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T A Woolsey

Publications and source records attributed to T A Woolsey.

At least 55 records · Page 3Linked to original sources
PubMed1987

Axonal trajectories between mouse somatosensory thalamus and cortex.

An in vitro brain slice preparation has been used to label fibers connecting the somatosensory thalamus and cortex of the mouse. In 400-800-micron brain slices, the pathway between the ventrobasal complex and somatosensory cortex was labeled under direct vision with horseradish peroxidase crystals (HRP), HRP-Nonidet P-40 (NP40) detergent chips, or a solution of HRP/dimethylsulfoxide. Thalamocortical and corticofugal fibers are organized into a plexiform system of bundles that appears to be fairly constant from animal to animal. Bundles of fibers projecting from the ventrobasal complex course between regularly spaced groups of thalamic neurons. Thalamocortical axons do not invariably leave the thalamus via the fiber bundle closest to the perikarya. Thus, nearest-neighbor relationships are abolished before these axons have even left the thalamus. The axon bundles traverse the thalamic reticular nucleus lateral to the complex. The axons then rotate about one another, analogous to the coiling of strands in rope about a central axis. This accounts for the well known 180 degrees rotation in the mediolateral direction between thalamic and cortical maps. Laterally, fiber bundles converge and diverge within the internal capsule so that nearest-neighbor relationships are lost. Individual thalamocortical axons do not bifurcate proximal to the subcortical white matter. After single bundles of fibers reach a point just below the subcortical white matter, their individual fibers diverge widely. Within the subcortical white matter most afferent fibers make a small dorsally concave loop prior to taking one of two possible courses: some of the fibers ascend directly into the overlying cortex usually angled towards the dorsal surface of the brain; other fibers run in the subcortical white matter for variable distances prior to ascending into cortex. Within somatosensory cortex, smooth axons branch near their terminals in layers IV and VI. Axonal terminal and branching patterns of these axons within somatosensory cortex are similar to those found in in vivo preparations. Most axons are smooth, but other axons are beaded. Some beaded axons project to layer I. Corticofugal fibers are labeled. Fibers leaving somatosensory cortex have an angle of descent opposite to the angle of ascent for afferent fibers, and are often fasciculated in the cortex and subcortical white matter. Within the subcortical white matter efferent fibers often loop in a direction opposite to that of afferent fibers. Corticofugal fibers occasionally give off a collateral corticostriatal branch within the internal capsule.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1987

Quantitative histochemical and microchemical changes in the adult mouse central nervous system after section of the infraorbital and optic nerves.

The sensory projections from the whiskers of mice and other rodents synapse somatotopically in 3 subnuclei in the brainstem trigeminal complex, in the ventrobasal complex of the thalamus and in the somatosensory cortex. Deafferentation of the whiskers in adult animals results in qualitative and quantitative changes in activities of the metabolic enzymes in the somatosensory cortex (e.g. J. Neuro-sci., 1 (1981) 929-935). We determined the time course and extent of changes in the subcortical trigeminal centers of adult mice after deafferentation. The right infraorbital nerve was sectioned in mice under surgical anesthesia; the animals survived for periods up to 26 weeks. The optic nerve was also cut to evaluate the effects of central tract section. Some brains were prepared histochemically for the mitochondrial enzymes cytochrome oxidase (CO) and succinic dehydrogenase (SDH), and some were prepared for microchemical analysis of the enzymes citrate synthase (CS), malate dehydrogenase (MDH) and phosphorylase. All deafferented and intact nuclei were examined in each animal quantitatively. The oxidative enzymes (CO, SDH, CS and MDH) that were analyzed by histochemical and microchemical approaches showed a decrease in activities as early as 3 weeks postdeafferentation, a trend that continued up to 12 weeks in all the subcortical trigeminal stations and lateral geniculate nucleus (LGN) when compared with the intact side. By 25 weeks postlesion, the levels were comparable to the intact side except that in the LGN, the levels remained depressed. The phosphorylase levels increased at around 3 weeks postoperation and remained elevated 25 weeks postlesion. Each case provided results on the effects of deafferentation at a given time point throughout the trigeminal pathway. Direct quantitative correlation of histochemical and microchemical approaches for glycolytic enzymes is consistent with a coordinate regulation of these molecules. The changes in enzyme levels in all nuclei occur simultaneously and to a similar degree. This strongly suggests that neuronal activity plays an important role in regulating metabolic machinery throughout this pathway in adults.

