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The Kobe Journal of Medical Sciences Dec 2015Corticospinal tract (CST) neurons are dislocated in the motor cortex of Reelin-deficient mouse, reeler. In the present study, we examined whether postnatal axonal growth...
Corticospinal tract (CST) neurons are dislocated in the motor cortex of Reelin-deficient mouse, reeler. In the present study, we examined whether postnatal axonal growth arising from these dislocated CST neurons are normal or not with use of anterograde tracer, DiI and retrograde tracer, HRP. A single injection of DiI into the motor cortex of the normal and reeler mice was made during postnatal period and 8-24 hours later, the animals were sacrificed to examine DiI-labeled CST axons at the lower medulla and spinal cord. Both in the normal and reeler mice, CST axons arrived at the pyramidal decussation and entered into the contralateral spinal cord around on postnatal day (P) 0.5, and descend in the ventral area of the contralateral dorsal funiculus at C2 level on P2, at C8 level on P3, at the mid-thoracic level on P4, and at the upper lumbar level on P8. The similar results were also demonstrated by the retrograde labeling of CST neurons with injection of HRP into the C1 level or upper lumbar enlargement. Next, we examined CaMKIIα expression in the CST axons of the adult normal and reeler mice. CaMKIIα-immunopositive fibers were recognized throughout the CST pathway from the internal capsule to the dorsal funiculus of the spinal cord both in the normal and reeler mice. The present study has demonstrated that ectopic location of cell bodies of reeler CST neurons do not affect postnatal development of CST axons in the spinal cord.
Topics: Animals; Axons; Biomarkers; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cell Adhesion Molecules, Neuronal; Extracellular Matrix Proteins; Female; Male; Mice; Mice, Neurologic Mutants; Nerve Tissue Proteins; Pyramidal Tracts; Reelin Protein; Serine Endopeptidases
PubMed: 27323786
DOI: No ID Found -
Frontiers in Neural Circuits 2014Identification of neural networks and pathways involved in activation and modulation of spinal central pattern generators (CPGs) in the absence of the descending control... (Review)
Review
Identification of neural networks and pathways involved in activation and modulation of spinal central pattern generators (CPGs) in the absence of the descending control from the brain is important for further understanding of neural control of movement and for developing innovative therapeutic approaches to improve the mobility of spinal cord injury patients. Activation of the hindlimb innervating segments by sacrocaudal (SC) afferent input and by specific application of neurochemicals to the sacral networks is feasible in the isolated spinal cord preparation of the newborn rat. Here we review our recent studies of sacral relay neurons with lumbar projections and evaluate their role in linking the sacral and thoracolumbar (TL) networks during different motor behaviors. Our major findings show that: (1) heterogeneous groups of dorsal, intermediate and ventral sacral-neurons with ventral and lateral ascending funicular projections mediate the activation of the locomotor CPGs through sacral sensory input; and (2) rhythmic excitation of lumbar flexor motoneurons, produced by bath application of alpha-1 adrenoceptor agonists to the sacral segments is mediated exclusively by ventral clusters of sacral-neurons with lumbar projections through the ventral funiculus.
Topics: Animals; Central Pattern Generators; Locomotion; Lumbar Vertebrae; Neural Pathways; Neurons; Receptors, Adrenergic, alpha-1; Rodentia; Sacrum; Spinal Cord
PubMed: 25520624
DOI: 10.3389/fncir.2014.00143 -
Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons.Neuroscience Jan 2015Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance....
Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1-S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1-L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons.
Topics: Adrenergic Fibers; Animals; Axons; Bacterial Proteins; Choline O-Acetyltransferase; Female; Glucagon-Like Peptide-1 Receptor; Immunoenzyme Techniques; Interneurons; Luminescent Proteins; Male; Medulla Oblongata; Mice, Transgenic; Motor Neurons; Neuroanatomical Tract-Tracing Techniques; Nitric Oxide Synthase; Peritoneal Cavity; Posterior Horn Cells; Proglucagon; Sacrum; Stilbamidines; Thoracic Vertebrae
PubMed: 25450967
DOI: 10.1016/j.neuroscience.2014.10.043 -
Brain Research Mar 2015The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to...
