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Biomedical subjects

F R Sharp

Publications and source records attributed to F R Sharp.

At least 73 records · Page 4Linked to original sources

Quantitative measurement of interresponse times to assess forelimb motor function in rats.

Eight rats were trained to use their left paw to rapidly press the right lever of an operant chamber once and the left lever twice to obtain a food reward. Between-levers interresponse times and same lever interresponse times were measured daily for several weeks before and after bilateral removal of frontal motor/sensory cortex. This surgery resulted in a permanent deficit in most rats' ability to rapidly alternate between levers, but resulted in only a temporary deficit in their ability to rapidly press the same lever. Sham surgery and removal of hindlimb motor cortex had little immediate effect on interresponse times. The data demonstrate that sequential motor behavior tested in the between-levers tasks is chronically affected by cortical lesions, but the speed of the same repetitive movement tested in the same lever task is not. Measuring the time to rapidly alternate between two different levers, therefore, provides a quantitative method for measuring acute and chronic forelimb motor deficits due to motor cortex injury in rats which could be applied to any mammal.

Animals

Adult rat motor cortex connections to thalamus following neonatal and juvenile frontal cortical lesions: WGA-HRP and amino acid studies.

Frontal cortex was removed in 1- and 30-day-old rats. When both groups reached 90 days of age, the forelimb motor/sensory cortex in the unlesioned hemisphere was injected with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or tritiated leucine. Thalamic neurons were retrogradely labeled only ipsilateral to the WGA-HRP injection site in both neonatally and juvenile-lesioned subjects. Ventrolateral (VL), ventromedial (VM), centromedial (CM), centrolateral (CL), parafascicular (PF), posteromedial (POm), and posterior (PO) thalamic nuclei were labeled. This and the demonstration of only ipsilateral thalamocortical connections at birth helped explain the marked thalamic atrophy which developed ipsilateral to neonatal frontal cortex lesions. Death of thalamic neurons after neonatal removal of their normal cortical target could be due to their failure to sprout into the opposite cortex because that cortex was already innervated by the opposite thalamus at birth. Leucine motor/sensory cortex injections in both neonatally and juvenile-lesioned subjects labeled the ipsilateral VL, VM, CM, CL, PF, POm, and PO thalamic nuclei; contralateral CM, CL, and PF thalamic nuclei; ipsilateral medial, ventral, and lateral pontine nuclei; and parts of the contralateral pontine nuclei. The ipsilateral connections were always more robust than the contralateral connections. The contralateral corticothalamic and corticopontine projections, however, were much more numerous and widespread in neonatally compared to juvenile-lesioned subjects. The greater sparing of some motor functions said to occur in neonatal compared to adult motor cortex-lesioned subjects could be due to the plasticity of corticothalamic, corticopontine, and other corticofugal pathways, but not to the plasticity of thalamocortical pathways.

Age Factors

Relation of HTLV-III seropositivity and lymphadenopathy.

Testing for antibody to human T-lymphotropic retrovirus (HTLV-III) was carried out in five groups of homosexual men: 250 without lymphadenopathy (control group), 37 with slight or nonpersistent lymph node enlargement (intermediate group), 141 with persistent generalized lymphadenopathy, 32 with persistent generalized lymphadenopathy who underwent biopsy and 11 in whom acquired immune deficiency syndrome (AIDS) was diagnosed. The rates of HTLV-III seropositivity in the five groups were 18%, 32%, 61%, 94% and 91% respectively.

Acquired Immunodeficiency Syndrome

Multiple vibrissae sensory regions in rat cerebellum: a (14C) 2-deoxyglucose study.

Repetitive tactile sensory stimulation of the right mystacial vibrissae (whiskers) was performed in awake, adult rats. Regions of increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically in cerebellum. Predominantly ipsilateral activation of multiple discrete granule cell regions occurred in paramedian lobule, crus 2, crus 1, lobulus simplex, and anterior lobe hemisphere. Bilateral and contralateral activation of cerebellum did occur. Multiple small patches, as well as large granule cell regions, were activated. Mossy fiber afferents from the spinal trigeminal nuclei (particularly interpolaris), principal trigeminal sensory nucleus, and superior colliculus could account for metabolic activation of the granular layer. The slight metabolic activation of the molecular layer could have occurred from climbing or parallel fibers. Comparisons of the paramedian lobule granule cell regions activated during repetitive sensory stimulation of the vibrissae (RSSV) to those activated during vibrissae motor cortex stimulation (VMIS) showed regions only activated by RSSV, regions only activated by VMIS, and regions activated by both RSSV and VMIS. The granule cell regions activated during RSSV and VMIS were usually adjacent to or overlapping each other. Regions only activated during RSSV or only during VMIS could represent technical problems in trying to compare vibrissae motor and sensory pathways in two different groups of animals. Alternatively, cerebellar regions activated only during RSSV could process vibrissae tactile inputs. Regions activated only during VMIS could process vibrissae motor and perhaps proprioceptive sensory input. Regions activated during both RSSV and VMIS might process vibrissae proprioceptive sensory input and/or might represent loci where vibrissae motor, proprioceptive sensory, and tactile sensory convergence occur. The results raise the possibility that vibrissae motor, proprioceptive sensory, and tactile sensory pathways could be processed in separate granule cell patches in parts of cerebellum and in the same granule cell patches in other parts of cerebellum.

