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PubMed1981

Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: the climbing fiber system.

In cerebellum, the evoked responses of the Purkinje cell to both excitatory and inhibitory afferent input have previously been shown to be enhanced by local iontophoresis of norepinephrine (NE). The influence of locus coeruleus (LC) conditioning stimulation on Purkinje cell responses to climbing fiber input was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar potentiative effects. Stimulation of LC, at intensities which by themselves were subthreshold for directly affecting background activity, markedly enhanced complex spike excitation of Purkinje cells elicited by activation of climbing fiber inputs from sensorimotor cortex. Depressant responses observed after complex spike excitation were also augmented by the LC conditioning. Iontophoretic application of sotalol, a specific beta-adrenergic receptor blocker, reversibly antagonized this facilitation of climbing fiber-evoked responses. In addition, the potentiative effects of LC stimulation were not observed after destruction of NE-containing axons and terminals in cerebellum by 6-OHDA. These results suggest that noradrenergic input from the LC can enhance the efficacy of climbing fiber synaptic action on the Purkinje cell, and are thus consistent with the hypothesis of a 'modulatory' role rather than a specific information transfer function for NE in cerebellum.

Afferent Pathways↗
PubMed1981

Effect of oxotremorine on local cerebral glucose utilization in motor system regions of the rat brain.

The [14C]2-deoxy-D-glucose technique was used to test the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in rats. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.7 mg/kg, ip) increased LCGU in brain regions involved in motor function: the sensorimotor cortex; the extrapyramidal motor system, including the striatum, globus pallidus, red nucleus, substantia nigra, subthalamus and ventral nucleus of the thalamus; the cerebellar vermis, fastigial nucleus and nucleus interpositus; and the vestibular nucleus. No effects were observed in the fibers of the pyramidal tract, internal capsule, cerebellar white matter and the dentate nucleus. Increases were not affected by methylatropine (1 mg/kg sc), but were completely antagonized by scopolamine (2.5 mg/kg, ip). The anatomic distribution and magnitude of the LCGU response to OXO were not simply correlated with the reported densities of muscarinic receptors.

Animals↗
PubMed1981

Connections of the subthalamic nucleus in the monkey.

Attempts were made to determine the afferent and efferent connections of the subthalamic nucleus (STN) in the monkey using retrograde and anterograde axoplasmic transport technics. Following HRP injections limited to the STN, label was transported to arrays of cells adjacent, and parallel, to the lateral medullary lamina in the rostral two thirds of the lateral pallidal segment (LPS). Only sparse label was transported to cells of the pedunculopontine nucleus (PPN) and the locus ceruleus (LC). No enzyme was transported across the midline, or to the striatum, medial pallidal segment (MPS), thalamus, substantia nigra (SN) or dorsal nucleus of the raphe (DNR). HRP injected into portions of both the STN and SN produced retrograde transport of the enzyme to cells in parallel arrays in the LPS related rostrocaudally to the injection site. Additional enzyme transport was seen in cells of the striatum, the DNR and the PPN. Only a few isolated cells were labeled in the sensorimotor cortex. Efferent connections of the STN were studied in monkeys in which [3H]amino acids were injected hydraulically or iontophoretically into the STN. Isotope traced in serial autoradiographs was distributed to: (1) both segments of the globus pallidus (GP) in arrays parallel to the medullary laminae, and (2) the pars reticulata of SN (SNpr). The greatest number of terminals was found in the MPS. Fibers from the rostral part of the STN descended along the dorsal border of the SN and projected ventrally to terminations in the SNpr. No isotope was transported across the midline, or to the striatum, thalamus, DNR or PPN. Isotope injected into both the STN and SN produced similar transport to the GP and transport via nigral efferent fibers to: (1) portions of the striatum, (2) specific thalamic nuclei (VAmc, VLm, DMpl), (3) deep and middle gray layers of the superior colliculus and (4) PPN. Control studies indicated that [3H]amino acids injected only into the SN were transported to PPN. HRP injected into PPN produced profuse retrograde transport in cells of the MPS and SNpr and distinct label in a few cells of the zona incerta and STN. These data suggest that the STN receives its major subcortical input from cell of the LPS arranged in arrays which have a rostrocaudal organization. No cells of the MPS or SN project to the STN. The output of the STN is to both segments of the GP and SNpr. Major subcortical projections to PPN arise from the MPS and SNpr, but afferents also arise from other sources. The major projection of PPN is to SN.

