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P J Hand

Publications and source records attributed to P J Hand.

At least 19 recordsLinked to original sources

Representation of a single vibrissa in the rat neostriatum: peaks of energy metabolism reveal a distributed functional module.

In unanaesthetized rats, mechanical stimulation of a single vibrissa increased glucose utilization in one cortical column of the somatosensory area and in several spots in the dorsolateral neostriatum, predominantly on the side contralateral to the stimulation. Two or three peaks of glucose utilization unique to the stimulated animals were seen in cross sections throughout a 1.8 mm anteroposterior extent in the dorsolateral striatum. These observations suggest that one cortical column is functionally related to several neostriatal regions. The distributed modularity may be an important characteristic of the basal ganglia system.

Animals

Three-dimensional reconstruction of activated columns from 2-[14C]deoxy-D-glucose data.

Three-dimensional (3-D) reconstruction of autoradiograms can provide new insights into the functional relationship of neural regions. To reach full potential, however, 3-D reconstruction must be both accurate and efficient. In this paper, we present a novel image matching algorithm that simultaneously aligns a set of serial sections and uses the method to reconstruct whisker barrels from the rat cerebral cortex. We initially compared several alignment techniques and found that our Multi-Set Registration (MSR) algorithm produced superior accuracy. This algorithm is based on a least-squares minimization technique and is able to simultaneously register a set of serial sections with subpixel precision (30-micron accuracy). We applied our new technique to the 3-D reconstruction of a series of autoradiograms. Our objective was to visualize and measure the 3-D metabolic (functional) shape of normal (control) and developmentally altered (plastic) C3 vibrissa columns in the first somatosensory area of the rat cerebral cortex. The plastic C3 metabolic column showed a nearly 450% increase in volume when compared to the control column. In addition, the lesion-altered C3 column-in contrast to the normal C3 column-displayed no central zone of high activity, and patches of higher metabolic activity were scattered throughout the columnar profile. This metabolic activity was not confined to the cylindrical column, but extended tangentially as radiating fingerlike projections toward neighboring barrels.

Algorithms

Prevalence of disease in nonviremic cats previously exposed to feline leukemia virus.

Feline leukemia virus status and antibody titer to feline oncornavirus-associated cell membrane antigen (FOCMA) were determined on plasma from 183 outpatient cats and 61 cats from 2 closed, FeLV-positive, multiple-cat households. Cats with FOCMA antibody titer had a significantly (P less than 0.02) higher prevalence of history of disease than did cats without FOCMA antibody. Diseases included upper respiratory tract infections, abscesses, ear infections, lower urinary tract infections, gastrointestinal disease, pneumonia, uterine infection, lymphadenopathy, fever of unknown origin, and bacterial infections. The FOCMA antibody titer was determined by use of an indirect fluorescent antibody test; titer greater than or equal to 1:16 was considered to be positive results. Lower mean FOCMA antibody titer was observed in young cats with history of disease (P less than 0.05) than in young cats without history of disease or in older cats with or without history of disease. Prevalence of FOCMA antibody titer was identical (38%) in young and adult cats, indicating cats likely were exposed to FeLV as kittens because a higher prevalence of FOCMA antibody titer in older cats would otherwise be expected.

Animals

Beta 2-adrenergic receptors are colocalized and coregulated with "whisker barrels" in rat somatosensory cortex.

Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-Adrenergic receptors, but not beta 1-adrenergic receptors colocalize with "whisker barrels" in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array.

Afferent Pathways

The role of norepinephrine in adult rat somatosensory (SmI) cortical metabolism and plasticity.