Animals↗
PubMed1987

Templates for locating the whisker area in fresh flattened mouse and rat cortex.

A way was devised to locate the projection fields (barrels) of the whiskers in fresh neocortex of rats and mice. The cortex was quickly removed and flattened prior to fixation and staining for cytochrome oxidase. The barrels were mapped in relation to the flattened cortex by superimposing specimen and vascular outlines. The topographic location of the barrel field is consistent in rats and in mice. Simple templates were made by xerography on transparency film. Templates were used to accurately excise the barrel cortex of SmI from cortex or to place in vitro injections of HRP. The approach could be generalized to locate other cortical areas from lissencephalic brains.

Animals↗
PubMed1986

In vitro labeling of axonal projections in the mammalian central nervous system.

Horseradish peroxidase crystals or HRP-NP40 detergent chips were directly applied to brain slices from mice to label primary afferent fibers and their terminal arbors in the brainstem trigeminal complex, and neurons of the ventrobasal complex of the thalamus, their axons in the internal capsule, and their terminals in the primary somatosensory cortex. Anterograde and retrograde labeling of fibers, as well as retrograde labeling of somata, were observed. In vitro labeling of selected non-trigeminal structures and fiber pathways was also demonstrated. Experimental variables have been dealt with in some detail, as have specific advantages and disadvantages of the technique. This in vitro HRP labeling method for neuronal fiber systems is a useful adjunct to currently employed in vivo labeling techniques in the mammalian central nervous system.

Animals↗
PubMed1986

Effect of a uniform partial denervation of the periphery on the peripheral and central vibrissal system in guinea pigs.

In some rodents, somatotopically organized architectonic patterns corresponding precisely to the arrangement of the vibrissae on the face are found in each of the central stations of the trigeminal (V) pathway. Two lines of evidence indicate that these architectonic patterns reflect the level of peripheral innervation. First, in normal mice, the sizes of the individual units within the cortical representation are proportional to the number of fibers supplying the corresponding vibrissal follicles. Second, complete surgical denervation of groups of vibrissae can severely attenuate the sizes of and alter the patterns of their central representations. However, previous studies in this system do not distinguish the effects of the absolute and the relative levels of peripheral innervation on central representations. To address this question, we have studied guinea pigs in which all vibrissae are partially deafferentated before birth by fetal exposure to antibodies against NGF. This approach reduces the absolute level of peripheral innervation in a graded way, and does so uniformly, without changing the pattern of vibrissal innervation. In the most severely affected animals, only 18% of the normal number of V ganglion neurons survive. The effect of this loss on the V system was assessed by comparing the peripheral and central components of the vibrissal system in normal and NGF-deprived animals. Peripheral fibers from the V ganglion neurons, including those to the vibrissae, are less reduced in number (50%) than expected. The number of peripheral fiber fascicles is also decreased. In contrast, neither the patterns nor the areas of the central representations in medulla and cortex differ from those of normal animals. We conclude that 18% of the normal number of V ganglion cells is sufficient to establish normal central architectonic patterns and the size of the central vibrissal representations is independent of the absolute magnitude of peripheral innervation. These observations are of relevance to understanding the role of NGF on the morphogenesis of central somatosensory pathways, the effects of "mismatches" between peripheral innervation, and the development of projections to central targets in the mammalian brain, and provide new data for understanding competitive interactions in the developing central and peripheral trigeminal system.

Animals↗
PubMed1985

Functional organization in cortical barrels of normal and vibrissae-damaged mice: a (3H) 2-deoxyglucose study.

