Search PubMed⌕ Search

Biomedical subjects

A Grinvald

Publications and source records attributed to A Grinvald.

At least 37 records · Page 2Linked to original sources
PubMed1994

Optical imaging reveals the functional architecture of neurons processing shape and motion in owl monkey area MT.

We have used optical imaging based on intrinsic signals to explore the functional architecture of owl monkey area MT, a cortical region thought to be involved primarily in visual motion processing. As predicted by previous single-unit reports, we found cortical maps specific for the direction of moving visual stimuli. However, these direction maps were not distributed uniformly across all of area MT. Within the direction-specific regions, the activation produced by stimuli moving in opposite directions overlapped significantly. We also found that stimuli of differing shapes, moving in the same direction, activated different cortical regions within area MT, indicating that direction of motion is not the only parameter according to which area MT of owl monkey is organized. Indeed, we found clear evidence for a robust organization for orientation in area MT. Across all of MT, orientation preference changes smoothly, except at isolated line- or point-shaped discontinuities. Generally, paired regions of opposing direction preference were encompassed within a single orientation domain. The degree of segregation in the orientation maps was 3-5 times that found in direction maps. These results suggest that area MT, like V1 and V2, has a rich and multidimensional functional organization, and that orientation, a shape variable, is one of these dimensions.

Animals↗
PubMed1994

Cortical point-spread function and long-range lateral interactions revealed by real-time optical imaging of macaque monkey primary visual cortex.

Processing of retinal images is carried out in the myriad dendritic arborizations of cortical neurons. Such processing involves complex dendritic integration of numerous inputs, and the subsequent output is transmitted to multiple targets by extensive axonal arbors. Thus far, details of this intricate processing remained unexaminable. This report describes the usefulness of real-time optical imaging in the study of population activity and the exploration of cortical dendritic processing. In contrast to single-unit recordings, optical signals primarily measure the changes in transmembrane potential of a population of neuronal elements, including the often elusive subthreshold synaptic potentials that impinge on the extensive arborization of cortical cells. By using small visual stimuli with sharp borders and real-time imaging of cortical responses, we found that shortly after its onset, cortical activity spreads from its retinotopic site of initiation, covering an area at least 10 times larger, in upper cortical layers. The activity spreads at velocities from 100 to 250 microns/msec. Near the V1/V2 border the direct activation is anisotropic and we detected also anisotropic spread; the "space constant" for the spread was approximately 2.7 mm parallel to the border and approximately 1.5 mm along the perpendicular axis. In addition, we found cortical interactions between cortical activities evoked by a small "center stimulus" and by large "surround stimuli" positioned outside the classical receptive field. All of the surround stimuli used suppressed the cortical response to the center stimulus. Under some stimulus conditions iso-orientation suppression was more pronounced than orthogonal-orientation suppression. The orientation dependence of the suppression and its dependency on the size of some specific stimuli indicate that at least part of the center surround inhibitory interaction was of cortical origin. This findings reported here raise the possibility that distributed processing over a very large cortical area plays a major role in the processing of visual information by the primary visual cortex of the primate.

Animals↗
PubMed1993

Relationship between intrinsic connections and functional architecture revealed by optical imaging and in vivo targeted biocytin injections in primate striate cortex.

