Anatomic variation of the abducens nerve in a single cadaver dissection: the "petrobasilar canal".

PubMed

Pizzolorusso, Felice; Cirotti, Andrea; Pizzolorusso, Gianfranco

2017-04-01

Anatomic variations of the petrosphenoid ligament, Dorello's canal and the course of the abducens nerve have been extensively described over the past years. In the present report of a single cadaver dissection, we describe an unusual course of the abducens nerve at the level of the petrous bone. The right abducens nerve did not enter Dorello's canal, but ran below the petrous bone through a narrow canal in the petrobasilar suture, which we called the "petrobasilar canal". No anatomic variations of the left abducens nerve were noted.

A case of isolated abducens nerve paralysis in maxillofacial trauma

PubMed Central

Keskin, Elif Seda; Keskin, Ekrem; Atik, Bekir; Koçer, Abdülkadir

2015-01-01

Nervus abducens is a pure motor nerve located in the pons. It retracts the eyeball laterally by stimulating rectus lateralis muscle. In case of their paralysis, diplopia and restriction in the eye movements while looking sideways, are seen. Since the same signs are seen due to the muscle entrapment in blowout fractures, its differential diagnosis has importance in terms of the treatment protocol and avoiding unnecessary operations. In this article, we present a 22-year-old male patient who was referred to our department due to the prediagnosis of blowout fracture following maxillofacial trauma. However, he was diagnosed with abducens nerve paralysis after the consultations and analysis and his restriction of movement was resolved via systemic steroid treatment instead of unnecessary operation. PMID:26981484

Precraniate origin of cranial motoneurons

PubMed Central

Dufour, Héloïse D.; Chettouh, Zoubida; Deyts, Carole; de Rosa, Renaud; Goridis, Christo; Joly, Jean-Stéphane; Brunet, Jean-François

2006-01-01

The craniate head is innervated by cranial sensory and motor neurons. Cranial sensory neurons stem from the neurogenic placodes and neural crest and are seen as evolutionary innovations crucial in fulfilling the feeding and respiratory needs of the craniate “new head.” In contrast, cranial motoneurons that are located in the hindbrain and motorize the head have an unclear phylogenetic status. Here we show that these motoneurons are in fact homologous to the motoneurons of the sessile postmetamorphic form of ascidians. The motoneurons of adult Ciona intestinalis, located in the cerebral ganglion and innervating muscles associated with the huge “branchial basket,” express the transcription factors CiPhox2 and CiTbx20, whose vertebrate orthologues collectively define cranial motoneurons of the branchiovisceral class. Moreover, Ciona's postmetamorphic motoneurons arise from a hindbrain set aside during larval life and defined as such by its position (caudal to the prosensephalic sensory vesicle) and coexpression of CiPhox2 and CiHox1, whose orthologues collectively mark the vertebrate hindbrain. These data unveil that the postmetamorphic ascidian brain, assumed to be a derived feature, in fact corresponds to the vertebrate hindbrain and push back the evolutionary origin of cranial nerves to before the origin of craniates. PMID:16735475

Abducens Nerve in Patients with Type 3 Duane’s Retraction Syndrome

PubMed Central

Hwang, Jeong-Min

2016-01-01

Background We have previously reported that the presence of the abducens nerve was variable in patients with type 3 Duane’s retraction syndrome (DRS), being present in 2 of 5 eyes (40%) and absent in 3 (60%) on magnetic resonance imaging (MRI). The previous study included only 5 eyes with unilateral DRS type 3. Objectives To supplement existing scarce pathologic information by evaluating the presence of the abducens nerve using high resolution thin-section MRI system in a larger number of patients with DRS type 3, thus to provide further insight into the pathogenesis of DRS. Data Extraction A retrospective review of medical records on ophthalmologic examination and high resolution thin-section MRI at the brainstem level and orbit was performed. A total of 31 patients who showed the typical signs of DRS type 3, including abduction and adduction deficit, globe retraction, narrowing of fissure on adduction and upshoot and/or downshoot, were included. The abducens nerve and any other extraocular muscle abnormalities discovered by MRI were noted. Results DRS was unilateral in 26 patients (84%) and bilateral in 5 patients (16%). Two out of 5 bilateral patients had DRS type 3 in the right eye and DRS type 1 in the left eye. Of the 34 affected orbits with DRS type 3 in 31 patients, the abducens nerve was absent or hypoplastic in 31 eyes (91%) and present in 3 eyes (9%). Patients with a present abducens nerve showed more limitation in adduction compared to patients with an absent abducens nerve (P = 0.030). Conclusions The abducens nerve is absent or hypoplastic in 91% of DRS type 3. Patients with a present abducens nerve showed more prominent limitation of adduction. As DRS type 3 partly share the same pathophysiology with type 1 and 2 DRS, the classification of DRS may have to be revised according to MRI findings. PMID:27352171

Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

PubMed Central

Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

2010-01-01

After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

Motoneuron excitability of the quadriceps decreases during a fatiguing submaximal isometric contraction.