The large mystacial vibrissae on the faces of rodents have punctate representations in all stations in the central trigeminal pathway, including layer IV of the somatosensory cortex (SmI). The cortical whisker correlates, multicellular units termed barrels, are not present at birth, and damage to the vibrissae during the first postnatal week results in altered adult cytoarchitectonics. The anatomical effects of vibrissae damage in the cortex have been well documented; here, we investigated the functional organization of altered SmI barrels with a high-resolution 2-deoxyglucose (2-DG) technique (Durham et al., '81, J. Neurosci. 1:519). The middle row of vibrissae was cauterized in 1-, 2-, 3-, 4-, or 5-day-old mice, and the animals were allowed to survive to sexual maturity. Various combinations of vibrissae were clipped acutely 24 hours prior to injection of 2-4 mCi of (3H)2-DG. Mice actively explored an empty cage for 60 minutes, stimulating the remaining vibrissae. The mice then were perfused and their brains prepared for paraffin histology and emulsion autoradiography. In tangential sections through layer IV, patterns of neuropil and cell body labeling were analyzed with respect to barrel cytoarchitecture in normal and vibrissae-damaged mice. In both control and experimental animals, patterns of neuropil and cell somata label corresponded exactly to barrel boundaries, whether normal or altered by vibrissae damage. Only those barrels for which vibrissae were intact had high levels of label, with anterior barrels more heavily labeled. Many neurons in the septa between these barrels and the adjacent barrels were labeled also. We found slightly higher neuropil label in the cortical zone corresponding to the damaged zone on the face in animals lesioned at any time. These data indicate that physiological somatotopy in vibrissae-damaged animals matches the anatomical cytoarchitecture.

Afferent Pathways↗
PubMed1984

Morphology of Golgi-Cox-impregnated barrel neurons in rat SmI cortex.

Golgi-Cox-impregnated neurons in the barrel cortex of the rat were studied qualitatively and quantitatively. Adult rat brains were sectioned perpendicular to or parallel to the cortical representation of the large facial vibrissae at 125 micron. Cortical laminar and barrel boundaries were identified from the Nissl counterstain. Over 200 well-impregnated neurons in cortical layers I-IV were selected for classification and further detailed study. Three broad classes of neurons were recognized: (1) pyramidal cells with conical somata, a stout apical dendrite, and spines; (2) class I nonpyramidal cells having small spherical somata and spiny dendrites; and (3) class II nonpyramidal cells having larger ellipsoid somata and smooth or beaded dendrites. The class I cells were further subdivided into "star pyramids" (cells with an apical dendrite) and spiny stellate cells (cells in which all dendrites were of similar length). The class II cells also were subdivided into multiform cells (with multiple dendrites radiating from the soma) and bipolar cells (with two principal dendritic trunks arising from the superficial and deep aspects of the soma). The position of these various cell types in the superficial cortical laminae was mapped in sections normal to the pia. Numerous examples of the class I and class II neurons were drawn with respect to the barrels in layer IV and the extent of their processes noted. Finally, approximately 250 barrel-related class I and II neurons were studied quantitatively using a computer-microscope and digitizing tablet. The density of the Golgi-impregnated neurons corresponds to the pattern of cell density seen with the Nissl counterstain. The various cell types are not uniformly distributed as a function of cortical depth. Cells with apical dendrites were found principally in the supragranular layers and star pyramids in the superficial one-half of layer IV. Spiny stellate cells are concentrated in layer IV and the smooth cells are present in greatest number in deep layer III and deeper layer IV. On the basis of these distributions we suggest that layer IV be subdivided into two sublaminae. The class I and class II neurons can be distinguished according to quantitative criteria which apply in either plane of section used. Class I neurons have smaller projected somal areas, more proximal dendritic branching, and shorter dendrites when class I and II neurons are measured in three dimensions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Cytoarchitectonic correlates of the vibrissae in the medullary trigeminal complex of the mouse.

Cytoarchitectonic patterns in the medullary trigeminal complex of the mouse corresponding to mystacial vibrissae are described. These patterns are found within trigeminal sub-nuclei principalis, interpolaris and caudalis. The patterns are due to differential cell packing and are homeomorphic to the arrangement of the mystacial vibrissae on the face. The cytoarchitecture is similar, but complementary, to patterns of trigeminal afferents previously described using histochemical staining methods. Neonatal cautery of groups of vibrissae produces appropriate, specific and localized cytoarchitectural changes within all 3 trigeminal sub-nuclei.

Animals↗
PubMed1984

Effects of neonatal whisker lesions on mouse central trigeminal pathways.