Stimulation of rat facial vibrissae increases glucose utilization in the corresponding barrels (lamina IV) and associated columns in laminae I-VIa of the contralateral first somatosensory (SmI) cortex as assessed autoradiographically by the uptake of [14C]2-deoxy-glucose (2-DG). Chronic deafferentation (2 months) by bilateral vibrissectomy with sparing of the C3 vibrissa (SC3) in adult Sprague-Dawley rats produced no change in the rate of LCGU but led to an increased areal extent of the metabolic representation of the SC3 barrel (39%, P less than 0.001) and column (31%, P less than 0.003) as compared to rats with fully intact vibrissae. In other rats with intact facial vibrissae, 6-hydroxydopamine lesions of the locus coeruleus (LC) depleted ipsilateral cortical norepinephrine (NE) by more than 90% and, 2 months later, led to an 11% and 21% increase in C3 barrel and column metabolic representations, respectively, as compared to the contralateral SmI cortex with intact NE levels (P less than 0.05). When bilateral vibrissectomy was combined with a unilateral LC lesion, the SC3 barrel and column metabolic representation on the LC-intact side enlarged as expected but no enlargement occurred on the NE-depleted side (20% difference; P less than 0.05). Therefore, the effect of NE on the SmI cortex depends on the status of its afferent input. NE inhibits the spread of metabolic activity beyond the activated barrel and column in the intact cortex, but independently modulates plastic enlargement in the partially deafferented SmI cortex.

Afferent Pathways

Single vibrissal cortical column in SI cortex of rat and its alterations in neonatal and adult vibrissa-deafferented animals: a quantitative 2DG study.

1. A quantitative 2-[14C]deoxy-D-glucose (2DG) autoradiographic study was undertaken to determine the functional (metabolic) organization of an individual column in the first somatosensory cortex (SI) of the awake restrained rat. Manual or mechanically controlled brush stroking of a single vibrissa (typically C3) was used in order to evoke neural activity and increase glucose utilization in a single cortical barrel in lamina IV and in adjacent supra- and infragranular layers in register with the single cortical barrel labeling in lamina IV. 2. The single activated vibrissal column was found to extend from layer I to the superficial half of layer VI of the contralateral SI cortex and was fusiform in shape, being of largest diameter (650-micron) in layer IV and smallest diameter (200 micron) in layer VI. 3. This single metabolic column was not uniform in its density of labeling. The greatest local cerebral metabolic rate of glucose (LCMRG) was found in layer IV (170 mumol.100 g-1.min-1), layers II-III, and V had, on the average, similar LCMRG values (115 mumol.100 g-1.min-1), which decreased with distance from layer IV. 4. The functional (metabolic) columnar activity center situated in layer IV corresponded in size to the appropriate anatomical barrel as determined from thionin-stained sections. Increased metabolic activity was not strictly confined to the candle-pin-shaped column but extended tangentially as radiating fingerlike projections toward the neighboring barrels. 5. In cortical layers other than IV, the metabolic column was less prominently labeled, and the metabolic activity also branched in the tangential plane. The labeling pattern profile in upper layers was characterized by numerous lateral spreading fingerlike projections of increased glucose metabolism. 6. Neonatal follicle lesions sparing only C3 vibrissa caused a great increase (125%) in cortical territory driven by the spared whisker with a concomitant loss of columnar shape and decrease in intensity of metabolic activity in response to its stimulation. 7. Similar lesions in adult rats produced a significant increase (40%) in dimensions of the spared C3 cortical column, which was, however, smaller than that produced after neonatal lesions. The metabolic activation of layer Vb in the spared C3 column was increased (17%) compared with that of the control column.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways

Effects of dexamethasone on electroacupuncture analgesia and central nervous system metabolism.

Many reports have indicated that electro-acupuncture analgesia (EAA) was mediated by endorphins. Among them is B-endorphin which can be released from the anterior lobe of the pituitary. To examine the role of B-endorphin in EAA and observe CNS metabolic (functional) and behavioral effects of dexamethasone the present study employed the (14C) 2-deoxyglycose (2DG) method. Seventeen adult male Sprague-Dawley rats in five groups received the following different types of somesthetic stimulation to examine the local cerebral glucose utilization (LCGU) and tail-flick response latency: control group (N = 3), pain group (N = 4), EA group (N = 3), pain + EA group (N = 3; from another ongoing study) and dexamethasone group (N = 4). Dexamethasone reduced tail-flick response latency in response to electroacupuncture, and produced metabolic (functional) changes in a number of CNS structures implicated in electroacupuncture produced analgesia effects (some changes were statistically significant, many others were not). Specific brain structures exhibiting statistically significant changes (p less than 0.05) in LCGU when compared to the pain + EA group are: the parafascicular and habennlar nuclei of the thalamus and the posterior cingulate gyrus. In comparison of dexamethasone group with the other four experimental groups of rats, the following trend in LCGU changes was observed: pain + EA group greater than pain group = EA group = dexamethasone group greater than control group. In addition, dexamethasone had a sedative effect. The results suggest that dexamethasone is reducing EAA and having suppressive effects on CNS metabolism and behavior.