PubMed

Finn, Harrison T; Rouffet, David M; Kennedy, David S; Green, Simon; Taylor, Janet L

2018-04-01

During fatiguing voluntary contractions, the excitability of motoneurons innervating arm muscles decreases. However, the behavior of motoneurons innervating quadriceps muscles is unclear. Findings may be inconsistent because descending cortical input influences motoneuron excitability and confounds measures during exercise. To overcome this limitation, we examined effects of fatigue on quadriceps motoneuron excitability tested during brief pauses in descending cortical drive after transcranial magnetic stimulation (TMS). Participants ( n = 14) performed brief (~5-s) isometric knee extension contractions before and after a 10-min sustained contraction at ~25% maximal electromyogram (EMG) of vastus medialis (VM) on one ( n = 5) or two ( n = 9) days. Electrical stimulation over thoracic spine elicited thoracic motor evoked potentials (TMEP) in quadriceps muscles during ongoing voluntary drive and 100 ms into the silent period following TMS (TMS-TMEP). Femoral nerve stimulation elicited maximal M-waves (M max ). On the 2 days, either large (~50% M max ) or small (~15% M max ) TMS-TMEPs were elicited. During the 10-min contraction, VM EMG was maintained ( P = 0.39), whereas force decreased by 52% (SD 13%) ( P < 0.001). TMEP area remained unchanged ( P = 0.9), whereas large TMS-TMEPs decreased by 49% (SD 28%) ( P = 0.001) and small TMS-TMEPs by 71% (SD 22%) ( P < 0.001). This decline was greater for small TMS-TMEPs ( P = 0.019; n = 9). Therefore, without the influence of descending drive, quadriceps TMS-TMEPs decreased during fatigue. The greater reduction for smaller responses, which tested motoneurons that were most active during the contraction, suggests a mechanism related to repetitive activity contributes to reduced quadriceps motoneuron excitability during fatigue. By contrast, the unchanged TMEP suggests that ongoing drive compensates for altered motoneuron excitability. NEW & NOTEWORTHY We provide evidence that the excitability of quadriceps

Adaptability of the oxidative capacity of motoneurons

NASA Technical Reports Server (NTRS)

Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

1992-01-01

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

PubMed

Cho, Bum-Joo; Kim, Ji-Soo; Hwang, Jeong-Min

2013-12-01

A 55-year-old woman presented with diplopia following painful skin eruptions on the right upper extremity. On presentation, she was found to have 35 prism diopters of esotropia and an abduction limitation in the left eye. Two weeks later, she developed blepharoptosis and anisocoria with a smaller pupil in the right eye, which increased in the darkness. Cerebrospinal fluid analysis showed pleocytosis and a positive result for immunoglobulin G antibody to varicella zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome and contralateral abducens nerve palsy. After intravenous antiviral and steroid treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's syndrome and diplopia resolved after six months. Here we present the first report of Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

Natural history of idiopathic abducens nerve paresis in a young adult.

PubMed

Hussaindeen, Jameel Rizwana; Mani, Revathy; Rakshit, Archayeeta; Ramasubramanian, Srikanth; Vittal Praveen, Smitha

2016-01-01

The natural history of idiopathic abducens nerve paresis and the role of conservative management such as vision training during the recovery process is not well documented in the literature to the best of our knowledge. This case report presents the natural recovery process of idiopathic abducens nerve paresis in a young adult and the role of vision therapy in the recovery process. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Monkey extensor digitorum communis motoneuron pool: Proximal dendritic trees and small motoneurons.