The mystacial vibrissae or whiskers on the face have a large representation in the rodent central nervous system. In rats and mice the projections arising from each vibrissa can be demonstrated histologically in five separate parts of the central trigeminal pathway. At every location, the pattern of the projections is isomorphic to the pattern of the facial vibrissae. For example, in the somatosensory cortex (SmI), multicellular cytoarchitectonic units in layer IV--termed barrels--correspond anatomically and functionally to the contralateral whiskers. The cortical barrels are absent at birth and their cytoarchitectonic pattern can be altered by neonatal whisker lesions. The effect is graded such that whisker damage on or after postnatal day (PND) 6 does not produce changes in the anatomical somatotopy. We undertook the present study to determine whether similar "critical periods" for susceptibility to vibrissa damage exist in the subcortical trigeminal stations of mice. In particular, we wished to find out whether subcortical projections are susceptible to whisker damage in a sequence which parallels other described developmental sequences, as has been concluded from previous work on the mouse (Woolsey et al., '79), or whether the "critical periods" are related to other aspects of development as has been concluded from work on the rat (Belford and Killackey, '80). Neonatal Swiss Webster mice sustained lesions of a single row of whiskers on PND 1, 2, 3, 4, or 5. The animals survived to adulthood. Their brains were sectioned and stained for the mitochondrial enzyme, succinic dehydrogenase (SDH), which demonstrates whisker somatotopy in all central nervous system (CNS)stations. The whisker representations at each level of the pathway, often in the same individual, were reconstructed from serial sections to assess qualitative and quantitative changes in somatotopy. Histological sections through the faces of the experimental animals were used to determine the extent of whisker damage and to show that few nerve fibers innervate the damaged zone on the face. In the brainstem representations, the zones corresponding to the damaged whiskers are shrunken and pale, regardless of the animal's age at vibrissa damage; this probably reflects the degeneration of the primary afferents. In the thalamus and the cortex, whisker damage at later postnatal times has progressively less effect on the anatomical projections patterns. Based on the changes in the projection patterns related to the damaged vibrissae and the changes in the projection patterns related to the remaining, intact vibrissae,(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Functional organization of mouse and rat SmI barrel cortex following vibrissal damage on different postnatal days.

This study was undertaken to determine the functional properties of neurons in the anatomically altered somatosensory cortex after neonatal whisker damage. In mice and rats neonatal lesions of the facial vibrissae change the anatomical organization of barrels in the contralateral SmI cortex. These changes depend on the pattern and severity of the peripheral damage and the developmental age of the animals. To understand some of the functional correlates of these anatomical changes, the middle row of vibrissae (row C) was damaged in mice on postnatal days 1, 3, and 5 and in rats on postnatal days 1 and 5. The receptive field properties of single cortical units were studied after the animals matured. In 24 mice and 15 rats a total of 1,370 units were characterized in microelectrode penetrations which passed through the somatosensory cortex either tangential or perpendicular to the pia. Units were localized anatomically with respect to both barrel and laminar boundaries, and the extent of the peripheral damage was assessed histologically. The data revealed an orderly representation of the sensory periphery that coincided with the altered cytoarchitectonic organization of the SmI cortex. Specifically: (1) Units in the enlarged row B or row D barrels responded primarily to row B or row D whiskers. (2) In layer IV, units in the altered row C cortex either could not be reliably driven from the periphery, were activated by stimulation of scar tissue in the damaged facial row C, or were driven by adjacent, intact row B or row D whiskers. (3) Units in supra- and infragranular layers either had no row C representation or incorporated scar tissue in their receptive fields in a topographically correct fashion. Responses of units to stimulation of scar tissue were qualitatively similar to those elicited from intact vibrissae, which also activated them. (4) In SmII, units that responded to whiskers had receptive fields whose organization matched the representation of the periphery observed in SmI. (5) There was no mapping of nonmystacial pad structures in the barrel cortex, and there were no units with abnormal multiwhisker interactions when laminar boundaries were taken into account. These data indicate that neonatal damage to the whiskers alters both the anatomical arrangement of the barrels and the physiologically determined somatotopic representation of the sensory periphery in a parallel and predictable fashion.

Age Factors↗
PubMed1983

Computer-assisted analyses of barrel neuron axons and their putative synaptic contacts.

