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PubMed2001

Functional correlates of pallidal stimulation for Parkinson's disease.

We measured regional cerebral blood flow with H2 15O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right-handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication-free state. Internal globus pallidus deep brain stimulation improved off-state United Parkinson's Disease Rating Scale motor ratings (37%, p < 0.002) and reduced timing errors (movement onset time, 55%, p < 0.01) as well as spatial errors (10%, p < 0.02). Concurrent regional cerebral blood flow recordings revealed a significant enhancement of motor activation responses in the left sensorimotor cortex (Brodmann area [BA] 4), bilaterally in the supplementary motor area (BA 6), and in the right anterior cingulate cortex (BA 24/32). Significant correlations were evident between the improvement in motor performance and the regional cerebral blood flow changes mediated by stimulation. With internal globus pallidus deep brain stimulation, improved movement initiation correlated with regional cerebral blood flow increases in the left sensorimotor cortex and ventrolateral thalamus and in the contralateral cerebellum. By contrast, improved spatial accuracy correlated with regional cerebral blood flow increases in both cerebellar hemispheres and in the left sensorimotor cortex. These results suggest that internal globus pallidus deep brain stimulation may selectively improve different aspects of motor performance. Multiple, overlapping neural pathways may be modulated by this intervention.

Adult↗
PubMed1990

Experimental studies of emmetropization in the chick.

The eyes of neonates grow from ametropia (refractive error) toward emmetropia. Whether or not this 'emmetropization' is visually guided is controversial. I describe experiments which demonstrate that in the chick refractive state is used to regulate the growth of the eye's vitreous chamber in order to achieve emmetropia from hyperopia or myopia that is induced by different visual deprivations. I discuss several studies that begin to examine the neural pathways that might be involved in the control of eye growth. Optic nerve section was used to examine the level of visual processing necessary for the control of eye growth. Eyes in which the optic nerve has been cut can still grow in the appropriate direction to correct induced hyperopia or myopia. Nevertheless, an intact optic nerve is necessary for normal refractions to be achieved; eyes with optic nerve section overshoot control levels and reverse the sign of the initial refractive error. These findings suggest that eye growth in chicks is controlled by an intraocular mechanism and possibly by a brain-mediated mechanism as well. The hypothesis that ocular accommodation is integral to the control of eye growth was also tested. Complete recovery from induced refractive errors was achieved even when accommodation had been abolished by lesions of the Edinger-Westphal nucleus. The elimination of accommodation did not prevent the ability of chick eyes to compensate for the defocus of spectacle lenses. These results suggest that accommodation is not necessary for the control of eye growth.

Accommodation, Ocular↗
PubMed1984

Afferent and efferent relationships of the basal ganglia.

A survey of the known circuitry of the basal ganglia leads to the following conclusions. (1) No complete account can yet be given of the neural pathways by which the basal ganglia affect the bulbospinal motor apparatus. Channels of exit from the basal ganglia originate from the internal pallidal segment, the pars reticulata of the substantia nigra, and the subthalamic nucleus, and each of these is directed in part rostrally to the cerebral cortex by way of the thalamus, in part caudally to the midbrain. The postsynaptic extension of the mesencephalic channels to bulbar and spinal motor neurons is largely unknown. Since the ascending channels are collectively of greatest volume, the notion remains plausible that the basal ganglia act in considerable part by modulating motor mechanisms of the cortex. (2) Recent findings in the rat suggest that the striatum is subdivided into a ventromedial, limbic system-afferented region and a dorsolateral, 'non-limbic' region largely corresponding to the main distribution of corticostriatal fibres from the motor cortex. These two subdivisions appear to give rise to different striatofugal lines, the outflow from the limbic-afferented sector partly re-entering the circuitry of the limbic system. (3) The limbic-afferented striatal sector suggests itself as an interface between the motivational and the more strictly motor aspects of movement. This suggestion is strengthened by evidence that the 'limbic striatum' seems enabled by its striatonigral efferents to modulate not only the source of its own dopamine innervation but also that of a large additional striatal region.

