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PubMedDate not supplied

What has intrinsic signal optical imaging taught us about NGF-induced rapid plasticity in adult cortex and its relationship to the cholinergic system?

Intrinsic signal optical imaging (ISI) is a high-resolution functional brain mapping technique that is being used to further our understanding of the neocortex and its interaction with drugs. Recent studies using combination ISI and in vivo pharmacology have advanced our insight into the actions of both acetylcholine and neurotrophins on inducing rapid and large-scale cortical plasticity. In particular, it appears that acetylcholine (ACh), nicotinic ACh receptors, nerve growth factor (NGF), and NGF receptors (TrkA and p75) are involved in an important feedback loop between the basal forebrain cholinergic system (BFCS) and the neocortex. Specifically, recent data suggest that NGF expressed in the cortex may act on multiple time scales on the BFCS: acutely to increase BFCS release of acetylcholine, intermediately to induce sprouting of BFCS axons, and long-term to change gene expression of BFCS neurons. In this article, advances in understanding the links in vivo between the BFCS, neocortex, nicotinic ACh receptors, and NGF are reviewed.

Acetylcholine↗
PubMed1998

Optical imaging and electrophysiology of rat barrel cortex. II. Responses to paired-vibrissa deflections.

A study was undertaken to investigate the response of the rodent somatosensory barrel cortex to paired-whisker stimuli. Cortical responses to controlled whisker deflections were recorded by (i) conventional multi-unit extracellular recording within the cytochrome oxidase rich barrels centers, and (ii) intrinsic signal optical imaging, a technique that measures an optical correlate of neuronal activity thought to be related to the deoxygenation of hemoglobin in activated regions. Stimuli were applied to two whiskers in sequence, at temporal separations ranging from 0 to 60 ms. Over intervals of 10-40 ms, the primary effect of paired-whisker stimulation was suppressive. We suggest that paired-whisker inhibition results from the activation of layer IV fast-spike units within the principle whisker's barrel, by excitatory input arriving from a surround-whisker. Paired-whisker stimulation produces inhibition in intrinsic images, because it results in a net reduction in layer II/III and/or layer IV metabolism. Intra-cortical inhibition may serve to convert the sequence of inputs from the whisker array into a barrel cortex magnitude code that can be read by higher cortical areas.

Animals↗
PubMed1996

Functional parasagittal compartments in the rat cerebellar cortex: an in vivo optical imaging study using neutral red.

1. The spatial patterns of activation in the rat cerebellar cortex evoked by peripheral stimulation were studied in vivo using optical imaging techniques. 2. Crus I and Crus II were stained with the pH sensitive dye, neutral red. Electrical stimulation of the vibrissae area of the ipsilateral face evoked optical responses consisting of parasagittal bands. The bands were 100-300 microns in width, elongated in the anterior-posterior direction, commonly extended across at least two folia, and varied in number from 1 to 7. 3. The optical responses were dependent on activation of postsynaptic elements since they were decreased substantially by the non-N-methyl-D-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. The optical bands were shown to correspond anatomically with the parasagittal compartments revealed by immunostaining with anti-zebrin II. 4. The present study demonstrates that functional parasagittal compartments exist in the rat cerebellar cortex and suggests that zebrin-positive Purkinje cell subgroups are anatomically related to this functional organization.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2004

Multiple passages of light through an absorption inhomogeneity in optical imaging of turbid media.

Multiple passages of light through an absorption inhomogeneity of finite size deep within a turbid medium are analyzed for optical imaging by use of the self-energy diagram. The nonlinear correction becomes more important for an inhomogeneity of a larger size and with greater contrast in absorption with respect to the host background. The nonlinear correction factor agrees well with that from Monte Carlo simulations for cw light. The correction is approximately 50%-75% in the near infrared for an absorption inhomogeneity with the typical optical properties found in tissues and five times the size of the transport mean free path.

Light↗
PubMed1997

Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging.

Odors are thought to be represented by a distributed code across the glomerular modules in the olfactory bulb (OB). Here, we optically imaged presynaptic activity in glomerular modules of the zebrafish OB induced by a class of natural odorants (amino acids [AAs]) after labeling of primary afferents with a calcium-sensitive dye. AAs induce complex combinatorial patterns of active glomerular modules that are unique for different stimuli and concentrations. Quantitative analysis shows that defined molecular features of stimuli are correlated with activity in spatially confined groups of glomerular modules. These results provide direct evidence that identity and concentration of odorants are encoded by glomerular activity patterns and reveal a coarse chemotopic organization of the array of glomerular modules.