The "barrels" in layer IV of rodent SmI neocortex receive inputs from individual whiskers on the contralateral face. Previous analyses of neuronal morphology in mouse and rat barrel cortex, as revealed by Golgi impregnations, have focused on the dendritic patterns of the stellate cells. The cells can be classified into two groups: Class I cells with spiny dendrites and Class II cells with smooth, beaded dendrites. These classes can be subdivided further according to somal position and spatial distribution of dendrites with respect to barrel cytoarchitectonic boundaries. In the present study the axons of these cells were examined and the locations of close appositions to dendrites of other impregnated neurons were mapped. All data are taken from Golgi-Cox preparations, cut parallel to layer IV at 140 microns, counterstained with Nissl to reveal the barrels, and measured with a computer-microscope. Axons which had extensive branching within the section (present on 10% of all impregnated cells) were chosen for measurement. The analysis of the axons revealed: (1) Class I axons are thin and directed to the white matter with recurrent collaterals in the barrels, while Class II axons are thick, frequency beaded, and directed toward the pia before cascading down into the barrels; (2) in layer IV, the axons of both cell classes tend to be as restricted to a barrel as the dendrites of the same cell are (i.e., most axons are confined to one barrel); (3) within layer IV, the Class II cell axons have a total length about three times that of Class I cell axons, and about four times as many branch points. The analysis of the appositions of these axons to impregnated dendrites of other cells revealed: (1) A majority of "contacts" tended to be made by terminal branches of the axonal trees. (2) For the Class I neurons, a greater number of appositions occur near the distal ends of complete dendritic segments. As measured from the "contacted" cell soma, appositions are more or less uniformly distributed along dendritic trees. (3) No striking patterns are found, such as an obvious propensity for axons of one cell type to prefer or avoid another cell type. These results show that the axons of barrel cells of each class are as consistent and distinctive as their dendritic trees. Specifically, the cells in each class can be distinguished by their axonal patterns on purely numerical bases.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Binding of isolated 3T3 surface membranes to growing 3T3 cells and their effect on cell growth.

We have quantitated by autoradiography the binding of [125I]labeled 3T3 plasma membrane fragments to 3T3 cells growing on the surface of plastic dishes; ie, the same conditions in which these membranes specifically arrest the growth of 3T3 cells early in the G1 phase of the cell cycle. We have been able to demonstrate that binding of membranes to cells is coincidental with the expression of the growth inhibitory activity of protein(s) present in the membrane fragments. Treatments that reduce binding (heat denaturation of the membranes or culture in the presence of high serum) also reduce growth inhibitory activity. [125I]labeled membranes bound to cells are located primarily on the cell surface (as determined by electron microscope autoradiography) and are exchangeable with unlabeled membranes. We conclude that binding of membranes to cells is necessary but may not be sufficient for the expression of the growth inhibitory activity of these membranes. This approach provides information not only on the average level of binding of membranes to cells, but also provides a quantitative assessment of the variation of the level of membrane to cell binding between different cells in the population.

Animals↗
PubMed1982

"Increased" sensory stimulation leads to changes in energy-related enzymes in the brain.

The facial whiskers of mice project through several synapses to anatomically distinct structures called barrels in the contralateral cerebral cortex. With appropriate illumination, individual barrels can be recognized and dissected from unfixed, freeze-dried tissue sections taken parallel to the plane of layer IV. The tissue then can be analyzed using quantitative microhistochemical techniques to determine the level of various substances of biological importance (W.D. Dietrich, D. Durham, O. H. Lowry, and T. A. Woolsey (1981) J. Neurosci. 1: 929-935). The present paper describes results obtained in this way from adult mice subjected to a chronic "sensory deprivation" by repeatedly clipping all of the whisker hairs on one side of the face and during the recovery from this deprivation in which the whisker hairs were allowed to grow back. Sensory deprivation for 60 days leads to significant changes in the levels of the three energy-related enzymes studied--citrate synthase, malate dehydrogenase, and glycogen phosphorylase. surprisingly, during clipping, the enzyme levels in the barrels of the contralateral cortex are essentially normal, whereas enzyme levels in the barrels of the ipsilateral cortex are increased significantly. Specifically, activities expressed as a percentage of levels in normal animals were: citrate synthase, 135%; malate dehydrogenase, 130%; and glycogen phosphorylase, 170%. Forty-five days after the deprivation is reversed, the levels return to normal. These significant changes occurred in adult mice several synapses away from the sensory periphery. The data are in contrast to our earlier results in which damage to the primary afferents reduced the levels of the enzymes citrate synthase and malate dehydrogenase contralateral to the manipulation. A possible explanation for the enzymatic changes observed in the cortex ipsilateral to the clipped whiskers is an increased utilization of the intact sensory periphery by the animals; this has some behavioral support.