PubMed

Jenny, Arthur B; Cheney, Paul D; Jenny, Andrew K

2018-05-14

Transverse sections of the monkey cervical spinal cord from a previous study (Jenny and Inukai, 1983) were reanalyzed using Neurolucida to create a three-dimensional display of extensor digitorum communis (EDC) motoneurons and proximal dendrites that had been labeled with horse radish peroxidase (HRP). The EDC motoneuron pool was located primarily in the C8 and T1 segments of the spinal cord. Small motoneurons (cell body areas less than 500 μm 2 and presumed to be gamma motoneurons) comprised about ten percent of the motoneurons and were located throughout the length of the motoneuron pool. Most small motoneurons were oblong in shape and had one or two major dendrites originating from the cell body in the transverse plane of section. The majority of the HRP labeled dendritic trees were directed either superiorly, dorsal-medially to the mid zone area between the base of the dorsal horn and the upper portion of the ventral horn, or medially to the ventromedial gray matter. The longer HRP labeled dendrites usually continued in the same radial direction as when originating from the cell body. As such we considered the radial direction of the longer proximal HRP labeled dendrites to be a reasonable estimate of the radial direction of the more distal dendritic tree. Our data suggest that the motoneuron dendritic tree as seen in transverse section has direction-oriented dendrites that extend toward functional terminal regions. Copyright © 2018 Elsevier B.V. All rights reserved.

Post-traumatic Unilateral Avulsion of the Abducens Nerve with Damage to Cranial Nerves VII and VIII: Case Report.

PubMed

Yamasaki, Fumiyuki; Akiyama, Yuji; Tsumura, Ryu; Kolakshyapati, Manish; Adhikari, Rupendra Bahadur; Takayasu, Takeshi; Nosaka, Ryo; Kurisu, Kaoru

2016-07-01

Traumatic injuries of the abducens nerve as a consequence of facial and/or head trauma occur with or without associated cervical or skull base fracture. This is the first report on unilateral avulsion of the abducens nerve in a 29-year-old man with severe right facial trauma. In addition, he exhibited mild left facial palsy, and moderate left hearing disturbance. Magnetic resonance imaging (MRI) using fast imaging employing steady-state acquisition (FIESTA) revealed avulsion of left sixth cranial nerve. We recommend thin-slice MR examination in patients with abducens palsy after severe facial and/or head trauma.

Mechanisms contributing to the dopamine induction of crawl-like bursting in leech motoneurons.

PubMed

Crisp, Kevin M; Gallagher, Brian R; Mesce, Karen A

2012-09-01

Dopamine (DA) activates fictive crawling behavior in the medicinal leech. To identify the cellular mechanisms underlying this activation at the level of crawl-specific motoneuronal bursting, we targeted potential cAMP-dependent events that are often activated through DA(1)-like receptor signaling pathways. We found that isolated ganglia produced crawl-like motoneuron bursting after bath application of phosphodiesterase inhibitors (PDIs) that upregulated cAMP. This bursting persisted in salines in which calcium ions were replaced with equimolar cobalt or nickel, but was blocked by riluzole, an inhibitor of a persistent sodium current. PDI-induced bursting contained a number of patterned elements that were statistically similar to those observed during DA-induced fictive crawling, except that one motoneuron (CV) exhibited bursting during the contraction rather than the elongation phase of crawling. Although DA and the PDIs produced similar bursting profiles, intracellular recordings from motoneurons revealed differences in altered membrane properties. For example, DA lowered motoneuron excitability whereas the PDIs increased resting discharge rates. We suggest that PDIs (and DA) activate a sodium-influx-dependent timing mechanism capable of setting the crawl rhythm and that multiple DA receptor subtypes are involved in shaping and modulating the phase relationships and membrane properties of cell-specific members of the crawl network to generate crawling.

Detailed anatomy of the abducens nerve in the lateral rectus muscle.

PubMed

Nam, Yong Seok; Kim, In-Beom; Shin, Sun Young

2017-10-01

The aims of this study were to elucidate the detailed anatomy of the abducens nerve in the lateral rectus muscle (LRM) and the intramuscular innervation pattern using Sihler staining. In this cohort study, 32 eyes of 16 cadavers were assessed. Dissection was performed from the LRM origin to its insertion. The following distances were measured: from LRM insertion to the bifurcation point of the abducens nerve, from LRM insertion to the entry site of the superior branch or inferior branch, from the upper border of the LRM to the entry site of the superior branch, from the lower border of LRM to the entry site of inferior branch, and the widths of the main trunk and superior and inferior branches. The single trunk of the abducens nerve divided into two branches 37 mm from insertion of the LRM, and 22 of 32 (68.8%) orbits showed only two superior and inferior branches with no subdivision. The superior branch entered the LRM more anteriorly (P = 0.037) and the superior branch was thinner than the inferior branch (P = 0.040). The most distally located intramuscular nerve ending was observed at 52.9 ± 3.5% of the length of each muscle. Non-overlap between the superior and inferior intramuscular arborization of the nerve was detected in 27 of 32 cases (84.4%). Five cases (15.6%) showed definite overlap of the superior and inferior zones. This study revealed the detailed anatomy of the abducens nerve in the LRM and provides helpful information to understand abducens nerve palsy. Clin. Anat. 30:873-877, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Intramuscular Distribution of the Abducens Nerve in the Lateral Rectus Muscle for the Management of Strabismus.