Amino Acids↗
PubMed2005

Development of a microfluidic platform with an optical imaging microarray capable of attomolar target DNA detection.

In this paper, DNA hybridization in a microfluidic manifold is performed using fluorescence detection on a fiber-optic microarray. The microfluidic device integrates optics, sample transport, and fluidic interconnects on a single platform. A high-density optical imaging fiber array containing oligonucleotide-labeled microspheres was developed. DNA hybridization was observed at concentrations as low as 10 aM with response times of less than 15 min at a flow rate of 1 microL/min using 50 microL of target DNA samples. The fast response times coupled with the low sample volumes and the use of a high-density, fiber-optic microarray format make this method highly advantageous. This paper describes the initial development, optimization, and integration of the microfluidic platform with imaging fiber arrays.

Bacillus thuringiensis↗
PubMed2006

Extended resolution wide-field optical imaging: objective-launched standing-wave total internal reflection fluorescence microscopy.

Standing-wave total-internal-reflection fluorescence (SW-TIRF) microscopy uses a super-diffraction-limited standing evanescent wave to extract the high-spatial-frequency content of an object through a diffraction-limited optical imaging system. The effective point-spread function is better than a quarter of the emission wavelength. With a 1.45 numerical aperture objective and 532 nm excitation wavelength, a Rayleigh resolution of approximately 100 nm can be achieved, which is better than twice the resolution of conventional TIRF microscopy. This first experimental realization of SW-TIRF in an objective-launched geometry demonstrates the potential for extended resolution imaging at high speed by using wide-field microscopy.

Equipment Design↗
PubMed2002

[Near-infrared optical imaging of human brain function--a novel approach to the brain and the mind].

Near-infrared spectroscopy (NIRS) can measure changes in the hemoglobin oxygenation state in the human brain. NIRS has been oriented toward use for clinical monitoring of tissue oxygenation. However, we and others have recently demonstrated that NIRS also has the potential for neuroimaging. NIRS instruments, which use continuous wave light (CW) as a light source, are now commercially available. These CW-type NIRS instruments have high temporal resolution (less than 1 second) and allow long-term and continuous measurements, though they do not provide absolute values of changes in hemoglobin concentrations. In contrast, time-resolved spectroscopy (TRS), which uses short pulsed laser diodes as light sources, makes quantification possible. Quantification is necessary for the imaging of brain activity. Topographical images can be obtained by the use of our recently developed 64-channel time-resolved optical tomographic imaging system (optical CT) or by combining the 1 channel TRS instrument with the multichannel CW-type NIRS instrument. NIRS is completely non-invasive and does not require strict motion restriction during measurements unlike PET and fMRI. It is, thus, expected that NIRS will open a window into brain physiology in subjects who are difficult to examine with PET and fMRI such as children, the elderly, and patients with psychoneurological problems.

Brain↗
PubMed2005

Dispersion control with a Fourier-domain optical delay line in a fiber-optic imaging interferometer.

Recently, Fourier-domain (FD) optical delay lines (ODLs) were introduced for high-speed scanning and dispersion compensation in imaging interferometry. We investigate the effect of first- and second-order dispersion on the photocurrent signal associated with an optical coherence imaging system implemented with a single-mode fiber, a superluminescent diode centered at 950 nm +/- 35 nm, a FD ODL, a mirror, and a layered LiTAO3 that has suitable dispersion characteristics to model a skin specimen. We present a practical and useful method to minimize the effect of dispersion through the interferometer and the specimen combined, as well as to quantify the results using two general metrics for resolution. Theoretical and associated experimental results show that, under the optimum solution, the maximum broadening of the point-spread function through a 1-mm-deep specimen is limited to 57% of its original rms width value (i.e., 8.1 microm optimal, 12.7 microm at maximum broadening) compared with approximately 110% when compensation is performed without the specimen taken into account.

Animals↗
PubMed2004

Optical imaging of binaural interaction in multiple fields of the guinea pig auditory cortex.

Locating the source of a sound is an important function of the auditory system and interaural intensity differences are one of the most important cues. To study the functional pathways of sound localisation processing in the auditory cortex, activity in multiple fields of the guinea pig auditory cortex during stimulation with interaural intensity differences was studied using optical imaging with a voltage-sensitive dye. Of the auditory core (primary and dorsocaudal) and the belt fields which surround them, the posterior and ventroposterior belt fields were the most sensitive to interaural intensity differences. This suggests that the caudal pathway of the auditory cortex is involved in sound localisation.

