bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Distinct Subgroup of Small DRG Cells Express GDNF Receptor Components and GDNF Is Protective for These Neurons after Nerve Injury
Authors: Bennett David L. H. , Michael Gregory J. , Ramachandran Navin , Munson John B. , Averill Sharon , Yan Qiao , McMahon Stephen B. , Priestley John V. 
Published: April 2018

Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme thiamine monophosphatase (TMP). Here we show that these neurons express the receptor components for glial-derived neurotrophic factor (GDNF) signaling (RET, GFRα-1, and GFRα-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFRα-1, GFRα-2, or GFRα-1 plus GFRα-2.GDNF, but not nerve growth factor (NGF), can prevent several axotomy-induced changes in these neurons, including the downregulation of IB4 binding, TMP activity, and somatostatin expression. GDNF also prevents the slowing of conduction velocity that normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GDNF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophin treatment.
Morphine Administered in the Substantia Gelatinosa of the Spinal Trigeminal Nucleus Caudalis Inhibits Nociceptive Activities in the Spinal Trigeminal Nucleus Oralis
Authors: Dallel Radhouane , Dualé Christian , Molat Jean-Louis 
Published: April 2018

The present study investigates the effects of morphine microinjection into the spinal trigeminal nucleus caudalis (Sp5C) or the spinal trigeminal nucleus oralis (Sp5O) on C-fiber-evoked activities of Sp5O convergent neurons, after supramaximal percutaneous electrical stimulation in halothane-anesthetized rats.When it was microinjected into the Sp5O, morphine (2.5 μg in 0.25 μl) never depressed the C-fiber-evoked responses of Sp5O convergent neurons (n= 13), whereas these neurons were responsive to the inhibitory effects of systemic morphine (6 mg/kg, i.v.) in a naloxone-reversible manner. On the contrary, morphine microinjected into the Sp5C produced a naloxone-reversible inhibition of the C-fiber-evoked responses of Sp5O neurons (n= 14). The magnitude and the time course of this effect varied according to the location of the injection sites. After microinjection into the superficial laminae (n= 7), a strong depressive effect of morphine (7 ± 5% of control) on the C-fiber-evoked responses was apparent as soon as 5 min after the injection and could always be reversed by naloxone, administered either intravenously (0.4 mg/kg) or locally (2.5 μg in 0.6 μl) at the same site as morphine. After microinjection into deeper laminae (V–VI), a significant depressive effect (34 ± 5% of control) of morphine could be detected only 20 min after the injection and was reversed only by intravenous administration of naloxone.These results suggest that morphine exerts its antinociceptive action on Sp5O convergent neurons by blocking the C-fiber inputs that relay in the Sp5C substantia gelatinosa. The mechanisms that underlie the activation of Sp5O convergent neurons by C-fibers and the inhibition of C-fiber-evoked responses of Sp5O convergent neurons by morphine microinjected into the Sp5C are discussed.
Intersegmental Coordination of Limb Movements during Locomotion: Mathematical Models Predict Circuits That Drive Swimmeret Beating
Authors: Skinner Frances K. , Mulloney Brian 
Published: April 2018

Normal locomotion in arthropods and vertebrates is a complex behavior, and the neural mechanisms that coordinate their limbs during locomotion at different speeds are unknown. The neural modules that drive cyclic movements of swimmerets respond to changes in excitation by changing the period of the motor pattern. As period changes, however, both intersegmental phase differences and the relative durations of bursts of impulses in different sets of motor neurons are preserved. To investigate these phenomena, we constructed a cellular model of the local pattern-generating circuit that drives each swimmeret. We then constructed alternative intersegmental circuits that might coordinate these local circuits. The structures of both the model of the local circuit and the alternative models of the coordinating circuit were based on and constrained by previous experimental results on pattern-generating neurons and coordinating interneurons.To evaluate the relative merits of these alternatives, we compared their dynamics with the performance of the real circuit when the level of excitation was changed. Many of the alternative coordinating circuits failed. One coordinating circuit, however, did effectively match the performance of the real system as period changed from 1 to 3.2 Hz. With this coordinating circuit, both the intersegmental phase differences and the relative durations of activity within each of the local modules fell within the ranges characteristic of the normal motor pattern and did not change significantly as period changed. These results predict a mechanism of coordination and a pattern of intersegmental connections in the CNS that is amenable to experimental test.
Response Classes in the Dorsal Cochlear Nucleus and Its Output Tract in the Chloralose-Anesthetized Cat
Authors: Joris Philip X. 
Published: April 2018