Acupuncture Therapy

Locus coeruleus input affects glucose metabolism in activated rat barrel cortex.

Significant depletion (greater than 50%) of neocortical norepinephrine (NE), 2 weeks after unilateral 6-hydroxydopamine lesions of the locus coeruleus, led to a small (8%), ipsilateral decrease in total C3 vibrissa column 14C-2-deoxyglucose uptake, but a larger (24-32%) increase in the areal extent of this uptake into the metabolic representation of both the C3 column and barrel of the rat somatosensory (SmI) cortex during stimulation of the contralateral C3 facial vibrissae. This suggests a predominantly inhibitory role for NE in modulating SmI oxidative metabolism during physiologic stimulation.

Animals

The Taub case.

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Animal Husbandry

Autoradiographic deoxyglucose study of visually activated extrastriate cortex in the primate: three-dimensional reconstruction.

Activation of the visual system with a moving black and white geometric pattern resulted in dense patches or columns of 2-deoxyglucose label in primate extrastriate visual cortex. The three-dimensional reconstruction of these metabolic columns showed that they were arranged in irregularly shaped slabs which extended in an essentially rostrocaudal plane. The slabs tended to merge with one another and to subdivide throughout their course in the extrastriate visual cortex.

Animals

Patterns of metabolic activity in cytoarchitectural area SII and surrounding cortical fields of the monkey.

The pattern of [14C]2-deoxyglucose (2-DG) labeling evoked by tactile stimuli was determined in cerebral cortical cytoarchitectural area SII and the fields that surround it (including area 7b, the retroinsular field (Ri), and the granular insular region (Ig) for a series of nine monkeys (macaca fascicularis). In all animals and for all tactile stimuli, the cortical labeling most frequently occurred in the form of patchlike aggregates of metabolically active neurons. Individual patches typically included laminae II-V, were most densely labeled in the central layers, and possessed limited tangential width. Analysis of the relations between patches of label in adjacent sections revealed that the metabolically active neurons form three-dimensional aggregates (termed modules or strips), which can extend for several millimeters. It is hypothesized that these metabolic modules may correspond to information-processing units within the cerebral cortex. Two-dimensional reconstructions of the 2-DG label in the hemispheres ipsilateral and contralateral to the somatic stimuli reveal that the strips of high metabolic activity are interspersed with regions of substantially less activity. In all cortical regions examined in this study, the strips were oriented roughly from anterior to posterior. Systematic changes in the place of the somatic stimulus led to systematic changes in the cortical location of the strips of metabolic label. Conversely, animals subjected to nearly identical tactile stimuli produced very similar patterns of metabolic activity. Comparison of the distribution of metabolic activity in area SII of the hemispheres ipsilateral and contralateral to the stimulus demonstrated that although the amount of labeling in SII ipsilateral to the stimulus was typically less than that present in SII of the contralateral hemisphere, it was both substantial and topographically highly organized. The labeling in the cytoarchitectural zones surrounding SII (i.e., 7b, Ri, and Ig), although clearly stimulus related, occupied extensively overlapping regions in all experiments even though the body regions stimulated were in widely different locations. As a result, a relative lack of topographical organization within these cortical fields is indicated.

Animals

First somatosensory cortical columns and associated neuronal clusters of nucleus ventralis posterolateralis of the cat: an anatomical demonstration.

