with a spatial resolution of 18 mm. This technique is not limited to a particular brain area or type of behaviour but does require that the increase in CBF produced by the task be both intense and focal.

Cerebrovascular Circulation↗
PubMed2007

[Parallel processing of motion vision].

Several neuropsychological studies have reported dissociation between motion vision and object vision. One patient with motion blindness had a bilateral MT/V5 lesion and could see objects, but could not see the motion of the objects (Zihl et al, 1983). By contrast, some blindsight patients with primary visual cortex lesions cannot see objects but can see their movement (e.g. Riddoch, 1917). These results imply that movement vision and form vision rely on independent mechanisms. However one patient with motion blindness had controversial symptoms concerning motion vision. She could not perceive the movement of objects, although she could walk without colliding with obstacles and could catch incoming objects. It has also been reported that patients with a bilateral parietal lesion had well-preserved primary motion vision, but had problems walking and catching a ball (Vaina, 1998). Therefore, motion for vision and motion for action might have independent mechanisms. Such dissociation has also been noted in patients with Bálint syndrome. Some patients behave like a blind person but can walk and catch a ball, while other patients bump into obstacles while walking. These results indicate that the neural bases of motion vision are distinct from those of form vision and that there are subdivisions of motion vision.

Agnosia↗
PubMed1999

Long term depression is expressed during postnatal development in rat visual cortex: a role for visual experience.

Long term forms of synaptic plasticity and in particular LTD/LTP are both present in the mammalian visual cortex. However, while LTP is not inducible in adulthood LTD can be elicited in the mature brain, but its developmental pattern is unknown. Aim of this work was to investigate whether LTD is expressed during postnatal development and if it is modulated by visual experience. To investigate these points we have used rat primary visual cortex slices taken at different stages of functional maturation process, i.e., postnatal day 17 (P17), P23 and P30-35. LTD was assessed by measuring the amplitude of extracellular field potentials recorded in cortical layers 2/3 and elicited by low frequency stimulation to the white matter. LTD was expressed at all ages investigated without significant differences between age groups. These data indicate that LTD developmental expression is not temporally related with the period of functional maturation of rat visual cortex. Dark rearing from birth to P23 resulted in a reduction of LTD amplitude while light deprivation from P17 to P30 did not affect LTD expression in comparison to age matched control values. We suggest that light imprinting is essential for a normal LTD expression during postnatal development.

Animals↗
PubMed1992

Pathfinding and target selection by developing geniculocortical axons.

During development of the mammalian cerebral cortex, thalamic axons must grow into the telencephalon and select appropriate cortical targets. In order to begin to understand the cellular interactions that are important in cortical target selection by thalamic axons, we have examined the morphology of axons from the lateral geniculate nucleus (LGN) as they navigate their way to the primary visual cortex. The morphology of geniculocortical axons was revealed by placing the lipophilic tracer Dil into the LGN of paraformaldehyde-fixed brains from fetal and neonatal cats between embryonic day 26 (E26; gestation is 65 d) and postnatal day 7 (P7). This morphological approach has led to three major observations. (1) As LGN axons grow within the intermediate zone of the telencephalon toward future visual cortex (E30-40), many give off distinct interstitial axon collaterals that penetrate the subplate of nonvisual cortical areas. These collaterals are transient and are not seen postnatally. (2) There is a prolonged period during which LGN axons are restricted to the visual subplate prior to their ingrowth into the cortical plate; the first LGN axons arrive within visual subplate by E36 but are not detected in layer 6 of visual cortex until about E50. (3) Within the visual subplate, LGN axons extend widespread terminal branches. This represents a marked change in their morphology from the simple growth cones present earlier as LGN axons navigate en route to visual cortex. The presence of interstitial collaterals suggests that there may be ongoing interactions between LGN axons and subplate neurons along the entire intracortical route traversed by the axons. From the extensive branching of LGN axons within the visual subplate during the waiting period, it appears that they are not simply "waiting." Rather, LGN axons may participate in dynamic cellular interactions within the subplate long before they contact their ultimate target neurons in layer 4. These observations confirm the existence of a prolonged waiting period in the development of thalamocortical connections and provide important morphological evidence in support of the previous suggestion that interactions between thalamic axons and subplate neurons are necessary for cortical target selection.

Aging↗
PubMed1991

Significant non-serotonergic raphe projection to the visual cortex of the rat. An immunohistochemical study combined with retrograde tracing.

The present study investigated the distribution of serotonergic and non-serotonergic raphe neurons with direct projections to the visual cortex. The study employed the WGA-apoHRP-Au retrograde transport technique combined with 5-HT immunohistochemical staining. Retrogradely labeled cells were observed in the dorsal raphe nucleus, the median raphe nucleus, and in the B9 and B6 cell groups. One notable finding was the great number of retrogradely labeled, non-5-HT immunoreactive cells. The average percentages of such cells in the various raphe regions were as follows: DR: 52% (n = 401); MR: 35% (n = 311); B9: 24% (n = 129); B6: 95% (n = 200). The present study demonstrated the presence of a significant proportion of non-serotonergic raphe region neurons projecting to the primary visual cortex in the rat. It is suggested that these neurons may complement the aminergic neurons as part of the ascending system which controls the functions of the visual cortex.

Animals↗
PubMed1996

Distribution and localization of NMDA receptor subunit 1 in the visual cortex of strabismic and anisometropic amblyopic cats.

ACTIVATION of NMDA (N-methyl-D-aspartate) receptors has recently been proposed as a prerequisite for the induction of experience-dependent modification of visual cortical neurones seen during early postnatal development. A new monoclonal antibody to the NMDA receptor subunit 1 (NMDA-R1) has been used to localize and compare the distribution of the receptors in the primary visual cortex of normal cats and those raised with either amblyopia induced by monocular optical blur or monocular esotropic strabismus. Although all three groups showed densest labelling in layers II-III, a comparison of immunopositive cells at any depth below the cortical surface showed a significantly lower frequency in strabismic and anisometropic cats than in normal cats, but a greater frequency in anisometropic cats that in strabismic animals. There appears to be no direct relationship between the expression of NMDA-R1 receptors and the level of excitability, binocularity or neuronal acuity known to exist in either of these two cat models of amblyopia, thus raising further questions as to the precise nature of the role of NMDA receptors in the processes of visual cortical plasticity.

Amblyopia↗