Neurons in the dorsal cochlear nucleus (DCN) can be classified into three major physiological classes on the basis of responses to pure tone and broadband noise stimuli. A circuit diagram that associates these classes with different cell types has been proposed. According to this proposal, type II cells are inhibitory interneurons that respond well to tones and poorly to broadband noise, type IV cells are projection neurons with the opposite behavior, and type III cells are an inhomogeneous class with intermediate properties. To test the associations proposed, I compared the response type distribution in the DCN with its output tract, the dorsal acoustic stria (DAS), in chloralose-anesthetized cats.Axonal recordings in the DAS showed type III and IV responses as in DCN, but no type II responses. Compared with reports in decerebrate animals, fewer type IV neurons were encountered having sustained inhibition that generated strongly nonmonotonic responses to tones in both DCN and DAS. The presence of type II responses in the nucleus, but not in the output tract, offers strong support for the proposed association with DCN interneurons. On the other hand, the distinction between type III and IV responses needs refinement because the differences are only graded and because both types of responses occur in DAS, which shows that they are both associated with projection neurons.
rMAL Is a Glycosphingolipid-Associated Protein of Myelin and Apical Membranes of Epithelial Cells in Kidney and Stomach
Authors: Frank Marcus , van der Haar Marjan E. , Schaeren-Wiemers Nicole , Schwab Martin E. 
Published: April 2018

rMAL, the rat myelin and lymphocyte protein, is a small hydrophobic protein of 17 kDa with four putative transmembrane domains and is expressed in oligodendrocytes and Schwann cells, the myelinating cells of the nervous system. In addition, transcript expression has been found in kidney, spleen, and intestine. Confocal microscopy and immunoelectron microscopy with an affinity-purified antibody localized rMAL to compact myelin in a pattern similar to the structural myelin proteins: myelin basic protein and proteolipid protein. In kidney and stomach epithelia, rMAL is located almost exclusively on the apical (luminal) membranes of the cells lining distal tubuli in kidney and the glandular part of the stomach. Biochemical analysis of plasma membranes isolated from spinal cord and kidney demonstrated that rMAL is a proteolipid that is present in detergent insoluble complexes typical for proteins associated with glycosphingolipids. Lipid and protein analysis showed a co-enrichment of glycosphingolipids and rMAL protein within these complexes, indicating a close association of rMAL to glycosphingolipids in myelin and in kidneyin vivo.We conclude that specific rMAL-glycosphingolipid interactions may lead to the formation and maintenance of stable protein–lipid microdomains in myelin and apical epithelial membranes. They may contribute to specific properties of these highly specialized plasma membranes.
Response of Thalamocortical Neurons to Hypoxia: A Whole-Cell Patch-Clamp Study
Authors: Erdemli Gül , Crunelli Vincenzo 
Published: April 2018