Animals↗
PubMed1982

A re-evaluation of the question of ascending fibers in the pyramidal tract.

In 1952 we published a study in the cat with the Glees method, demonstrating the occurrence of degenerating fibers in the pyramidal tract rostral to transections of the tract in the spinal cord. These fibers were interpreted as spinocortical fibers, which have also been described in man. However, other authors have disputed the existence of such fibers. In an attempt to provide more information about this subject, multiple injections of horseradish peroxidase (free and lectin-labeled) were made in the sensorimotor cortex of 4 cats. No retrogradely labeled cells were found in the spinal cord in these cases. Our present and previously reported findings are discussed in the light of other studies of pathological changes in fiber tracts within the central nervous system. Although the present experiments were negative, the degenerating axons previously observed by us in silver sections from the pyramid, pons and internal capsule after lesions of the pyramidal tract in the spinal cord, can not be satisfactorily explained as evidence of retrograde, indirect Wallerian, degeneration of corticospinal fibers.

Animals↗
PubMed1982

Ethanol-withdrawal syndrome associated with both general and localized increases in glucose uptake in rat brain.

Glucose uptake was studied in the brains of rats undergoing an overt ethanol-withdrawal syndrome by 2-deoxy-D-[14C]glucose autoradiography. In addition to a general increase in glucose uptake, localized alterations were observed in sensorimotor cortex, globus pallidus, thalamus and cerebellum. The results suggest that the ethanol-withdrawal syndrome is associated with a general increase in glucose metabolism as well as localized increases in functionally distinct regions of sensory and motor brain regions.

Alcoholism↗
PubMed1982

A quantitative study of synaptic reorganization in red nucleus neurons after lesion of the nucleus interpositus of the cat: an electron microscopic study involving intracellular injection of horseradish peroxidase.

A quantitative electron microscopic analysis of the corticorubral projection was performed in the red nucleus (RN) of adult cats to determine morphological correlates of synaptic reorganization that occur following a lesion of the interpositus nucleus (IP). Corticorubral synaptic endings were identified by lesioning the sensorimotor cortex 2-6 days before electrophysiological experiments. Horseradish peroxidase (HRP) was injected into electrophysiologically identified RN neurons. Sagittal sections 100 micrometers thick were cut and reacted by diaminobenzidine. Sections containing HRP-positive neurons were selected and embedded in Epon. In normal cats, degenerating corticorubral terminals in the RN region frequently made contact with dendritic profiles, having small cross-sections, while a few made contact with somatic profiles. Similar results were obtained when degenerating terminals making contact with HRP-filled dendrites were analyzed. In the experimental animals, the cortical lesion was performed more than 8 weeks after lesion of the IP. In these animals, degenerating corticorubral terminals were frequently found on proximal dendrites and somata in RN region and HRP-positive neurons in contrast to the findings in normal cats. The results indicate that new corticorubral synapses were formed on proximal dendrites and somata of RN neurons as a consequence of IP lesions.

Animals↗
PubMed1982

Sensorimotor cortical projections to the marginal zone of the trigeminal subnucleus caudalis.

An ultrastructural investigation of the marginal zone (lamina I) of the spinal trigeminal subnucleus caudalis was carried out in 7 adult cats at 30 h through 7 days after ablations of face area of the contralateral sensorimotor cortex. Corticofugal boutons were observed to undergo electron-dense degeneration in the marginal zone beginning 4 days after the cortical lesion. These boutons were small (1--2 micrometers), widely dispersed and made synaptic contacts onto small dendrites or dendritic spines. These new observations indicate that cortical inhibition and facilitation of ascending orofacial sensation may be mediated in part by a direct pathway to the marginal zone.

Animals↗
PubMed1982

Trigeminal evoked potentials: origins in the cat.

Short latency brain stem (far-field) and cortical (early-field) potentials were evoked by stimulation of the main nerve epidurally over the primary sensorimotor cortex. The specific generators of these volume conducted potentials were identified from both lesion and recording studies in the trigeminal lemniscal system. Far-field components I, II and III, respectively, originate from the semilunar ganglion, trigeminal lemniscus and thalamocortical radiation; whereas early near-field components P1 and N1 originate from the cortical cell layers.