Animals↗
PubMed2007

Age-specific functions of stone handling, a solitary-object play behavior, in Japanese macaques (Macaca fuscata).

Stone handling (SH) in Japanese macaques, a form of solitary-object play, is newly acquired only by young individuals, and is the first example of a directly nonadaptive behavior that is maintained as a behavioral tradition within free-ranging provisioned social troops. We report here the first systematic investigation of this behavior in a stable captive social troop, the Takahama troop, which is housed in an outdoor enclosure of the Primate Research Institute (PRI), Kyoto University, Japan. This study was conducted to evaluate relevant competing hypotheses regarding the function of object play (e.g., misdirected foraging behavior and motor training) to explain the proximal causes and ultimate function(s) of SH. The "misdirected foraging behavior" hypothesis can be ruled out because of the lack of a clear temporal relationship between feeding and the occurrence of SH in any age class. Age-related differences in SH performance and behavioral patterns were observed, suggesting possible differences in the immediate cause and ultimate function between young and adults. Young individuals engaged in frequent bouts of short duration, involving locomotion and vigorous body actions throughout the day, which is typical for play by young in general. This pattern of behavior is consistent with the motor training hypothesis, which states that play occurs during the development of motor and perceptual skills and is thus potentially critical for neural and cognitive development. This practice is continued by those who acquire it at an early age, with adults engaging in significantly fewer but longer bouts that involve more stationary, complex manipulative patterns, almost exclusively in the late afternoon. We propose that for adults, at the proximate level SH is psychologically relaxing, but ultimately functions to maintain and regenerate neural pathways, and potentially helps to slow down the deterioration of cognitive function associated with advanced age in long-lived provisioned and captive macaques.

Aging↗
PubMed1987

Descending projections from the superior olivary complex to the cochlear nucleus of the cat.

Subdivisions of the cochlear nuclear complex give rise to a number of discrete projections to certain cell groups of the superior olivary complex and also received substantial descending projections from the periolivary nuclei. In the present study, we sought to determine by means of retrograde transport of horseradish peroxidase (HRP), and anterograde transport of radiolabeled protein, if the periolivary nuclei give rise to discrete projections to the various subdivisions of the cochlear nuclear complex. Following medium to large injections of HRP into the cochlear nucleus, irrespective of location, labeled cells were found in all periolivary nuclei bilaterally. In every case more than 40% of the labeled cells were found in the lateral nucleus of the trapezoid body on the same side and the ventral nucleus of the trapezoid body of both sides. Other periolivary nuclei contributing more than 5% of the total number of cells in individual cases were the contralateral lateral nucleus of the trapezoid body and the ipsilateral anterolateral and dorsal periolivary nuclei. Injections of tritiated leucine into periolivary nuclei gave rise to axonal labeling to the trapezoid body and the dorsal acoustic stria, usually bilaterally, and to terminal labeling that was widely distributed within the cochlear nuclear complex. In several cases with small injections, particularly in the lateral nucleus of the trapezoid body, the projections from the periolivary nuclei to the anteroventral and dorsal cochlear nuclei connected areas described as having similar best-frequency representation. The autoradiographic data corroborated the main results from the HRP experiments and provided additional information permitting these conclusions: the projections from the periolivary nuclei to the cochlear nuclear complex are organized tonotopically, at least in part; each periolivary nucleus (and perhaps individual cells), projects widely throughout the cochlear nuclear complex; the pattern of termination of projections from different periolivary nuclei to a given region of the cochlear nuclear complex are similar, as seen in autoradiograms, and the lateral and dorsal periolivary nuclei project mainly ipsilaterally, while the medial periolivary nuclei project bilaterally with a contralateral bias. The magnitude of these projections and their widespread distribution within the cochlear nuclear complex would suggest an important role for the descending projections in the normal functioning of the cochlear nucleus.

Acetylcholinesterase↗
PubMed1990

Immunolocalization and quantitation of a novel nerve terminal protein in spinal cord development.