The effect of hypoxia (3–4 min of 95% N2, 5% CO2) on thalamocortical (TC) neurons was investigated using the whole-cell patch-clamp technique in rat dorsal lateral geniculate nucleus slices kept submerged at 32°C. The predominant feature of the response of TC neurons to hypoxia was an increase in input conductance (ΔGN= 117 ± 15%,n= 33) that was accompanied by an inward shift in baseline holding current (IBH) at −65 and −57 mV (ΔIBH= −45 ± 6 pA,n= 18, and −25 ± 8 pA,n= 33, respectively) but not at −40 mV. The hypoxia-induced increase inGN(as well as the shift inIBH) was abolished by procedures that are known to blockIh, i.e., bath application of 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (100–300 μm) (ΔGN= 5 ± 13%,n= 11) and CsCl (2–3 mm) (ΔGN= 16 ± 16%,n= 5), or low [Na+]o(ΔGN= 10 ± 10%,n= 5), whereas bath application of BaCl2(0.1–2.0 mm) had no significant effect (ΔGN= 128 ± 14%,n= 8). The hypoxic response was also abolished in low [Ca+2]o(ΔGN= 25 ± 16%, ΔIBH= −6 ± 8 pA,n= 13), but was unaffected by recording with electrodes containing EGTA (10 mm), BAPTA (10–30 mm), Cs+, or Cl−, as well as in the presence of external tetraethylammonium and 4-aminopyridine. Furthermore, preincubation of the slices with botulinum toxin A (100 nm), which is known to reduce Ca2+-dependent transmitter release, blocked the hypoxic response (ΔGN= −3 ± 15%, ΔIBH= 10 ± 5 pA,n= 4).We suggest that a positive shift in the voltage-dependence ofIhand a change in its activation kinetics, which transforms it into a fast activating current, may be responsible for the hypoxia-induced changes inGNandIBH, probably via an increase in Ca+2-dependent transmitter release.
Identification of the Dopamine D3 Receptor in Oligodendrocyte Precursors: Potential Role in Regulating Differentiation and Myelin Formation
Authors: Bongarzone Ernesto R. , Howard Sherrel G. , Schonmann Vilma , Campagnoni Anthony T. 
Published: April 2018

Expression of the dopamine D3 receptor (D3r) was found in primary mixed glial cultures from newborn brain and in the corpus callosumin vivoduring the peak of myelination. Expression of the D3r mRNA, but not D2r mRNA, was detected as early as 5 din vitro(DIV) by RT-PCR. Immunoblot studies revealed D3r protein was also expressed in the cultures. Double immunofluorescence analysis for the D3r and for surface markers of specific stages of oligodendrocyte development indicated that D3r expression occurred in precursors and in immature oligodendrocytes but not in mature oligodendrocytes (i.e., A2B5+007−01−and A2B5+007+01−cells but not A2B5−007+01+cells). Confocal microscopic analysis indicated that D3r was associated with cell bodies and cell membranes but not with the processes emanating from cell somas. Immunohistochemistry of brain sections revealed the presence of D3r in some oligodendrocytes located mainly within the genu and radiato of the corpus callosum during the active period of myelination.Treatment of cultures with 20 μmquinpirole led to decreased numbers of O1+oligodendrocytes possessing myelin-like membranes as well as an increase in the number of precursors in 14 DIV cultures. This effect was prevented by the dopamine antagonist haloperidol. These results show that the D3r expression is not restricted to neurons but it is also expressed in differentiating oligodendrocytes before terminal maturation. It also suggests that dopamine or some other D3r ligand may play a role in oligodendrocyte differentiation and/or the formation of myelin by mature oligodendrocytes.
Mediodorsal Thalamus Plays a Critical Role in the Development of Limbic Motor Seizures
Authors: Cassidy Robert M. , Gale Karen 
Published: April 2018

Limbic motor seizures in animals, analogous to complex partial seizures in humans, result in a consistent activation of the mediodorsal thalamus (MD) and, with prolonged seizures, damage to MD. This study examined the functional role of MD in focally evoked limbic motor seizures in the rat. GABA- and glutamate (Glu)-mediated synaptic transmissions in MD were evaluated for an influence on seizures evoked from area tempestas (AT), a discrete epileptogenic site in the rostral piriform cortex.A GABAAreceptor agonist, Glu receptor antagonists, or a GABA-elevating agent were focally microinfused into MD before evoking seizures by focal application of bicuculline methiodide into the ipsilateral AT. Focal pretreatment of MD with the GABAAagonist muscimol (190 pmol) protected against seizures evoked from AT. Seizure protection was also obtained with the focal application of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (500 pmol), an antagonist of the AMPA subtype of Glu receptors, into MD. In contrast, focal pretreatment of MD with a competitive antagonist of the NMDA receptor 2-amino-7-phosphonoheptanoic acid (500 pmol) did not attenuate seizures. The anticonvulsant effects achieved with intra-MD injections of muscimol and NBQX were site-specific, because no seizure protection was obtained with injections placed 2 mm ventral or lateral to MD. Prolonged seizure protection was obtained following GABA elevation in MD after the application of the GABA transaminase inhibitor vigabatrin (194 nmol). These results suggest the following: (1) MD is a critical participant in the generation of seizures elicited focally from piriform cortex; (2) transmission via AMPA receptors, but not NMDA receptors, in MD regulates limbic seizure propagation; and (3) a GABA-mediated system exists within MD, the enhancement of which protects against focally evoked limbic motor seizures.
Partial Inactivation of the Primary Motor Cortex Hand Area: Effects on Individuated Finger Movements
Authors: Schieber Marc H. , Poliakov Andrew V. 
Published: April 2018