Action Potentials↗
PubMed1982

Study of the neural basis of circling behavior induced by L-dopa in lesioned entopeduncular cats.

Experiments were carried out in cats bearing unilateral electrolytic lesion of the entopeduncular nucleus. The animals were tested for circling 1-2 weeks after surgery. Postoperatively the cats displayed transient spontaneous ipsiversive turning. The administration i.p. of L-DOPA (80 mg/kg) plus CarbiDOPA (30 mg/kg), suspended in 10% Tween 80, induced rotational behavior toward the lesioned side. This effect began about 26 min after drug administration and reached its maximum 40-110 min after the injection. Electrolytic lesions placed in the superior colliculus, strionigral pathway or pedunculopontine nucleus, contralateral to the lesioned entopeduncular nucleus did not modify the circling behavior induced by L-DOPA. Similar results were observed following unilateral lesion of the sensorimotor cortex or the VL thalamic nucleus. These results suggest that the circus movements induced by L-DOPA, in animals with unilateral lesion of the entopeduncular nucleus, is not mediated by the classic outflow of the striopallidal system.

Animals↗
PubMed1983

High resolution radioautographic investigation of [3H]GABA accumulating neurons in cat sensorimotor cortical areas.

After the injection of [3H]GABA in the cat sensorimotor cortex, radioautographic analysis of thick and thin sections showed an intense labeling of numerous nerve fibers and of some neuronal cell bodies. Labeled boutons displayed either only clear vesicles or clear and large granular vesicles. They could constitute symmetrical synaptic differentiations upon dendrites or dendritic spines. Radioactive perikarya of stellate neurons could be labeled either by direct uptake or by retrograde axonal flow.

Animals↗
PubMed1983

Properties of cerebello-precerebellar reverberating circuits.

Intracellular recordings were made from neurons of the red nucleus (RN) in cats where the cerebellar cortical effects were removed by chronic ablation of the intermediate part of the anterior lobe of the cerebellum. A prolonged depolarization could be elicited by stimulating the nucleus interpositus (IP) of the cerebellum, nucleus reticularis tegmenti pontis (NRTP) and the nucleus reticularis paramedianus (PMRN). This prolonged depolarization was abolished after cooling the inferior and middle cerebellar peduncles and persisted after ablation of the cerebral sensorimotor cortex. The prolonged depolarization was also recorded intracellularly from IP neurons. It was concluded that the prolonged depolarization set up in RN neurons is due to the repetitive discharges of IP neurons which produces tonic bombardment onto RN cells. The mechanisms of the repetitive discharges of IP neurons are considered to be due to impulse reverberation via the IP. The dynamic properties of the reverberating circuits were characterized by regenerative behavior. Above and below threshold, there were two states, the excited state where many constituent neurons were active, and the resting state where all neurons were inactive. It was found that cats with chronically stimulated cerebral peduncle (CP), and tested in an acute experiment, showed sometimes effective for inducing the prolonged depolarization and repetitive discharges of RN neurons by stimulation of IP. The prolonged depolarization thus produced could be reversibly abolished by cooling the middle and inferior cerebellar peduncles. The possible constituent neurons of the reverberating circuits were investigated in light of previous physiological investigations of stimulating the NRTP, PMRN, nucleus reticularis lateralis (LRN), nucleus olivaris inferior (IO) and recording EPSPs in RN cells. The RN cells receive axon reflex activation from NRTP and PMRN, and disynaptic excitation from NRTP, PMRN, LRN and IO. Based on these and other available data, the components of the cerebello-precerebellar reverberating circuits are discussed.

Animals↗
PubMed1984

Glucose utilization is unchanged in red nucleus after axotomy.

Separate series of adult rats were subjected to unilateral high cervical and low thoracic section of the rubrospinal tract and sacrificed 1-30 (cervical series) and 3-100 days (thoracic series) later. Local cerebral glucose utilization ([14C]2-DG method of Sokoloff et al.) was determined in the red nucleus and in the inferior colliculus, nucleus interpositus and sensorimotor cortex of both sides in operates and controls. Although severe atrophy of rubral neurons follows cervical tractotomy while reversible chromatolytic alterations occur after thoracic lesions, glucose utilization did not differ in the red nucleus of operated and control rats. However, glucose utilization increased slightly in the inferior colliculus of all operated animals, a finding of indeterminate significance. The failure of axotomized intrinsic neurons of red nucleus and their surround to show altered glucose utilization stands in sharp contrast to the marked increase which occurs in cranial nerve nuclei after axotomy of their contained extrinsic neurons. The data are held to constitute another indication that there is a fundamental difference in the metabolic responses of extrinsic and intrinsic mammalian neurons to axotomy and may support the contention that, in mammals, the axon reaction of intrinsic neurons is fundamentally different from that of extrinsic nerve cells. This difference may have significance for failure of axon regeneration in mammalian CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Reorganization of corticorubral synapses following cross-innervation of flexor and extensor nerves of adult cat: a quantitative electron microscopic study.