In primate primary visual cortex, neurons sharing similar response properties are clustered together forming functional domains that appear as a mosaic of patches or bands, often traversing the entire cortical depth from the pia to the white matter. Similarly, each cortical site connects laterally through an extensive network of intrinsic projections that are organized in multiple clusters (patches) and reach distances of up to a few millimeters. The relationship between the functional domains and these laterally connected patches has remained a controversial issue despite intensive research efforts. To investigate this relationship, we obtained high-resolution functional maps of the cortical architecture by in vivo optical imaging. Subsequently, extracellular injections of the sensitive anterograde tracer biocytin were targeted into selected functional domains. Within the ocular dominance system, we found that long-range intrinsic connections tended to link the monocular regions of same-eye ocular dominance columns. Furthermore, we discovered that binocular domains formed a separate set of connections in area V1; binocular regions were selectively connected among themselves but were not connected to strictly monocular regions, suggesting that they constitute a distinct columnar system. In the other subsystem subserving orientation preference, patches of intrinsic connections tended to link domains sharing similar orientation preferences. Analyses of the precision of these connections indicated that in both functional subsystems, < 15% of the connections were between domains having orthogonal response properties. However, their selectivity was limited; approximately 30% +/- 10% of the interconnected patches contained neurons exhibiting orientation tuning that differed from those found at the injection sites by at least 45 degrees. At short range (up to 400 microns from the injection site), this casual trend seemed markedly accentuated; the local, synaptic-rich axonal and dendritic arbors crossed freely through columns of diverse functional properties. These complex sets of connections can endow cortical neurons with a rich diversity of response properties and broad tuning.

Animals↗
PubMed1993

The layout of iso-orientation domains in area 18 of cat visual cortex: optical imaging reveals a pinwheel-like organization.

In this study we used optical imaging based on activity-dependent intrinsic signals to determine the distribution of cells responding to gratings of various orientations moving in different directions in area 18 of cat visual cortex. To test directional-selective clustering of neurons, we compared cortical activity maps obtained by stimulation with two gratings of identical orientation but moving in opposite directions. We found those maps to be almost identical, suggesting that neurons are not notably clustered into directionality columns. We also compared activity maps obtained with gratings of different orientations. Each of the orientation maps was similar to the 2-deoxyglucose maps previously reported. Having compiled the information obtained from the different orientations into one "orientation preference map," we found, in contrast to earlier reports, that iso-orientation domains are not elongated parallel bands but are small patches organized in "pinwheels" around points that we refer to as "orientation centers." We furthermore show that the only locations at which orientation preference changes rapidly are these orientation centers and not lines or loops. In addition, this report clarifies that our observations on the functional architecture of cat area 18, although at first sight at variance with earlier observations, are actually fully consistent with them. We therefore propose that in cat visual cortex pinwheel-like patterns of orientation preference form an irregular mosaic of modular units with an average density of 1.2 pinwheels per square millimeter.

Animals↗
PubMed1992

Relationships between orientation-preference pinwheels, cytochrome oxidase blobs, and ocular-dominance columns in primate striate cortex.

The relationships between cytochrome oxidase blobs, ocular-dominance columns, and iso-orientation domains, subsystems underlying visual perception, were explored in primary visual cortex of macaque monkey. High-resolution maps of these three subsystems were acquired. Optical imaging based on activity-dependent intrinsic signals revealed that the most prominent organizational feature of orientation preference was a radial arrangement, forming a pinwheel-like structure surrounding a singularity point. More than 80% of these pinwheels were centered along the midline of ocular-dominance columns. The iso-orientation contours of adjacent pinwheels crossed borders of ocular-dominance columns at approximately right angles. Pinwheels with the same or opposite directions of orientation-preference change were smoothly connected with each other. On the average, all orientations were equally represented. In exactly the same cortical area, the cytochrome oxidase blobs, thought to be involved in color processing, were also mapped, using cytochrome oxidase histology. Like the centers of pinwheels, the centers of blobs also lie along the midline of ocular-dominance columns. However, the centers of pinwheels did not coincide with the centers of blobs; these two subsystems are spatially independent. "Hypercolumn" modules, each including two complete pinwheels in two adjacent columns of complementary ocularity, as well as portions of a few blobs, were frequently found but did not seem to be the primary unit of cortical organization. An alternative to hypercolumns is proposed.

Animals↗
PubMed1992

Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception.