In the adult spinal cord, the neuron-specific protein NT75 is located in nerve terminals synapsing in the superficial laminae of the dorsal horn. The present study examines the occurrence of NT75 in the developing rat spinal cord. NT75 immunoreactivity is detectable in primary afferent axons at the dorsal root entry zone on embryonic day 15. Subsequently, staining of presumptive nerve terminals appears in the deeper laminae of the dorsal horn, expanding into the superficial laminae during the first postnatal week. NT75 staining also appears in developing corticospinal tract axons in the brainstem at birth, and at lumbosacral levels by postnatal day 5. As NT75-positive nerve terminals approach the adult distribution, staining of primary afferent and corticospinal axons decreases, becoming undetectable by postnatal day 30. Dense transient staining of presumed nerve terminals in the ventral horn is also apparent during early postnatal development. Quantitative analysis of developing spinal cord shows a low level of NT75 immunoreactivity at birth. NT75 activity then increases substantially, reaching values by the third and fourth postnatal weeks up to 2.5 times that seen in adults. The occurrence of NT75 immunoreactivity correlates with the reported time course of synaptic development in the spinal cord. In addition, the results suggest that NT75 immunoreactivity is maintained at high levels in the nerve terminals of certain neural pathways into adulthood, whereas in other systems NT75 immunoreactivity may be detectable only during development.

Aging↗
PubMed1993

Intracellular injection of neurobiotin or horseradish peroxidase reveals separate types of preganglionic neurons in the sacral parasympathetic nucleus of the cat.

Sacral preganglionic neurons are essential to the neural control of the excretory and sex organs. Previously employed multi-cell tracing methods have certain limitations in the precise morphological analysis of the neural pathways that control these organs. These limitations were overcome by the intracellular injection of neurobiotin or horseradish peroxidase into single preganglionic neurons in the lateral sacral parasympathetic nucleus of the cat. Following light microscopic examination, these neurons, as a group, were found to have an average of five stem dendrites, which divided into 15 dendritic end-branches that were distributed among eight dendritic terminal fields. These dendrites had a major transverse orientation and were quite long, many of them reaching well into the dorsal and ventral horns and into the dorsal gray commissure. These dendrites also exhibited a major longitudinal orientation, extending an average of 869 microns (combined length of rostral and caudal dendrites) within the nucleus. Two groups of cells emerged on the basis of different dendritic patterns. Cells classed as Type I had dendrites in lamina I and in the ventral horn but lacked a significant projection into the lateral funiculus. Cells classed as Type II had major dendritic projections into the lateral funiculus but lacked dendrites in lamina I. The diverse dendritic patterns of these two cell types indicate dissimilar afferent control mechanisms and suggest that these preganglionic neurons may innervate different target organs.

Animals↗
PubMed1995

Nitric oxide-synthesising neurons in the central subnucleus of the nucleus tractus solitarius provide a major innervation of the rostral nucleus ambiguus in the rabbit.

We describe an intramedullary nitric oxide synthase (NOS) neural pathway that projects from the nucleus tractus solitarius (NTS) to the rostral nucleus ambiguus (NA) in the rabbit. With the use of NADPH diaphorase histochemistry and NOS immunohistochemistry, a compact group of NOS-positive perikarya was identified in the central subnucleus of the NTS dorsomedial to the tractus solitarius and rostral to the obex. A dense network of NOS terminals was seen in the rostral NA. We investigated whether NOS terminals in the NA derive from NOS perikarya in the central NTS and whether the central NOS pathway links esophageal afferents and efferents. In some rabbits, the central NTS was unilaterally lesioned. In others, Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected into the central NTS, or cholera toxin-gold was injected into the NA, or cholera toxin-horseradish peroxidase (HRP) was injected into the wall of the esophagus. The medulla was subsequently processed to demonstrate PHA-L, cholera toxin-gold, HRP, and NOS reactivity. Seven days after the NTS lesion, we observed a marked decrease in the density of NOS terminals in the ipsilateral NA. After injection of PHA-L into the central NTS, a dense group of PHA-L fibres was seen in the rostral NA, principally ipsilaterally. Afferent fibres from the esophagus were found around the NOS cell bodies in the central NTS, and many of these NOS neurons were double labeled with cholera toxin-gold after injection of this tracer into the NA. NOS terminals were found around NA neurons that were retrogradely labelled from the esophagus. We conclude that the NOS neurons in the central NTS act as interneurons in a central pathway connecting esophageal afferents and efferents.