A quantitative electron microscopic study of corticorubral synapses was performed in the red nucleus (RN) of adult cats to determine the morphological correlates for the changes in time course of corticorubral excitatory post-synaptic potentials, which occur following cross-innervation of forelimb extensor and flexor nerves. Corticorubral synaptic endings were identified by anterograde degeneration after lesions of the ipsilateral sensorimotor cortex. Rubrospinal neurons innervating upper spinal segments were electrophysiologically identified and filled with horseradish peroxidase (HRP). These cells were mainly situated in the dorsomedial part of RN. Electron micrographs of the degenerating corticorubral synaptic endings were taken in the region surrounding HRP-filled neurons and the diameter of the dendrites contacted by such terminals was measured. In the cross-innervated animals many degenerating terminals were found to synapse on dendrites with large diameter and the somata of neurons in RN. This is in contrast to the previous observations in normal cats, in which very few corticorubral synapses were found to synapse on proximal dendrites and somata of RN neurons. The diameter of HRP-filled neurons in cats which were cross-innervated was slightly smaller than those observed in normal animals. These results indicate that new corticorubral synapses were formed on proximal dendrites and somata of RN neurons as a consequence of cross-innervation.

Animals↗
PubMed1985

Differential corticospinal projections in the cat. An autoradiographic tracing study.

An autoradiographic study of the corticospinal projections from different parts of the cat sensorimotor cortex produced the following findings. The lateral part of area 4 projects contralaterally to the lateral intermediate zone of the cervical enlargement only. The intermediate part of area 4 projects throughout the spinal cord, contralaterally to the lateral part of the intermediate zone and bilaterally to its ventromedial part. The lateral and medial part of area 3 project contralaterally to the cervical and lumbosacral dorsal horn (including laminae I and II), respectively.

Animals↗
PubMed1985

Local cerebral glucose utilization in the free moving mouse: a comparison during two stages of the activity-rest cycle.

The 2-deoxy-D[1-14C]glucose ([14C]DG) technique has been applied to the free moving mouse for the quantitative determination of local cerebral glucose utilization (LCGU). Reproducible values for LCGU were obtained indicating that the [14C]DG method had a sufficient resolution power to allow visualization and quantification of very small structures provided that glucose and [14C]DG plasma concentrations were measured on microsamples, autoradiographs prepared from proper tissue sections and suitable techniques used for analysis of the maps thus obtained. LCGU was measured in free moving mice during two stages of the light-dark cycle, one corresponding to a period of rest and the other to a period of high motor activity. In the two groups of animals LCGU was heterogeneous in the grey matter, the highest values being found in the auditory regions, the cerebellar and vestibular nuclei. LCGU was found to be lower in drowsy animals during the day than in active animals during the night and the difference was significant in the 8 following structures: the sensorimotor cortex, the septal nuclei, the nucleus of the olfactory tract, the basal amygdaloid nucleus, the ventral nucleus of the thalamus, the lateral geniculate body, the medial geniculate body and the auditory cortex. On the contrary, the suprachiasmatic nucleus was very active during the day and relatively inactive during the night as previously reported in the rat.

Animals↗
PubMed1986

The induction and modification of voltage-sensitive responses in cat neocortical neurons by N-methyl-D-aspartate.