After large lesions of the primary motor cortex (M1), voluntary movements of affected body parts are weak and slow. In addition, the relative independence of moving one body part without others is lost; attempts at individuated movements of a given body part are accompanied by excessive, unintended motion of contiguous body parts. The effects of partial inactivation of the M1 hand area are comparatively unknown, however. If the M1 hand area contains the somatotopically ordered finger representations implied by the classic homunculus or simiusculus, then partial inactivation might produce weakness, slowness, and loss of independence of one or two adjacent digits without affecting other digits. But if control of each finger movement is distributed in the M1 hand area as many studies suggest, then partial inactivation might produce dissociation of weakness, slowness, and relative independence of movement, and which fingers movements are impaired might be unrelated to the location of the inactivation along the central sulcus.To investigate the motoric deficits resulting from partial inactivation of the M1 hand area, we therefore made single intracortical injections of muscimol as trained monkeys performed visually cued, individuated flexion–extension movements of the fingers and wrist. We found little if any evidence that which finger movements were impaired after each injection was related to the injection location along the central sulcus. Unimpaired fingers could be flanked on both sides by impaired fingers, and the flexion movements of a given finger could be unaffected even though the extension movements were impaired, or vice versa. Partial inactivation also could produce dissociated weakness and slowness versus loss of independence in a given finger movement. These findings suggest that control of each individuated finger movement is distributed widely in the M1 hand area.
Schwann Cells Proliferate at Rat Neuromuscular Junctions during Development and Regeneration
Authors: Love Flora M. , Thompson Wesley J. 
Published: April 2018

Terminal Schwann cells (TSCs) cover neuromuscular junctions and are important in the repair and maintenance of these synapses. We have examined how these cells are generated at developing junctions and how their number is regulated during repair of nerve injury. At birth, approximately half of the junctions in rat soleus and extensor digitorum longus muscles have one TSC soma. Somata are absent from the remainder, although Schwann cell (SC) processes arising from somata along the preterminal axon cover almost all of these synapses. By 2 months of age, junctions have gained an additional two to three TSCs. Most of this gain occurs during the first 2 postnatal weeks and largely precedes the expansion of endplate size. Although the initial addition is caused by cell migration, mitotic labeling shows extensive division of TSCs at junctions. A slower addition of TSCs occurs in adult muscles, and TSC number in the adult is correlated with endplate size.During repair of nerve injury, TSC number is regulated by a combination of signals from motor neurons and denervated tissue. As shown previously (Connor et al., 1987), denervation of adult muscles did not, in itself, cause TSC mitosis. However, TSCs became mitotic during reinnervation. Partial denervation induced division of TSCs at innervated but not denervated endplates. A disproportionate number of these mitotic cells were found at endplates contacted by TSC processes extended from nearby denervated endplates, contacts known to promote nerve sprouting. These results show an association between TSC mitotic activity and alterations in synaptic structure during development, sprouting, and reinnervation.
Perinatal Gonadectomy Exerts Regionally Selective, Lateralized Effects on the Density of Axons Immunoreactive for Tyrosine Hydroxylase in the Cerebral Cortex of Adult Male Rats
Authors: Kritzer M. F. 
Published: April 2018