Microlesions (30--275 microns in diameter) were placed in VPLm of the cat and the terminal axonal degeneration in SI cortex was stained using the Fink-Heimer I technique. Following each of these microlesions, small, localized patches or subcolumns of degeneration, relatively light in density, were observed within laminae IIIb and IV of SI when viewed in the coronal plane. In addition, a few degenerating fibers ascended to lamina I. These multiple subcolumns had distinct radial boundaries and were narrow in the mediolateral plane (80--120 microns in width) but elongated rostro-caudally (2500--3000 microns in length). Localized patches of degeneration were separated at their widest points by a distance of 500 microns medio--laterally, but at various rostro--caudal levels of SI were observed to merge into larger columns of degeneration (250--400 microns) and then separate again into smaller multiple patches (i.e., a "zebra-like" pattern). Small injections of HRP into the forelimb region of area 3b or rostral area 1--2 of SI resulted in the labeling of small, discrete clusters of neurons in the ventral regions of VPLm. The clusters examined ranged in size from 140--350 microns in medio--lateral diameter and were elongated rostro--caudally (up to 500 microns in extent); virtually all cells within a cluster appeared labeled, but not equally so. A pattern of HRP labeling different from that observed following area 3b and rostral area 1--2 injections was observed following injections into more caudal regions of area 1--2 and into SII cortex. The labeling that resulted from these injections was not in the form of neuronal clusters but instead labeled cells tended to be scattered in more dorsal regions of VPLm. This scattering did not appear to be random since the labeled neurons were grouped within the same general area of VPLm. Labeling was distributed throughout a number of cell clusters, comprising only a small proportion of cells within each cluster. The pattern of labeling seen after caudal area 1--2 and SII injections differed only in its rostro--caudal extent within VPLm. SII injections generally resulted in labeling along the full rostro--caudal dimension of VPLm. A differential organization of the anatomy of thalamocortical projections to the various subdivisions of SI and to SII was noted in this study. It is postulated that the multiple, discrete patches of degeneration in laminae IIIb and IV of SI represent a portion of the somatosensory cortical columns and that the HRP-labeled clusters seen in VPLm following area 3b and rostral area 1--2 are the subcortical equivalents of these subcolumns.

Afferent Pathways

Subfornical organ efferents to neural systems for control of body water.

The subfornical organ, a circumventricular structure of the central nervous system, has efferent neural projections to sites within the brain known to be involved in drinking behavior and secretion of antidiuretic hormone. By using anterograde tracing techniques, it is shown that the subfornical organ projects to the nucleus medians of the medial preoptic area, to the organum vasculosum of the lamina terminalis, and to the supraoptic nuclei bilaterally. Its efferent connectivity is confirmed by retrograde transport of horseradish peroxidase. The organum vasculosum of the lamina terminalis, another circumventricular organ and a suspected receptor site for angiotensin II, is involved in the circuitry of the subfornical organ and also has an efferent projection to the supraoptic nuclei.

Animals

Efferent projections of the gracile nucleus in the cat.

The efferent projections of different portions of the gracile nucleus in the cat were studied using both autoradiographic and degeneration tracing methods. The results suggest that there are two aspects to the functional organization of these projections. First, the somatotopic organization of the gracile n. (GR) is maintained, but inverted, by the topographic organization of its projections to VPL1. Fibers from the lateral portions of GR terminate medially in VPL1; fibers from the dorsal portions terminate ventrally. These fibers, especially those from the middle and caudal portions of GR, terminate in dense, precisely located groups of clusters. Dorsally located clusters in VPL1 (predominantly from middle-ventral portions of GR) are significantly smaller than ventrally located clusters (predominantly from middle-dorsal portions). The second aspect of this organization, involving the projections both to VPL1 and to other brain stem targets, is that some kind of functionally relevant sorting process appears to occur as fibers leave different portions of the gracile n. The afferent projections of the rostral (GRr) and middle-ventral portions (GRmv) of the gracile n. are different from those from the other portions of the nucleus. Projections to VPL1 from GRr are less dense, less likely to form clusters, less clearly topographically organized, and extend further rostrally and dorsally in VPL1 than those from the rest of GR. The clusters are small, like those from GRmv. Similarly, although all portions of GR project to several other brain stem regions, these projections appear to be derived preferentially from GRr and/or GRmv. These brain stem regions involve certain portions of the inferior olive, inferior and superior colliculi, red n., zona incerta, pretectum, thalamic posterior group and the H field of Forel. This dual organization of efferent connectivity is similar to that of the cuneate n.20, and is consistent with many of the differences in cytoarchitecture, afferent connectivity and response properties of cells within different portions of the dorsal column nuclei.