Long standing questions related to brain mechanisms underlying perception can finally be resolved by direct visualization of the architecture and function of mammalian cortex. This advance has been accomplished with the aid of two optical imaging techniques with which one can literally see how the brain functions. The upbringing of this technology required a multi-disciplinary approach integrating brain research with organic chemistry, spectroscopy, biophysics, computer sciences, optics and image processing. Beyond the technological ramifications, recent research shed new light on cortical mechanisms underlying sensory perception. Clinical applications of this technology for precise mapping of the cortical surface of patients during neurosurgery have begun. Below is a brief summary of our own research and a description of the technical specifications of the two optical imaging techniques. Like every technique, optical imaging also suffers from severe limitations. Here we mostly emphasize some of its advantages relative to all alternative imaging techniques currently in use. The limitations are critically discussed in our recent reviews. For a series of other reviews, see Cohen (1989).

Brain↗
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↗
PubMed1991

Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns.

The mammalian cortex is organized in a columnar fashion: neurons lying below each other from the pia to the white matter usually share many functional properties. Across the cortical surface, cells with similar response properties are also clustered together, forming elongated bands or patches. Some response properties, such as orientation preference in the visual cortex, change gradually across the cortical surface forming 'orientation maps'. To determine the precise layout of iso-orientation domains, knowledge of responses not only to one but to many stimulus orientations is essential. Therefore, the exact depiction of orientation maps has been hampered by technical difficulties and remained controversial for almost thirty years. Here we use in vivo optical imaging based on intrinsic signals to gather information on the responses of a piece of cortex to gratings in many different orientations. This complete set of responses then provides detailed information on the structure of the orientation map in a large patch of cortex from area 18 of the cat. We find that cortical regions that respond best to one orientation form highly ordered patches rather than elongated bands. These iso-orientation patches are organized around 'orientation centres', producing pinwheel-like patterns in which the orientation preference of cells is changing continuously across the cortex. We have also analysed our data for fast changes in orientation preference and find that these 'fractures' are limited to the orientation centres. The pinwheels and orientation centres are such a prominent organizational feature that it should be important to understand their development as well as their function in the processing of visual information.

Animals↗
PubMed1991

A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging.

The design of a macroscope constructed with photography lenses is described and several applications are demonstrated. The macroscope incorporates epi-illumination, a 0.4 numerical aperture, and a 40 mm working distance for imaging wide fields in the range of 1.5-20 mm in diameter. At magnifications of 1X to 2.5X, fluorescence images acquired with the macroscope were 100-700 times brighter than those obtained with commercial microscope objectives at similar magnifications. In several biological applications, the improved light collection efficiency (20-fold, typical) not only minimized bleaching effects, but, in concert with improved illumination throughput (15-fold, typical), significantly enhanced object visibility as well. Reduced phototoxicity and increased signal-to-noise ratios were observed in the in vivo real-time optical imaging of cortical activity using voltage-sensitive dyes. Furthermore, the macroscope has a depth of field which is 5-10 times thinner than that of a conventional low-power microscope. This shallow depth of field has facilitated the imaging of cortical architecture based on activity-dependent intrinsic cortical signals in the living primate brain. In these reflection measurements large artifacts from the surface blood vessels, which were observed with conventional lenses, were eliminated with the macroscope.

Animals↗
PubMed1990

Functional organization of primate visual cortex revealed by high resolution optical imaging.

A high spatial resolution optical imaging system was developed to visualize cerebral cortical activity in vivo. This method is based on activity-dependent intrinsic signals and does not use voltage-sensitive dyes. Images of the living monkey striate (VI) and extrastriate (V2) visual cortex, taken during visual stimulation, were analyzed to yield maps of the distribution of cells with various functional properties. The cytochrome oxidase--rich blobs of V1 and the stripes of V2 were imaged in the living brain. In V2, no ocular dominance organization was seen, while regions of poor orientation tuning colocalized to every other cytochrome oxidase stripe. The orientation tuning of other regions of V2 appeared organized as modules that are larger and more uniform than those in V1.

Action Potentials↗
PubMed1990

Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals.

