Search PubMed⌕ Search

Biomedical subjects

M Sur

Publications and source records attributed to M Sur.

At least 19 recordsLinked to original sources
PubMed1999

Stable properties of spontaneous EPSCs and miniature retinal EPSCs during the development of ON/OFF sublamination in the ferret lateral geniculate nucleus.

Retinal projections to the lateral geniculate nucleus (LGN) in ferrets progressively segregate into eye-specific laminae and subsequently into sublaminae that receive inputs from either ON-center or OFF-center afferents. To study the development of synaptic efficacy during a period of activity-dependent growth and reorganization in the CNS, we recorded spontaneous EPSCs (sEPSCs) from cells of the LGN during ON/OFF sublamination. We also examined retinal inputs specifically by stimulating the optic tract in the presence of strontium and recording evoked miniature EPSCs (emEPSCs). The rise times, areas, half-widths, and decay times of sEPSCs and emEPSCs and interevent intervals of sEPSCs recorded at the beginning of ON/OFF sublamination were not different from those recorded after its completion. Typically EPSC areas were small (10-20 fC) but varied greatly both within and between neurons. The frequency of sEPSCs was also quite variable, ranging from 0.2 to 5 Hz. sEPSCs were equivalent to miniature EPSCs recorded in the presence of tetrodotoxin, and both sEPSCs and emEPSCs were CNQX-sensitive. No difference was observed between sEPSCs recorded at room temperature and those recorded at 34 degreesC, and strontium could be substituted for calcium with no effect on sEPSC shape. These data argue for a remarkable stability in the components of at least AMPA-mediated synaptic transmission during a period of major synaptic rearrangement in the LGN.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Brainstem inputs to the ferret medial geniculate nucleus and the effect of early deafferentation on novel retinal projections to the auditory thalamus.

Following specific neonatal brain lesions in rodents and ferrets, retinal axons have been induced to innervate the medial geniculate nucleus (MGN). Previous studies have suggested that reduction of normal retinal targets along with deafferentation of the MGN are two concurrent factors required for the induction of novel retino-MGN projections. We have examined, in ferrets, the relative influence of these two factors on the extent of the novel retinal projection. We first characterized the inputs to the normal MGN, and the most effective combination of neonatal lesions to deafferent this nucleus, by injecting retrograde tracers into the MGN of normal and neonatally operated adult ferrets, respectively. In a second group of experiments, newborn ferrets received different combinations of lesions of normal retinal targets and MGN afferents. The resulting extent of retino-MGN projections was estimated for each case at adulthood, by using intraocular injections of anterograde tracers. We found that the extent of retino-MGN projections correlates well with the extent of MGN deafferentation, but not with extent of removal of normal retinal targets. Indeed, the presence of at least some normal retinal targets seems necessary for the formation of retino-MGN connections. The diameters of retino-MGN axons suggest that more than one type of retinal ganglion cells innervate the MGN under a lesion paradigm that spares the visual cortex and lateral geniculate nucleus. We also found that, after extensive deafferentation of MGN, other axonal systems in addition to retinal axons project ectopically to the MGN. These data are consistent with the idea that ectopic retino-MGN projections develop by sprouting of axon collaterals in response to signals arising from the deafferented nucleus, and that these axons compete with other sets of axons for terminal space in the MGN.

Age Factors↗
PubMed1998

Specification of retinogeniculate X and Y axon arbors in cats: fundamental differences in developmental programs.

Monocular enucleation at E36, followed by intracellular labeling of single, physiologically identified X and Y axons, demonstrates fundamental differences in their termination patterns within the lateral geniculate nucleus (LGN). X axons have arbors that appear normal in their dorsoventral extent, though some are located in inappropriate regions of the LGN. Y axons have arbors that are either abnormally tall, spanning the entire extent of the LGN, or of normal height but located in inappropriate regions of the LGN. These termination patterns resemble patterns seen after monocular enucleation at E44, and reinforce the conclusion that X and Y axons differ fundamentally in the cues that constrain the dorsoventral extents of their arbors.

Animals↗
PubMed1998

Nitric oxide as a signaling molecule in visual system development.

The lateral geniculate nucleus (LGN) of the ferret is characterized by the readily discernible anatomical patterning of afferent terminations from the retina into both eye-specific layers and On/Off sublaminae. The eye-specific layers form during the first post-natal week, and On/Off sublaminae become apparent during the third to fourth post-natal weeks. The post-natal appearance of these patterns thus provides an advantageous model for the study of the mechanisms of activity-dependent development. The second phase of pattern formation, the appearance of On/Off sublaminae, involves the elaboration of appropriately placed axonal terminals and the restriction (or retraction) of inappropriately placed terminals. Previous work has demonstrated that this process is dependent on the activation of NMDA-receptors. Other studies have provided strong evidence that nitric oxide, a diffusible gas which is produced downstream of NMDA-receptor activation, acts as a retrograde messenger molecule to induce changes in pre-synaptic structures. In this article we review the evidence that nitric oxide plays a role in activity-dependent synaptic plasticity in the developing retinogeniculate pathway. The role of nitric oxide in other aspects of visual system development is also discussed.