Amino Acid Oxidoreductases↗
PubMed1995

Morphology and connections of neurons in area 17 projecting to the extrastriate areas MT and 19DM and to the superior colliculus in the monkey Callithrix jacchus.

Neurons of area 17, the primary visual cortex, project to various anatomically and physiologically different extrastriate areas and subcortical regions. In the present investigation, we addressed the question of whether the efferent neurons in area 17 can contribute to functional diversity between these regions. We approached this question by analyzing the dendritic morphology of neurons in area 17 projecting to area MT, area 19DM, and the superior colliculus in the new world simian primate Callithrix jacchus, because dendritic morphology is an important factor in determining physiological properties of nerve cells. Retrograde transport of fluorochromes injected into the target regions, and intracellular injections of Lucifer yellow in the prelabelled neurons, revealed the following. 1) Morphologically identical large pyramidal cells in layer VI of area 17 project to all three targets. Some of them possess axon collaterals to two or all three targets, suggesting that they provide common information to all three areas. 2) Pyramidal cells in layer IIIc projecting to area MT form a morphologically homogeneous population. 3) Three small to medium-sized pyramidal cell types in layers IIIa-c, spiny stellate cells in layer IIIc, and another large pyramidal cell type in layer VI project to area 19DM. 4) Pyramidal cells in the lower two-thirds of layer V in area 17 project to the superior colliculus. In conclusion, we have shown that in Callithrix one efferent pathway may originate from several cell types. However, with the exception of the large cells in layer VI, efferent cells projecting to area MT, area 19DM, and the superior colliculus were morphologically distinct. This suggests that functional differences between brain regions could arise in part from morphological heterogeneity between and within the efferent cell populations.

Animals↗
PubMed2005

Human brain activation during passive listening to sounds from different locations: an fMRI and MEG study.

Recent animal and human studies indicate the existence of a neural pathway for sound localization, which is similar to the "where" pathway of the visual system and distinct from the sound identification pathway. This study sought to highlight this pathway using a passive listening protocol. We employed fMRI to study cortical areas, activated during the processing of sounds coming from different locations, and MEG to disclose the temporal dynamics of these areas. In addition, the hypothesis of different activation levels in the right and in the left hemispheres, due to hemispheric specialization of the human brain, was investigated. The fMRI results indicate that the processing of sound, coming from different locations, activates a complex neuronal circuit, similar to the sound localization system described in monkeys known as the auditory "where" pathway. This system includes Heschl's gyrus, the superior temporal gyrus, the supramarginal gyrus, and the inferior and middle frontal lobe. The MEG analysis allowed assessment of the timing of this circuit: the activation of Heschl's gyrus was observed 139 ms after the auditory stimulus, the peak latency of the source located in the superior temporal gyrus was at 156 ms, and the inferior parietal lobule and the supramarginal gyrus peaked at 162 ms. Both hemispheres were found to be involved in the processing of sounds coming from different locations, but a stronger activation was observed in the right hemisphere.

Acoustic Stimulation↗
PubMed2003

Stimulation-induced reset of hippocampal theta in the freely performing rat.