The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion.
Topics: Animals; Biomechanical Phenomena; Cats; Decerebrate State; Electric Stimulation; Electromyography; Epidural Space; Locomotion; Lumbar Vertebrae; Muscle, Skeletal; Spinal Cord
PubMed: 25446455
DOI: 10.1016/j.brainres.2014.11.003 -
Frontiers in Neural Circuits 2014We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT)...
We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.
Topics: Action Potentials; Animals; Biophysics; Cats; Cerebellar Cortex; Electric Stimulation; Electroencephalography; Functional Laterality; Nerve Net; Neurons; Spinal Cord; Spinocerebellar Tracts
PubMed: 25386122
DOI: 10.3389/fncir.2014.00128 -
Journal of Toxicologic Pathology Jul 2014Oligodendroglioma is a rare tumor originating from oligodendrocytes found mainly in the cerebrum in aged rats. Only a few reports have shown spontaneous occurrence of...
Oligodendroglioma is a rare tumor originating from oligodendrocytes found mainly in the cerebrum in aged rats. Only a few reports have shown spontaneous occurrence of this tumor in the spinal cord, and no report has mentioned its occurrence in young rats. We encountered a case of spontaneous oligodendroglioma in the lumbar portion of the spinal cord in a young (9 weeks old) female BrlHan:WIST@Jcl (GALAS) rat. Here we report the detailed histopathological and immunohistochemical characteristics of this case. No clinical signs, no gross lesions at necropsy, and no specific changes in hematology or blood biochemistry were observed. The tumor was located in the dorsal funiculus in the lumbar portion of the spinal cord and widely spread to the dorsal root nerve. The neoplastic cells showed a sheet-like growth pattern and had small round nuclei, clear cytoplasm and distinct cell borders that resulted in a honeycomb pattern. No mitotic figures or other histological lesions were observed. The neoplastic cells were positively stained for Olig2 and PCNA. The present case was considered to be a low-grade oligodendroglioma based on the histological and immunohistochemical features. To our knowledge, our case is considered to be extremely rare and the first report in a young rat.
PubMed: 25352716
DOI: 10.1293/tox.2014-0010 -
Physiological Reports Sep 2014The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here,...
The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-tsDCS (c-tsDCS), but reduced during anodal-tsDCS (a-tsDCS). After-effects were dependent on the frequency of the test stimulation. c-tsDCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-tsDCS had opposite effects. During and after c-tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a-tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS-based interventions.
PubMed: 25263206
DOI: 10.14814/phy2.12157 -
Journal of Neurotrauma Feb 2015Deficits in bladder function are complications following spinal cord injury (SCI), severely affecting quality of life. Normal voiding function requires coordinated...
Deficits in bladder function are complications following spinal cord injury (SCI), severely affecting quality of life. Normal voiding function requires coordinated contraction of bladder and urethral sphincter muscles dependent upon intact lumbosacral reflex arcs and integration of descending and ascending spinal pathways. We previously reported, in electrophysiological recordings, that segmental reflex circuit neurons in anesthetized male rats were modulated by a bilateral spino-bulbo-spinal pathway in the mid-thoracic lateral funiculus. In the present study, behavioral measures of bladder voiding reflexes and hematuria (hemorrhagic cystitis) were obtained to assess the correlation of plasticity-dependent recovery to the degree of lateral funiculus sparing and mid-thoracic lesion level. Adult rats received mid-thoracic-level lesions at one of the following severities: complete spinal transection; bilateral dorsal column lesion; unilateral hemisection; bilateral dorsal hemisection; a bilateral lesion of the lateral funiculi and dorsal columns; or a severe contusion. Voiding function and hematuria were evaluated by determining whether the bladder was areflexic (requiring manual expression, i.e., "crede maneuver"), reflexive (voiding initiated by perineal stroking), or "automatic" (spontaneous voiding without caretaker assistance). Rats with one or both lateral funiculi spared (i.e., bilateral dorsal column lesion or unilateral hemisection) recovered significantly faster than animals with bilateral lateral funiculus lesions, severe contusion, or complete transection. Bladder reflex recovery time was significantly slower the closer a transection lesion was to T10, suggesting that proximity to the segmental sensory and sympathetic innervation of the upper urinary tract (kidney, ureter) should be avoided in the choice of lesion level for SCI studies of micturition pathways. In addition, hematuria duration was significantly longer in males, compared to females, despite similar bladder reflex onset times. We conclude that the sparing of the mid-thoracic lateral funiculus on one side is required for early recovery of bladder reflex voiding function and resolution of hematuria.