Animals↗
PubMed1998

The role of the human papilloma virus in esophageal cancer.

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.

Carcinoma, Squamous Cell↗
PubMed1998

Temporal modulation of spatial borders in rat barrel cortex.

We examined the effects of varying vibrissa stimulation frequency on intrinsic signal and neuronal responses in rat barrel cortex. Optical imaging of intrinsic signals demonstrated that the region of cortex activated by deflection of a single vibrissa at 1 Hz is more diffuse and more widespread than the territory activated at 5 or 10 Hz. With the use of two different paradigms, constant time of stimulation and constant number of vibrissa deflections, we showed that the optically imaged spread of activity is more discrete at higher stimulation frequencies. We combined optical imaging with multiple electrode recording and confirmed that the neuronal response to individual vibrissa stimulation at the optically imaged center of activity is greater than the response away from the imaged center. Consistent with the imaging data, these recordings also showed no response to a second vibrissa deflection at 5 Hz at a peripheral recording site, though there was a significant response to a second vibrissa deflection at 1 Hz at the same peripheral site. These findings demonstrate that vibrissa stimulation at higher frequencies leads to more focused physiological responses in cortex. Thus the spread of activation in rat barrel cortex is modulated in a dynamic fashion by the frequency of vibrissa stimulation.

Animals↗
PubMed1997

Optically imaged maps of orientation preference in primary visual cortex of cats and ferrets.

Feature maps in the cerebral cortex constitute orderly representations of response features created within the cortex; an example is the mapping of orientation-selective neurons in visual cortex. We have compared the properties of orientation maps in area 17 of cats and ferrets, obtained by optical imaging of intrinsic signals. Orientation maps in both species contain a quasi-periodic distribution of iso-orientation domains that are organized into a lattice of pinwheels. However, the spatial density of orientation domains and of pinwheels in ferret area 17 is nearly twice that in cat area 17. The ferret map also contains more discontinuities, or fractures, where orientation changes abruptly. The size of orientation domains scales with interdomain spacing, so that the ratio of the two is approximately the same in both species. Consistent with this finding, the orientation tuning width of individual pixels is similar in the two. The magnitude of orientation preference, however, is much lower in ferret compared to cat. The greater incidence of fractures in ferret appears to be due to proportionately greater overlap between domains of different orientations, particularly along fracture lines that link pinwheel centers. We hypothesize that a key determinant of orientation maps, the relationship between orientation domain size and spacing, expresses an anatomical link between sizes of thalamocortical arbors and horizontal intracortical connections in area 17.

Animals↗
PubMed1997

Experimentally induced retinal projections to the ferret auditory thalamus: development of clustered eye-specific patterns in a novel target.

We have examined the relative role of afferents and targets in pattern formation using a novel preparation, in which retinal projections in ferrets are induced to innervate the medial geniculate nucleus (MGN). We find that retinal projections to the MGN are arranged in scattered clusters. Clusters arising from the ipsilateral eye are frequently adjacent to, but spatially segregated from, clusters arising from the contralateral eye. Both clustering and eye-specific segregation in the MGN arise as a refinement of initially diffuse and overlapped projections. The shape, size, and orientation of retinal terminal clusters in the MGN closely match those of relay cell dendrites arrayed within fibrodendritic laminae in the MGN. We conclude that specific aspects of a projection system are regulated by afferents and others by targets. Clustering of retinal projections within the MGN and eye-specific segregation involve progressive remodeling of retinal axon arbors, over a time period that closely parallels pattern formation by retinal afferents within their normal target, the lateral geniculate nucleus (LGN). Thus, afferent-driven mechanisms are implicated in these events. However, the termination zones are aligned within the normal cellular organization of the MGN, which does not differentiate into eye-specific cell layers similar to the LGN. Thus, target-driven mechanisms are implicated in lamina formation and cellular differentiation.

Afferent Pathways↗
PubMed1997

Blockade of afferent impulse activity disrupts on/off sublamination in the ferret lateral geniculate nucleus.

The ferret retinogeniculate projection is organized into on/off sublaminae within each eye-specific layer. The role of afferent activity in the formation of these sublaminae was examined. We report that when the activity of retinal ganglion cells is blocked with tetrodotoxin during postnatal weeks three and four, on/off sublamination is disrupted, supporting a role for afferent activity in the formation of this pattern.

Afferent Pathways↗
PubMed1997

Integration of local inputs in visual cortex.

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.

Animals↗
PubMed1997

Symmetrical multifocal liposarcoma.

Multiple liposarcomas are extremely rare. We report on a patient with liposarcoma of the right lower limb who had undergone surgery and radiotherapy 4 years previously for a liposarcoma in the left lower limb. An outline of the management is discussed and a short review of available literature is given.