PubMed

Shin, Hyun Jin; Lee, Shin-Hyo; Shin, Kang-Jae; Koh, Ki-Seok; Song, Wu-Chul

2018-06-01

To elucidate the intramuscular distribution and branching patterns of the abducens nerve in the lateral rectus (LR) muscle so as to provide anatomical confirmation of the presence of compartmentalization, including for use in clinical applications such as botulinum toxin injections. Thirty whole-mount human cadaver specimens were dissected and then Sihler's stain was applied. The basic dimensions of the LR and its intramuscular nerve distribution were investigated. The distances from the muscle insertion to the point at which the abducens nerve enters the LR and to the terminal nerve plexus were also measured. The LR was 46.0 mm long. The abducens nerve enters the muscle on the posterior one-third of the LR and then typically divides into a few branches (average of 1.8). This supports a segregated abducens nerve selectively innervating compartments of the LR. The intramuscular nerve distribution showed a Y-shaped ramification with root-like arborization. The intramuscular nerve course finished around the middle of the LR (24.8 mm posterior to the insertion point) to form the terminal nerve plexus. This region should be considered the optimal target site for botulinum toxin injections. We have also identified the presence of an overlapping zone and communicating nerve branches between the neighboring LR compartments. Sihler's staining is a useful technique for visualizing the entire nerve network of the LR. Improving the knowledge of the nerve distribution patterns is important not only for researchers but also clinicians to understand the functions of the LR and the diverse pathophysiology of strabismus.

Paralytic squint due to abducens nerve palsy : a rare consequence of dengue fever

PubMed Central

2012-01-01

Background Dengue fever is an endemic illness in the tropics with early and post infectious complications affecting multiple systems. Though neurological sequelae including mononeuropathy, encephalopathy, transverse myelitis, polyradiculopathy, Guillain-Barre syndrome , optic neuropathy and oculomotor neuropathy have been reported in medical literature, the abducens nerve despite its notoriety in cranial neuropathies in a multitude of condition due to its long intracranial course had not been to date reported to manifest with lateral rectus paralysis following dengue. Case presentation A previously well 29 year old male with serologically confirmed dengue hemorrhagic fever developed symptomatic right lateral rectus palsy during the critical phase of the illness, which persisted into convalescence and post convalescence with proven deficit on Hess screen. Alternate etiologies were excluded by imaging, serology and electrophysiology. Conclusions The authors detail the first reported case of abducens nerve palsy complicating dengue fever in a previously healthy male from Sri Lanka. In a tropical country with endemic dengue infections, dengue related abducens neuropathy may be considered as a differential diagnosis in cases of acquired lateral rectus palsy after dengue fever. PMID:22799448

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

PubMed

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

[Electromyographic differential diagnosis in cases of abducens nerve paresis with nuclear or distal neurogenic sive myogenic origine (author's transl)].

PubMed

Heuser, M

1979-09-01

Abducens nerve paresis may be of nuclear, of peripheral distal neurogenic origine, or is simulated by a myogenic weakness of abduction. Polygraphic emg analysis of the oculoauricularphenomenon (oap) permits a differentiation. In the emg, the oap proved to be a physiologic and constant automatic and always bilateral interaction between the hemolateral abducens nerve and both Nn. faciales with corresponding and obligatory coinnervation of the Mm. retroauricularis of the external ear. In case of medullary, nuclear or internuclear lesions, the oap is disturbed, instable, diminished or abolished, whereas in distal neurogenic or myogenic paresis, even in complete paralysis the oap is bilaterally well preserved.

Unilateral abducens and bilateral facial nerve palsies associated with posterior fossa exploration surgery.