Animals↗
PubMed1981

Dendritic plasticity in mouse barrel cortex following postnatal vibrissa follicle damage.

Neonatal damage to a row of mystacial vibrissae in the mouse causes cytoarchitectonic alterations in the contralateral SmI barrel Cortex. The region for the appropriate row of barrels develops as a smaller homogeneous zone while barrels in adjacent rows are expanded. To investigate the effects of this phenomenon on the morphology of individual neurons, adult mice in which Row-C vibrissae (the middle row) had been cauterized on days 1--5 following birth were processes by the Golgi-Cox method. All neurons in layer IV of the Row-C zones, of the Row-C barrels of a control hemisphere, and some neurons in the adjacent enlarged Row-B barrels were measured with a computer-assisted microscope. Their location with respect to cytoarchitectonic boundaries was determined from a Nissl counterstain. Data from 239 cells are presented. For each cell, measures of dendritic length and branching were obtained. The orientation of the dendritic trees with respect to the barrel sides was also measured. The measures of dendritic lengths and branching did not show any differences between control and experimental animals or between animals damaged on different days. Measures of orientation did show changes related to the age at the time of damage. In animals damaged on postnatal day (PND)-3 or earlier, many cells in the Row-C zone were observed with dendrites orienting toward the adjacent Rows-B or -D. "Putative" Row-C cells in the expanded parts of Rows-B and -D were strongly oriented toward barrels in those rows. These results suggest that dendritic length and branching may be determined intrinsically but that the orientation of the dendritic trees appears to be strongly influenced by the pattern of extrinsic afferent inputs from the thalamus. In the case of the whisker-damaged animals, the orientation of the Row-C neuron dendritic trees toward the "functional" thalamocortical inputs in Rows-B and -D contributes strongly to the resultant cytoarchitectonic changes. The implications of these results for normal developmental processes and their relationship to functional studies of the cortex are considered.

Aging↗
PubMed1981

Cellular localization of 2-[3H]deoxy-D-glucose from paraffin-embedded brains.

Results of experiments in which regional neuronal activity is revealed by a 2-[3H]deoxy-D-glucose (3H-2-DG)-paraffin section-emulsion autoradiography method are described. The trigeminal pathway of freely behaving mice was activated differentially by selective patterns of whisker removal. One hour after injection of concentrated 3H-2-DG, the animals were perfused systemically with a periodate/lysine/paraformaldehyde mixture (McLean, I. W., and P. K. Nakane (1974) J. Histochem. Cytochem. 22: 1077-1083), the brains were embedded in paraffin, and serial sections were taken and coated with emulsion for autoradiography. Diffusion of the isotope out of the tissue was assessed visually and by liquid scintillation counting. While substantial loss of 3H isotope into the embedding fluids (about 95%) was found, the scintillation counts and the autoradiograms showed good fixation of the isotope in situ, no evidence of isotope movement into the emulsion, and no gradients of diffusion in the sectioned material. Patterns of regional labeling were similar to those reported from brains prepared by conventional 2-[14C]deoxy-D-glucose (14C-2-DG) autoradiography; for instance, auditory and vestibular pathways in the brainstem were heavily and specifically labeled. Trigeminal structures associated with the intact (stimulated) whiskers were labeled relatively heavily, indicating that label uptake is specific with respect to neuronal activity. In the cortex, the patterns of label corresponded directly and precisely to those barrels known to receive inputs from the intact whiskers. Distribution of silver grains in the cortex and in the brainstem was correlated directly with neuronal profiles, including processes, some of which were identified by means of a Nissl counterstain. Clearly, this approach offers considerable technical advantages, in particular, the ease with which the histological material is prepared. The resolution of the autoradiograms and the quality of the histology are excellent.

Animals↗