Humans↗
PubMed1996

Orientation maps of subjective contours in visual cortex.

Responses to subjective contours in visual cortical areas V1 and V2 in adult cats were investigated by optical imaging of intrinsic signals and single-unit recording. Both V1 and V2 contain maps of the orientation of subjective gratings that have their basis in specific kinds of neuronal responses to subjective orientations. A greater proportion of neurons in V2 than in V1 show a robust response to subjective edges. Through the use of subjective stimuli in which the orientation of the luminance component is invariant, an unmasked V1 response to subjective edges alone can be demonstrated. The data indicate that the processing of subjective contours begins as early as V1 and continues progressively in higher cortical areas.

Animals↗
PubMed1996

A role for nitric oxide in the development of the ferret retinogeniculate projection.

The ferret retinogeniculate projection segregates into eye-specific layers during the first postnatal week and into ON/OFF sublaminae, which receive inputs from either on-center or off-center retinal ganglion cells, during the third and fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye-specific layers appears to depend on action potential activity () but does not require activation of NMDA receptors (). The formation of ON/OFF sublaminae is also activity-dependent and is disrupted by in vivo blockade of NMDA receptors (). To investigate a possible mechanism whereby blockade of postsynaptic NMDA receptors in the lateral geniculate nucleus (LGN) results in changes in the size and position of presynaptic axon arbors, we tested the role of the diffusible messenger nitric oxide (NO) in the development of the retinogeniculate pathway. We found previously that NO synthase (NOS) is transiently expressed in LGN cells during the refinement of retinogeniculate projections (). In this study, treatment with NG-nitro-L-arginine (L-NoArg), an arginine analog that inhibits NOS, during the third and fourth postnatal weeks resulted in an overall pattern of sublamination that was significantly reduced compared with normal and control animals. Single retinogeniculate axon arbors were located in the middle of eye-specific layers rather than toward the inner or outer half as in normal or control animals. The effect of NOS inhibition was not a consequence of the hypertensive effect of L-NoArg. In contrast to the effect of L-NoArg on the formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal week did not disrupt the formation of eye-specific layers. Biochemical assays indicated significant inhibition of NOS during both treatment periods. These data suggest that NO acts together with NMDA receptors in activity-dependent refinement of connections during a specific phase of retinogeniculate development.

Animals↗
PubMed1996

Subthreshold facilitation and suppression in primary visual cortex revealed by intrinsic signal imaging.

Neurons in primary visual cortex (area 17) respond vigorously to oriented stimuli within their receptive fields; however, stimuli presented outside the suprathreshold receptive field can also influence their responses. Here we describe a fundamental feature of the spatial interaction between suprathreshold center and subthreshold surround. By optical imaging of intrinsic signals in area 17 in response to a stimulus border, we show that a given stimulus generates activity primarily in iso-orientation domains, which extend for several millimeters across the cortical surface in a manner consistent with the architecture of long-range horizontal connections in area 17. By mapping the receptive fields of single neurons and imaging responses from the same cortex to stimuli that include or exclude the aggregate suprathreshold receptive field, we show that intrinsic signals strongly reveal the subthreshold surround contribution. Optical imaging and single-unit recording both demonstrate that the relative contrast of center and surround stimuli regulates whether surround interactions are facilitative or suppressive: the same surround stimulus facilitates responses when center contrast is low, but suppresses responses when center contrast is high. Such spatial interactions in area 17 are ideally suited to contribute to phenomena commonly regarded as part of "higher-level" visual processing, such as perceptual "popout" and "filling-in."

Animals↗
PubMed1996

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

BACKGROUND: Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes. METHODS: In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes. RESULTS: Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells. CONCLUSIONS: HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Adult↗
PubMed1996

Anterograde axonal tracing with the subunit B of cholera toxin: a highly sensitive immunohistochemical protocol for revealing fine axonal morphology in adult and neonatal brains.

We report an improved immunohistochemical protocol for revealing anterograde axonal transport of the subunit B of cholera toxin (CTB) which stains axons and terminals in great detail, so that single axons can be followed over long distances and their arbors reconstructed in their entirety. Our modifications enhance the quality of staining mainly by increasing the penetration of the primary antibody in the tissue. The protocol can be modified to allow combination in alternate sections with tetramethylbenzidine (TMB) histochemical staining of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Using the protocol, we tested the performance of CTB as an anterograde tracer under two experimental paradigms which render other anterograde tracers less sensitive or unreliable: (1) labeling the entire retinofugal projection to the brain after injections into the vitreal chamber of the eye, and (2) labeling developing projections in the cortex and thalamus of early postnatal mammals. Qualitative comparisons were made with other tracers (Phaseolus vulgaris leucoagglutinin, dextran rhodamine, biotinylated dextran, free WGA, or WGA-HRP) that were used to label these same projections. From these observations it is clear that CTB, visualized with our protocol, provides more sensitive anterograde labeling of retinofugal projections as well as of axonal connections in the neonatal forebrain.

Animals↗