Animals

Projections to the inferior olive of the cat. II. Comparisons of input from the gracile, cuneate and the spinal trigeminal nuclei.

The present experiments compared the projections to the inferior olive of the cat from the gracile, cuneate and spinal trigeminal nuclei. A differential labeling strategy was used for these comparisons. It was found that all three somatic sensory nuclei project to portions of all three major divisions of the contralateral inferior olive. The spinal trigeminal n. may also project less densely to the ipsilateral medial accessory olive. Projections to the dorsal accessory nucleus (DAO) and the medially-adjacent ventral lamella of the principal nucleus are roughly somatotopically organized. Although there is considerable overlap between the projection zones, the gracile n. projects predominantly to lateral DAO, the cuneate n. projects predominantly to medial DAO, and the spinal trigeminal nucleus pars caudalis projects predominantly to the most medial portions of DAO and the ventral lamella of principal olive. Projections to the medial accessory olive, on the other hand, are not as highly organized. Instead, they overlap extensively within a small egg-shaped area in the middle of the caudal half of the nucleus. Whereas all portions of the gracile and cuneate nuclei project to the inferior olive, only the pars caudalis of the spinal trigeminal nucleus appears to do so. These results were compared with the three available olivocerebellar maps as well as with the available behavioral and electrophysiological evidence on cerebellar somatotopic organization. This comparison indicated that the inputs to the cerebellum from the three second-order somatosensory nuclei via the inferior olive appear to be generally consistent with cerebellar somatotopic organization. This consistency is apparent not only with respect to the longitudinally-organized, vermal and paravermal differences in the anterior lobe, but also with respect to the transversely-organized specific somatotopy of the intermediate zone of the anterior lobe and the paramedian lobule.

Animals

The efferent connections of the feline nucleus cuneatus.

Nucleus cuneatus projections to nucleus ventralis posterolarteralis pars medialis (VPLm) and other thalamic as well as midbrain and medullary nuclei were studied in cats using the Fink-Heimer I silver technique. Single electrolytic lesions of very small size were made stereotaxically in different zones of nucleus cuneatus under electrophysiological control. All zones studied projected to contralateral VPLm in a pattern of discrete terminal arborizations or clusters, which were organized in onionskin-like dorso-ventral laminae. The clusters of degeneration varied in size and density according to their dorsoventral location within VPLm. Those in dorsal areas were smaller in diameter (50-125 mu) and contained less dense amounts of degeneration than clusters (150-300 mu) in more ventral regions. The clustered terminal arborizations mirrored the organization of the VPLm neuronal clusters, themselves. Terminations within VPLm were topographically organized, but were completely inverted, i.e. dorsal nucleus cuneatus projected to ventral VPLm and ventral to dorsal, lateral to medial, and medial to lateral VPLm. A ventral zone of nucleus cuneatus, which contained "deep" units, projected to a separate dorsal zone of VPLm. In addition to its classical connection with VPLm, nucleus cuneatus projected to the following contralateral brainstem or thalamic nuclei: medial and dorsal accessory olives, external nucleus of the inferior colliculus, ventrolateral part of the superior colliculus, nucleus ruber, medial geniculate nucleus pars magnocellularis, suprageniculatus, medial and lateral divisions of the posterior thalamic nuclear group, zona incerta, and Fields of Forel. Very sparse amounts of degeneration were also present within nuclei ventralis posteromedialis (caudal pole) and ventralis posterolateralis pars lateralis. The brain-stem and thalamic projections of the dorsocaudal part (cell nest region) of the cuneate nucleus were more restricted than those of its rostral and ventral regions. The clusters of both the VPLm neurons and cuneate terminations within VPLm provides an anatomical basis for the functional characteristics of synaptic security, fine grain somatotopia and modality specificity so prominent in the dorsal column nuclei-medial lemniscal system.

Animals