Previous research has suggested that visual and auditory stimuli in a working memory task have the ability to reset hippocampal theta, perhaps allowing an organism to encode the incoming information optimally. The present study examined two possible neural pathways involved in theta resetting. Rats were trained on a visual discrimination task in an operant chamber. At the beginning of a trial, a light appeared over a centrally located lever that the rat was required to press to receive a water reward. There was a 30-s intertrial interval before the next light stimulus appeared. After learning the task, all rats received surgical implantation of stimulating electrodes in both the fornix and the perforant path and recording electrodes, bilaterally in the hippocampus. After surgery, theta was recorded before and after the light stimulus to determine whether resetting to the visual stimulus occurred. During the intertrial interval, rats received single-pulse electrical stimulation of either the fornix or perforant path. Theta was recorded both before and after the electrical stimulation to determine whether resetting occurred. In this experiment, hippocampal theta was reset after all three stimulus conditions (light, perforant path, and fornix stimulation), with the greatest degree of reset occurring after the fornix stimulation. The results suggest that activation of the perforant path and fornix may underlie theta reset and provide a mechanism by which the hippocampus may enhance cognitive processing.

Animals↗
PubMed2001

Acute stress and dexamethasone rapidly increase hippocampal somatostatin synthesis and release from the dentate gyrus hilus.

Somatostatin is a neuropeptide whose facilitatory action in the generation of long-term potentiation (LTP) in the hippocampal dentate gyrus has been associated with memory processes. Since stress and memory seem to share some neural pathways, we studied somatostatin release from dentate gyrus hilar cells of the hippocampus in unanesthetized free-moving rats subjected to stress or dexamethasone treatments. In parallel, the number of dentate gyrus hilar cells expressing somatostatin mRNA was quantified by nonradioactive in situ hybridization in these two experimental conditions. Rats were stereotaxically implanted with a push-pull cannula in the dentate gyrus hilar region. Animals were perfused 1 week later in basal or stress (30 min immobilization stress) conditions. The other group was intraperitoneally injected with the synthetic glucocorticoid dexamethasone (3 mg/kg b.w.). Samples were collected every 15 min for somatostatin radioimmunoassay. In parallel, in other groups of animals undergoing the same treatments, brains were removed for in situ hybridization studies with an oligonucleotide labeled with digoxigenin that recognizes somatostatin-14. The results showed that stress induced a significant increase in somatostatin release from dentate gyrus hilar cells 30-45 min after immobilization stress application. Dexamethasone-injected animals exhibited a similar response 45 min after drug administration. In situ hybridization analysis revealed that the two treatments significantly increased the number of cells expressing somatostatin mRNA in the hilar region. In conclusion, somatostatin interneurons of the hippocampal hilar region appear to be a novel stress stimulus target. Their rapid reactivity, expressed as modifications of both somatostatin release and number of cells expressing somatostatin mRNA, provides an interesting model of neuronal plasticity.

Acute Disease↗
PubMed1983

Two specific markers for neural differentiation of embryonal carcinoma cells.

Two multipotential embryonal carcinoma (EC) cell lines, 1003 and 1009, can be induced to form preferentially neural derivatives in vitro. Synthesis of specific proteins during neural differentiation was followed by two-dimensional gel electrophoresis. The comparison of protein patterns obtained with neural and non-neural derivatives of these EC cell lines indicates that two changes are specific for the neural pathway: (i) the appearance of a new beta-tubulin isoform and (ii) the accumulation of the brain isozyme of creatine phosphokinase already present in small amounts in EC stem cells. These changes were found to take place early in the course of differentiation and to occur even when neurite outgrowth was prevented.

Animals↗
PubMed1988

The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila.

In Drosophila, the very first steps in neurogenesis appear to be controlled by a small group of zygotically acting genes termed the neurogenic loci. Mutations in any of these genes result in a misrouting of epidermal lineages into the neural pathway. Morphological and molecular studies suggest that the correct ectodermal differentiation is mediated by a cell-cell interaction mechanism and that at least some of the neurogenic loci are involved in this mechanism. The molecular analyses of the neurogenic loci Notch and Delta revealed that the putative gene products are large transmembrane proteins with homology to mammalian epidermal growth factor. We describe here a molecular analysis of Enhancer of split [E(spl)], a third neurogenic locus, which displays striking genetic interactions with both Notch and Delta, suggesting a close functional relationship of the respective gene products. We provide evidence for a single genetic complementation group corresponding to a single transcription unit which is necessary for wild-type E(spl) function. P-element-mediated transformation indicates that this transcription unit includes functions associated with both the dominant E(spl)D mutation and the recessive visible allele groucho, and is necessary for the correct differentiation of the embryonic nervous system.