The actions of the excitatory amino acid, N-methyl-D-aspartate (NMDA), on layer V neurons of cat sensorimotor cortex were examined in an in vitro slice preparation using current clamp, single electrode voltage clamp (SEVC), and ionic substitution techniques. Low doses of NMDA evoked a slow depolarization with a net decrease of input conductance. Larger doses additionally evoked repetitive firing, rhythmic depolarization shifts (DSs), low-threshold calcium spikes (in the presence of TEA+) and bistable membrane potential behavior. Ionic substitution experiments suggested that entry of both Ca2+ and Na+ ions contributed to the NMDA responses. Attention was focused on the NMDA response with Ca2+ entry blocked. Examination by SEVC revealed that, in both normal cells and in the presence of several blocking agents, NMDA induced a highly voltage-dependent inward ionic current which could result in a region of negative slope conductance on the cell's current-voltage relation. The development of this current seems capable of accounting for all aspects of the observed response, including the DSs and low-threshold Ca2+ spikes. Substitution of TEA+ for most external Na+ (with Ca2+ entry blocked) largely eliminated the NMDA responses and corresponding ionic current. Our results in neocortical neurons are compared to those recently obtained in cultured murine neurons.

Animals↗
PubMed1986

Non-neuronal cell proliferation in tissue culture: implications for axonal regeneration in the central nervous system.

A tissue culture model has been developed to examine the hypothesis that proliferating non-neuronal cells may constitute a physical and/or chemical barrier to regenerating neurons in the central nervous system. Explants from the sensorimotor cortex of 20-day-old fetal rats were cultured in serum medium (control) or serum medium containing 10(-5) M cytosine arabinoside (AraC), a mitotic inhibitor, for varying periods: 2-10, 4-12, 4-10, 4-8 and 4-7 days in vitro (DIV). The center and outgrowth zone of the explants were examined by phase-contrast microscopy at varying intervals between 3 and 18 DIV. The extent of central degeneration was greatest in explants treated with AraC from 2 DIV, and was least in the 4-7 day treated group in which only minimal degeneration was evident at 13 and 18 DIV. In the outgrowth zone at 18 DIV non-neuronal cell proliferation was controlled in the 4-10 day treated explants, although this was accompanied by extensive degeneration of neurites. Further examination of neurite viability, using a neurite viability ratio, revealed that degeneration was first evident at 6 DIV in the 2-10 day treated explants, but not until 9 or 13 DIV in any of the explants exposed to AraC from 4 days onwards. There was minimal degeneration in the 4-7 day treated explants. Electron microscopic examination revealed the presence of atypical inclusions in non-neuronal cells of 4-8 day treated explants, suggesting that the cytotoxic effect of AraC may be due to a disturbance in lipid and/or ganglioside metabolism. Quantitative electron microscopic analysis of the outgrowth zone at 18 DIV revealed a significant increase in the summated area of neuronal tissue (from 7 to 18 microns2/100 microns2) and a decline in the summated area of non-neuronal cells (from 83 to 61 microns2/100 microns2) for explants treated with AraC from 4 to 7 DIV compared to control. Diminishing the potential of non-neuronal cells to act as a barrier by controlling their proliferation may, therefore, be of importance in enhancing the regenerative response of central neurons.

Animals↗
PubMed1987

Electrophysiological studies on the specificity of the cholecystokinin antagonist proglumide.

Recent evidence suggests that the glutaramic acid derivative proglumide (PROG) is a selective antagonist of cholecystokinin (CCK) in the rat CNS. The extent of this selectivity has now been characterized in more detail. Iontophoretic or intravenous (i.v.) administration of PROG was ineffective against the excitatory effect of iontophoretically applied neurotensin on midbrain dopamine (DA) cells, the excitatory effect of substance P and the inhibitory effect of Met-enkephalin on prefrontal cortical neurons, and the inhibitory effect of histamine on neurons of the sensorimotor cortex. In contrast, PROG blocked the excitatory effect of the C-terminal octapeptide of CCK in all 3 areas. Furthermore, iontophoretic PROG diminished, whereas CCK enhanced the inhibitory effect of similarly applied DA and GABA on DA cells. PROG pretreatment (1 mg/kg, i.v.) reduced the inhibitory potency and maximum effect of i.v. apomorphine (APO) on A9 DA neurons, while the inhibitory potency of APO was enhanced by i.v. CCK. Pretreatment with PROG plus CCK resulted in APO effects which were no different from those after PROG alone. Chronic treatment with PROG (1 mg/kg, p.o., 21 days) resulted in a return to normal of DA cell APO sensitivity. Combined, these findings suggest that PROG may be a relatively selective CCK antagonist, that the functional effect of dendritically released DA may be influenced by endogenously released CCK, and that tolerance may develop to the effects of chronic CCK receptor blockade.

Action Potentials↗