Acoustic Stimulation↗
PubMed2004

Functional glutamatergic and glycinergic inputs to several superior olivary nuclei of the rat revealed by optical imaging.

Superior olivary complex (SOC) neurons receive excitatory and inhibitory inputs from both ears. We determined the nature of such inputs to the main SOC nuclei with an optical imaging system. To do so, brainstem slices of postnatal (P) rats (P3-13) were treated with the fast voltage-sensitive dye RH795, and ipsilateral and contralateral SOC inputs were activated electrically. Optical signals, equivalent to membrane potential changes, were detected by a 464-photodiode array. The signals consisted mostly of two components which were identified as pre- and postsynaptic potentials in experiments with Ca2+-free solutions. They correlated with morphological structures, i.e. the presynaptic components were prominent in neuropil regions whereas the postsynaptic components dominated in somata regions. Postsynaptic components were distinguished pharmacologically with the glycine receptor blocker strychnine and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Concerning the lateral superior olive, we confirmed the known glutamatergic inputs from the ipsilateral side and the glycinergic inputs from the ipsilateral and contralateral sides. Furthermore, we identified a CNQX-sensitive input from the contralateral side. In the medial superior olive, we corroborated the glutamatergic and glycinergic inputs from the ipsilateral and contralateral sides. Both ipsi- and contralaterally, the glutamatergic input was more pronounced than the glycinergic input. In the superior paraolivary nucleus, we also identified ipsilateral and contralateral inputs. Besides the known glycinergic input from the contralateral side, we found a novel glycinergic input from the ipsilateral side and identified CNQX-sensitive inputs from the contralateral and ipsilateral sides. The latter was very weak and appeared only in 30% of the experiments. The data show the feasibility of identifying functional inputs to the SOC with voltage-sensitive dye recordings.

Animals↗
PubMed2006

Effective scattering coefficient of the cerebral spinal fluid in adult head models for diffuse optical imaging.

An efficient computation of the time-dependent forward solution for photon transport in a head model is a key capability for performing accurate inversion for functional diffuse optical imaging of the brain. The diffusion approximation to photon transport is much faster to simulate than the physically correct radiative transport equation (RTE); however, it is commonly assumed that scattering lengths must be much smaller than all system dimensions and all absorption lengths for the approximation to be accurate. Neither of these conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight distances in the CSF are small, of the order of a few millimeters, we explore the idea that the CSF scattering coefficient may be modeled by any value from zero up to the order of the typical inverse line-of-sight distance, or approximately 0.3 mm(-1), without significantly altering the calculated detector signals or the partial path lengths relevant for functional measurements. We demonstrate this in detail by using a Monte Carlo simulation of the RTE in a three-dimensional head model based on clinical magnetic resonance imaging data, with realistic optode geometries. Our findings lead us to expect that the diffusion approximation will be valid even in the presence of the CSF, with consequences for faster solution of the inverse problem.

Adult↗
PubMed1998

Role of NMDA receptors in the propagation of excitation in rat visual cortex as studied by optical imaging.

To examine the role of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in the propagation of information in visual cortex, optical imaging with high spatial and temporal resolution of neuronal activity was used in cortical slices of rats. Single-shock stimulation of the white matter elicited a vertical propagation of excitation toward the cortical surface simultaneously with a horizontal spread of excitation in lower layers. The horizontal spread in upper layers occurred subsequent to the vertical spread reaching these layers. The results from perfusion of Ca2+-free medium and application of an antagonist of non-NMDA receptors indicated that this intracortical propagation of signals is due mostly, if not exclusively, to the postsynaptic excitation of cortical neurons. Blockade of NMDA receptors attenuated the rising and peak phases of the upper horizontal spread, but did not affect those of the lower horizontal or vertical propagation of excitation. Perfusion with Mg2+-free solution enhanced the upper horizontal spread, but in most cases did not significantly change the spread of excitation in the other pathways. These results indicate that NMDA receptors are involved in the flow of information in the upper layers of visual cortex, and further suggest that this propagation of activity is mediated mainly by horizontal connections intrinsic to the upper layers.

2-Amino-5-phosphonovalerate↗
PubMed2005

Spatial analysis of spike-timing-dependent LTP and LTD in the CA1 area of hippocampal slices using optical imaging.