Animals↗
PubMed1996

Feeding induced by pharmacological blockade of fatty acid metabolism is selectively attenuated by hindbrain injections of the galanin receptor antagonist, M40.

Galanin has been shown to stimulate feeding when injected intracranially in rats. Lesion and Fos studies have shown that the neural pathway for feeding stimulated by mercaptoacetate (MA)-induced blockade of fatty acid oxidation includes several structures rich in galanin cell bodies or terminals. In the present experiment, we examined the role of hindbrain galanin in feeding stimulated by MA. We found that galanin (1 nmol) stimulates feeding when injected in the nucleus of the solitary tract (NTS), a site that is crucial for MA-induced feeding, or into the fourth ventricle (4V, 1 or 5 nmol) and that NTS or 4V injections of the galanin receptor antagonist, M40 (1.5 or 5 nmol), completely blocked feeding induced by MA (68 mg/kg). The effect of the M40 appeared to be specific for MA-induced feeding, since M40 did not significantly attenuate either feeding induced by the antimetabolic glucose analog, 2-deoxy-D-glucose (2DG, 100 or 200 mg/kg), or deprivation-induced water intake. Results suggest that feeding induced by decreased fatty acid oxidation relies upon galaninergic terminals in the hindbrain. Furthermore, results indicate that hindbrain neurons involved in MA-induced feeding differ neurochemically from those important for 2DG-induced feeding.

Animals↗
PubMed1992

Functional regeneration and recovery of locomotor activity in spinally transected lamprey.

Spinally transected lamprey recovery locomotor function within 3-6 weeks, and recovery is due, in part, to functional regeneration of neural pathways in the central nervous system (CNS). Our data demonstrate for the first time in the lamprey that descending axons arising from brainstem command neurons can functionally regenerate and restore locomotor initiation below a healed spinal transection site. Immediately after behavioral recovery (3-6 weeks) the locomotor pattern was incomplete but returned to normal during the remainder of the recovery period (6-40 weeks). Initially, the extent of regeneration of descending axons was limited but increased to at least 30-50 mm at recovery times of 24-40 weeks. Regenerated giant Muller axons do not contribute significantly to recovery of locomotor function; rather, regenerated axons of smaller reticulospinal neurons appear to restore locomotor initiation. The restoration of locomotor coordination across a spinal lesion is dependent on two mechanisms: regeneration of spinal coordinating neurons and mechanosensory inputs. Comparisons are made to spinal cord regeneration in other lower vertebrates and to the relative lack of CNS regeneration and behavioral recovery in higher vertebrates.

Animals↗
PubMed1992

Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells.

In the regenerating newt tail, epimorphic regeneration--which recapitulates morphologically normal embryonic development--proceeds along a rostrocaudal differentiation gradient. Innervation of the new myomeres results from the spinal roots of segments rostral to the amputation plane and from ventral roots emerging from the lateroventral region of the regenerating spinal cord, in which motor neurons are differentiating. Electron microscopy and an indirect immunofluorescence study with anti-glial fibrillary acid protein (GFAP) confirm that the ventrolateral part of the regenerated ependymal tube gives rise to cells of the ventral root sheath and the spinal ganglia. Anti-GFAP and anti-neurofilament antibodies showed that ependymoglial cells and Schwann cells may play a role in neuronal pathfinding by helping guide and stabilize pioneering axons as they extend toward the myomeres. The carbohydrate epitope NC-1 is expressed in the spinal cord, in sheath cells of the spinal ganglia and in the non-myelin-forming Schwann cells of the peripheral nervous system. L1, a Ca++ independent neural cell adhesion molecule, was detected in the axonal compartments of the regenerating spinal cord, on immature and/or non-myelin-forming Schwann cells within the peripheral nervous system (PNS), and on nerve fibers within the regenerate. These immunohistochemical observations collectively support the hypothesis that Schwann cells already present in the blastema could be involved in organizing neural pathways.

Animals↗