Afferent Pathways

Vibrissae tactile stimulation: (14C) 2-deoxyglucose uptake in rat brainstem, thalamus, and cortex.

The right mystacial vibrissae of awake, adult rats were stroked at 4-6 times/second and brain regions which increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically. The ventral parts of the ipsilateral spinal trigeminal nuclei pars caudalis (Sp5c), pars interpolaris (Sp5i), pars oralis (Sp5o), and the principal trigeminal sensory (Pr5) nuclei were activated. The lateral part of the ipsilateral facial (VII) nucleus (the region which innervates the vibrissae muscles) was also activated possibly via excitatory, trigeminal (Sp5c, Sp5i, Sp5o, Pr5) sensory afferents. A number of regions were activated contralateral to the sensory stimulus. Discrete patches of (14C) 2DG uptake occurred in deep layers of the superior colliculus (SCsgp). Dorsolateral and dorsomedial parts of the ventrobasal nucleus (VB), and posterior, dorsolateral parts of the reticular nucleus (R) of thalamus were activated, along with broad portions of the primary somatosensory cortex (SI) and second somatosensory cortex (SII). Though all layers of SI and SII cortex increased 2DG uptake, VB thalamic afferents to layers IV and Vc-Vla presumably accounted for the greater activation of these cortical layers during repetitive sensory stimulation of the vibrissae (RSSV). Activation of the above structures fits well with known anatomical data. However, the pattern of activation during RSSV was very different from that previously described during vibrissae motor cortex stimulation (VMIS). RSSV and VMIS both produced similar repetitive movements of all the mystacial vibrissae. However, only a few overlapping brain regions were activated during both RSSV and VMIS. These RSSV-VMIS overlap zones included Sp5o; rostral Sp5i; lateral VII; SCsgp; ventrobasal-posteromedial and ventrobasal-ventrolateral zones in thalamus; and a rostral region of SI probably anterior to the Woolsey vibrissae barrelfield in the dysgranular somatosensory (SI) cortex. Since RSSV and VMIS would both be expected to activate vibrissae proprioceptors, we have hypothesized that vibrissae proprioceptive input was processed in part in the RSSV-VMIS overlap zones. Convergence of motor-sensory inputs and other types of processing could have also occurred in these overlap zones.

Animals

Lithium effects on selected circadian rhythms in rats.

Treating rats with lithium results in clear phase-delays in certain circadian rhythms but has no effect upon other rhythms. Phase-delays can be seen in running-wheel activity rhythms but under certain conditions, phase changes are not noted in SCN 2-DG uptake or pineal melatonin rhythms.

Animals

Autoradiographic maps of regional brain glucose consumption in resting, awake rats using (14C) 2-deoxyglucose.

The 2-deoxy-D-[14C]-glucose (2-DG) autoradiographic method for determining regional brain glucose consumption has been applied successfully by a number of workers for mapping the alterations of brain glucose consumption which occur in association with experimental alterations of brain functional activity. This paper provides a framework for the interpretation of these and further studies by presenting: (1) the pattern of regional brain glucose consumption in the normal, resting, awake rat; (2) the anatomical identities of brain structures which on autoradiographs appear only as regional variations of optical density. For this purpose, a series of 2-DG autoradiographs of coronal brain sections from an injected animal is compared with adjacent labeled Nissl sections.

Animals

Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat.

An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states.

Animals

Rotation induced increases of glucose uptake in rat vestibular nuclei and vestibulocerebellum.

A new technique for the autoradiographic measurement of regional cerebral glucose consumption using tracer amounts of radioactive 2-deoxyglucose (2-DG) was employed to study the effects of vestibular inputs on local cerebral glucose metabolism. Rats rotated in the vertical plane showed localized increases of glucose utilization in the vestibular nuclei and several areas of the cerebellum: flocculus, nodulus, ventral uvula, and accessory paraflocculus. The changes in the cerebellum occurred both in the neuronal perikarya-rich granular layer and the neuropil-rich molecular layer. Differential changes resulting from rotation occurred within the granular layer of the nodulus, where at least 7 separate longitudinal zones of differing glucose consumption were seen. This type of longitudinal organization has been described previously in other areas of the vermis with other techniques.

Animals