Spike-timing-dependent long-term potentiation (LTP) and long-term depression (LTD) were investigated in the CA1 area of hippocampal slices using optical imaging. A pair of electrical pulses were used to stimulate the Schaffer-commissural collateral and the stratum oriens with various sets of relative timing (tau) between the two stimuli. These sets of paired pulses gave rise to LTP/LTD, whose induction was closely related to tau, and their profiles were classified into two types depending on their layer specific location along the dendrite. One was characterized by a symmetric time window observed in the proximal region of the stratum radiatum (SR) and the other by an asymmetric time window in the distal region of the SR. Bath application of bicuculline (gamma-aminobutyric acid [GABA] receptor antagonist) to hippocampal slices revealed that GABAergic interneuron projections were responsible for the symmetry of a time window.

Action Potentials↗
PubMed2000

Optical imaging of bilingual cortical representations. Case report.

The organization of language in the brains of multilingual persons remains controversial. The authors investigated language representations in a proficient bilingual patient by using a novel neuroimaging technique, intraoperative optical imaging of intrinsic signals (iOIS), and a visual object naming task. The results indicate that there are cortical areas that are activated by the use of both English and Spanish languages (superior temporal sulcus, superior and middle temporal gyri, and parts of the supramarginal gyrus). In addition, language-specific areas were identified in the supramarginal (Spanish) and precentral (English) gyri. These results suggest that cortical language representations in bilingual persons may consist of both overlapping and distinct components. Furthermore, this study demonstrates the utility of iOIS in detecting topographical segregation of cognitively distinct cortices.

Adult↗
PubMed2002

Calcium-induced alterations in mitochondrial morphology quantified in situ with optical scatter imaging.

Optical scatter imaging (OSI), a technique we developed recently, was used to measure the ratio of wide-to-narrow angle scatter (OSIR) within endothelial cells subjected to calcium overload (1.6 mM) after permeabilization by ionomycin. Within a few minutes of calcium overload, the mitochondria, which started as elongated organelles, rounded up into spherically shaped particles. This change in morphology was accompanied by a statistically significant 14% increase in OSIR in the cells' cytoplasm. Mitochondrial rounding and OSIR increase were suppressed by cyclosporin A (25 microM), implying that the observed geometrical and scattering changes were directly attributable to the mitochondrial permeability transition. The angular scattering properties of a long mitochondrion rounding up were approximated by numerical simulations of light scatter from an ellipsoid rounding up into a sphere. The simulations predicted a relative increase in OSIR comparable to that measured experimentally for the case where the shape transition takes place with little or no volume increase. The simulations also suggested that mitochondrial refractive index changes could not account for the OSIR changes observed. Our data show that changes in OSIR correlate with mitochondrial morphology change in situ. OSI provides a new tool for subcellular imaging and complements other microscopy methods, such as fluorescence.

Animals↗
PubMed2003

Spatiotemporal characteristics of cerebral blood volume changes in rat somatosensory cortex evoked by sciatic nerve stimulation and obtained by optical imaging.

The spatiotemporal characteristics of changes in cerebral blood volume associated with neuronal activity were investigated in the hindlimb somatosensory cortex of alpha-chloralose-urethane anesthetized rats (n=10) with optical imaging at 570 nm through a thinned skull. Activation of the cortex was carried out by electrical stimulation of the contralateral sciatic nerve with 5-Hz, 0.3-V pulses (0.5 ms) for 2 s. The stimulation evoked a monophasic decrease in optical reflectance at the cortical parenchyma and arterial sites soon after the onset of stimulation, whereas no similar response was observed at vein compartments. The optical signal changes reached 10% of the peak response 0.70 +/- 0.32 s after the start of stimulation, and no significant time lag in this 10% start latency time was observed between the response at the cortical parenchyma and artery compartments. The decrease in optical reflectance reached a peak (0.25 +/- 0.047%) 2.66 +/- 0.61 s after stimulus onset at parenchymal sites, which is 0.40 +/- 0.20 s earlier (P<0.05) than that at arterial sites (0.50 +/- 0.068% 3.06 +/- 0.70 s). Varying the locations within the cortical parenchyma and arterial compartments did not significantly affect the temporal characteristics of the evoked signal. These results suggest that stimulation of the sciatic nerve evokes an increase in local blood volume in both capillaries (cortical parenchyma) and arterioles soon after the onset of a stimulus, but the blood volume increase evoked in capillaries could not be entirely accounted for by the dilation of arterioles.

Animals↗