The catecholamine innervation of the cerebral cortex is essential for its normal operations and is implicated in cortical dysfunction in mental illness. Previous studies in rats have shown that the maturational tempo of these afferents is highly responsive to changes in gonadal hormones. The present findings show that perinatal hormone manipulation also has striking, region- and hemisphere-specific consequences for cortical catecholamines in adulthood.The effect of perinatal gonadectomy on catecholamines was examined in representative sensory, motor, and association cortices of adult male rats by combining hormone manipulation with immunocytochemistry for tyrosine hydroxylase, a rate-limiting enzyme in catecholamine biosynthesis. Qualitative and quantitative comparison of immunoreactivity in rats perinatally gonadectomized or sham-operated revealed complex changes in gonadectomized subjects; in cingulate cortex, TH immunoreactivity was strongly and bilaterally diminished, in sensory and motor cortices, axon density was decreased in left hemispheres, but was minimally affected on the right, and in a premotor cortex, gonadectomy was without significant effect in either hemisphere. Corresponding analyses in gonadectomized rats supplemented with testosterone revealed a protective influence, albeit one in which TH immunoreactivity so showed regional and hemispheric variability in responsiveness to hormone replacement. These complex patterns of TH sensitivity suggest highly asymmetric hormone stimulation of cortical catecholamines. Such discriminative action may contribute to sex differences in the functional maturation and lateralization of the cortex and may also have bearing on disorders such as dyslexia, which show sexual dimorphisms, and in which functional laterality of the cortex may be particularly at issue.
Neural Changes after Operant Conditioning of the Aerial Respiratory Behavior inLymnaea stagnalis
Authors: Spencer Gaynor E. , Syed Naweed I. , Lukowiak Ken 
Published: April 2018

In this study, we demonstrate neural changes that occurred during operant conditioning of the aerial respiratory behavior ofLymnaea stagnalis. Aerial respiration inLymnaeaoccurs at the water interface and is achieved by opening and closing movements of its respiratory orifice, the pneumostome. This behavior is controlled by a central pattern generator (CPG), the neurons of which, as well as the motoneurons innervating the pneumostome, have previously been identified and their synaptic connections well characterized.The respiratory behavior was operantly conditioned by applying a mechanical stimulus to the open pneumostome whenever the animal attempted to breathe. This negative reinforcement to the open pneumostome resulted in its immediate closure and a significant reduction in the overall respiratory activity. Electrophysiological recordings from the isolated CNSs after operant conditioning showed that the spontaneous patterned respiratory activity of the CPG neurons was significantly reduced. This included reduced spontaneous activity of the CPG interneuron involved in pneumostome opening (input 3 interneuron) and a reduced frequency of spontaneous tonic activity of the CPG interneuron [right pedal dorsal 1 (RPeD1)]. The ability to trigger the patterned respiratory activity by electrical stimulation of RPeD1 was also significantly reduced after operant conditioning. This study therefore demonstrates significant changes within a CPG that are associated with changes in a rhythmic homeostatic behavior after operant conditioning.
Upregulation of Tumor Necrosis Factor α Transport across the Blood–Brain Barrier after Acute Compressive Spinal Cord Injury
Authors: Pan Weihong , Kastin Abba J. , Bell Richard L. , Olson Richard D. 
Published: April 2018

Tumor necrosis factor α (TNF) is a cytokine that is involved in the inflammatory process after CNS injury and is implicated in neuroregeneration. A saturable transport system for TNF located at the blood–brain barrier (BBB) is responsible for the limited entry of TNF from blood to the CNS in normal mice.After partial disruption of the BBB by compression of the lumbar spinal cord, permeability to TNF was increased not only in the lumbar spinal cord but also in brain and distal spinal cord segments, where the BBB remained intact. The increase in the entry of TNF to the CNS followed a biphasic temporal pattern, with a first peak immediately after injury and a second peak starting on day 3; these changes lasted longer than the mere disruption of the BBB. The increased entry of TNF was abolished by addition of excess unlabeled TNF, showing that the transport system for TNF remained saturable after spinal cord injury (SCI) and providing evidence that the enhanced entry of TNF could not be explained by diffusion or leakage.This study adds strong support for our concept that the saturable transport system for TNF across the BBB can be upregulated in the diseased state, and it suggests that the BBB is actively involved in the modulation of the processes of degeneration and regeneration after SCI.