Topics: Animals; Disease Models, Animal; Female; Hematuria; Male; Rats; Rats, Wistar; Recovery of Function; Reflex; Spinal Cord Injuries; Urinary Bladder; Urination
PubMed: 25137571
DOI: 10.1089/neu.2013.3247 -
The International Journal of... 2014Much biological experimental data are represented as curves, including measurements of growth, hormone, or enzyme levels, and physical structures. Here we consider the...
Much biological experimental data are represented as curves, including measurements of growth, hormone, or enzyme levels, and physical structures. Here we consider the multiple testing problem of comparing two or more nonlinear curves. We model smooth curves of unknown form nonparametrically using penalized splines. We use random effects to model subject-specific deviations from the group-level curve. We present an approach that allows examination of overall differences between the curves of multiple groups and detection of sections in which the curves differ. Adjusted p-values for each single comparison can be obtained by exploiting the connection between semiparametric mixed models and linear mixed models and employing an approach for multiple testing in general parametric models. In simulations, we show that the probability of false-positive findings of differences between any two curves in at least one position can be controlled by a pre-specified error level. We apply our method to compare curves describing the form of the mouse dorsal funiculus - a morphological curved structure in the spinal cord - in mice wild-type for the gene encoding EphA4 or heterozygous with one of two mutations in the gene.
Topics: Animals; Bayes Theorem; Computer Simulation; Genotype; Male; Mice; Models, Statistical; Mutation; Nonlinear Dynamics; Sensitivity and Specificity; Spinal Cord Diseases
PubMed: 24902010
DOI: 10.1515/ijb-2013-0003 -
Journal of Neuropathology and... Apr 2014We provide evidence of cortical neuronopathy in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis, an established model of...
We provide evidence of cortical neuronopathy in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis, an established model of chronic multiple sclerosis. To investigate phenotypic perturbations in neurons in this model, we used apoptotic markers and immunohistochemistry with antibodies to NeuN and other surrogate markers known to be expressed by adult pyramidal Layer V somas, including annexin V, encephalopsin, and Emx1. We found no consistent evidence of chronic loss of Layer V neurons but detected both reversible and chronic decreases in the expression of these markers in conjunction with evidence of cortical demyelination and presynaptic loss. These phenotypic perturbations were present in, but not restricted to, the neocortical Layer V. We also investigated inflammatory responses in the cortex and subcortical white matter of the corpus callosum and spinal dorsal funiculus and found that those in the cortex and corpus callosum were delayed compared with those in the spinal cord. Inflammatory infiltrates initially included T cells, neutrophils, and Iba1-positive microglia/macrophages in the corpus callosum, whereas only Iba1-positive cells were present in the cortex. These data indicate that we have identified a new temporal pattern of subtle phenotypic perturbations in neocortical neurons in this chronic multiple sclerosis model.
Topics: Animals; Caspase 3; Cell Death; Disease Models, Animal; Encephalitis; Freund's Adjuvant; Humans; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; Motor Neurons; Multiple Sclerosis; Myelin Basic Protein; Myelin-Oligodendrocyte Glycoprotein; Neocortex; Peptide Fragments; Phosphopyruvate Hydratase; Synaptophysin; Time Factors
PubMed: 24607968
DOI: 10.1097/NEN.0000000000000058