We have shown previously the existence of small, activity-dependent changes in intrinsic optical properties of cortex that are useful for optical imaging of cortical functional architecture. In this study we introduce a higher resolution optical imaging system that offers spatial and temporal resolution exceeding that achieved by most alternative imaging techniques for imaging cortical functional architecture or for monitoring local changes in cerebral blood volume or oxygen saturation. In addition, we investigated the mechanisms responsible for the activity-dependent intrinsic signals evoked by sensory stimuli, and studied their origins and wavelength dependence. These studies enabled high-resolution visualization of cortical functional architecture at wavelengths ranging from 480 to 940 nm. With the use of near-infrared illumination it was possible to image cortical functional architecture through the intact dura or even through a thinned skull. In addition, the same imaging technique proved useful for imaging and discriminating sensory-evoked, activity-dependent changes in local blood volume and oxygen saturation (oxygen delivery). Illumination at 570 nm allowed imaging of activity-dependent blood volume increases, whereas at 600-630 nm, the predominant signal probably originated from activity-dependent oxygen delivery from capillaries. The onset of oxygen delivery started prior to the blood volume increase. Thus, optical imaging based on intrinsic signals is a minimally invasive procedure for monitoring short- and long-term changes in cerebral activity.

Animals↗
PubMed1987

Activity-dependent calcium transients in central nervous system myelinated axons revealed by the calcium indicator Fura-2.

Optical measurements from rat optic nerve, loaded with the new Ca2+ indicator Fura-2, provide the first evidence for the presence of activity-dependent fast intracellular [Ca2+] transients in mammalian central nervous system (CNS) myelinated axons. The results suggest that voltage-dependent Ca2+ channels are present in some of the myelinated axons. Optical measurements from axons stained with anterogradely transported voltage-sensitive dye suggest the presence of Ca2+-dependent potassium conductances in these axons. This report also demonstrates that Fura-2 can readily detect changes in [Ca2+] inside cells as a result of electrical activity, and establishes its suitability for measurements of intracellular Ca2+ transients in the millisecond time domain.

Animals↗
PubMed1987

Optical recording of synaptic potentials from processes of single neurons using intracellular potentiometric dyes.

To record post synaptic potentials or electrical activity from processes of single cells in a central nervous system (CNS) preparation in situ, voltage sensitive dyes can be injected intracellularly, thereby staining only the cell under investigation. We report the structure, evaluation, and synthesis of 11 fluorescent styryl dyes developed for iontophoretic injection. The optical signals that represent small synaptic potentials from single processes of iontophoretically injected cells are expected to be very small and, therefore, such measurements are not easy. We report the methodology that permitted the optical recording of action potentials from a 3-micron axon and the recording of small synaptic potentials from the processes of single cells in the segmental ganglia of the leech. The same dyes also proved useful for optical recording of action potentials of anterogradely labeled axons, following local extracellular injection at a remote site in a mammalian CNS preparation.

Action Potentials↗
PubMed1986

Ca2+- and K+-dependent communication between central nervous system myelinated axons and oligodendrocytes revealed by voltage-sensitive dyes.

The interactions between myelinated axons and surrounding glia cells, in rat optic nerve, were investigated by optical recording with voltage-sensitive dyes. Electrical stimulation of the nerve evoked an optical signal revealing two clearly distinct components: a fast propagating component, corresponding to the compound action potential, and a prominent slow component. Several lines of evidence suggest that part of the slow component originated from depolarization of the oligodendrocytes by potassium accumulation in the paranodal or internodal region. In addition, the experiments suggest that in this preparation axons also have voltage-dependent Ca2+ channels, and a Ca2+-dependent K+ conductance involved in the depolarization of oligodendrocytes. Thus, axons and oligodendrocytes communicate in an intimate, ionically-mediated fashion, and oligodendrocytes may play an important functional role beyond that of providing the myelin sheath.

Action Potentials↗