PubMed

Khalil, Ayman; Clerkin, James; Mandiwanza, Tafadzwa; Green, Sandra; Javadpour, Mohsen

2016-03-06

Multiple cranial nerves palsies following a posterior fossa exploration confined to an extradural compartment is a rare clinical presentation. This case report describes a young man who developed a unilateral abducens and bilateral facial nerve palsies following a posterior fossa exploration confined to an extradural compartment. There are different theories to explain this presentation, but the exact mechanism remains unclear. We propose that this patient cranial nerve palsies developed following cerebrospinal fluid (CSF) leak, potentially as a consequence of rapid change in CSF dynamics. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Unilateral abducens and bilateral facial nerve palsies associated with posterior fossa exploration surgery

PubMed Central

Khalil, Ayman; Clerkin, James; Mandiwanza, Tafadzwa; Green, Sandra; Javadpour, Mohsen

2016-01-01

Multiple cranial nerves palsies following a posterior fossa exploration confined to an extradural compartment is a rare clinical presentation. This case report describes a young man who developed a unilateral abducens and bilateral facial nerve palsies following a posterior fossa exploration confined to an extradural compartment. There are different theories to explain this presentation, but the exact mechanism remains unclear. We propose that this patient cranial nerve palsies developed following cerebrospinal fluid (CSF) leak, potentially as a consequence of rapid change in CSF dynamics. PMID:26951144

Muscle length-dependent contribution of motoneuron Cav1.3 channels to force production in model slow motor unit.

PubMed

Kim, Hojeong

2017-07-01

Persistent inward current (PIC)-generating Ca v 1.3 channels in spinal motoneuron dendrites are thought to be actively recruited during normal behaviors. However, whether and how the activation of PIC channels influences force output of motor unit remains elusive. Here, building a physiologically realistic model of slow motor unit I demonstrated that force production induced by the PIC activation is much smaller for short than lengthened muscles during the regular firing of the motoneuron that transitions from the quiescent state by either a brief current pulse at the soma or a brief synaptic excitation at the dendrites. By contrast, the PIC-induced force potentiation was maximal for short muscles when the motoneuron switched from a stable low-frequency firing state to a stable high-frequency firing state by the current pulse at the soma. Under the synaptic excitation at the dendrites, however, the force could not be potentiated by the transitioning of the motoneuron from a low- to a high-frequency firing state due to the simultaneous onset of PIC at the dendrites and firing at the soma. The strong dependency of the input-output relationship of the motor unit on the neuromodulation and Ia afferent inputs for the PIC channels was further shown under static variations in muscle length. Taken together, these findings suggest that the PIC activation in the motoneuron dendrites may differentially affect the force production of the motor unit, depending not only on the firing state history of the motoneuron and the variation in muscle length but also on the mode of motor activity. NEW & NOTEWORTHY Ca v 1.3 channels in motoneuron dendrites are actively involved during normal motor activities. To investigate the effects of the activation of motoneuron Ca v 1.3 channels on force production, a model motor unit was built based on best-available data. The simulation results suggest that force potentiation induced by Ca v 1.3 channel activation is strongly modulated not only by

Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis

PubMed Central

Granato, Michael

2016-01-01

During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator. PMID:27855159

Saccular and utricular inputs to sternocleidomastoid motoneurons of decerebrate cats.

PubMed

Kushiro, K; Zakir, M; Ogawa, Y; Sato, H; Uchino, Y

1999-06-01

Connections from the otolithic organs to sternocleidomastoid (SCM) motoneurons were studied in 20 decerebrate cats. The electrical stimulation was selective for the saccular or the utricular nerves. Postsynaptic potentials were recorded from antidromically identified SCM motoneurons; these muscles participate mainly in neck rotation and flexion. Partial transections of the brainstem at the level of the obex were performed to identify the possible pathway from the otolithic organs to the SCM motoneurons. Saccular or utricular nerve stimulation mainly evoked inhibitory postsynaptic potentials (IPSPs) in the ipsilateral SCM motoneurons. Some of the sacculus-induced IPSPs were preceded by small-amplitude excitatory PSPs (EPSPs). The latencies of the PSPs ranged from 1.8 to 3.1 ms after saccular nerve stimulation and from 1.7 to 2.8 ms after utricular nerve stimulation, indicating that most of the ipsilateral connections were disynaptic. In the contralateral SCM motoneurons, saccular nerve stimulation had no or faint effects, whereas utricular nerve stimulation evoked EPSPs in about two-thirds of neurons, and no visible PSPs in about one-third of neurons. The latencies of the EPSPs ranged from 1.5 to 2.0 ms, indicating the disynaptic connection. Thus, the results suggest a difference between the two otolithic innervating patterns of SCM motoneurons. After transection of the medial vestibulospinal tract (MVST), saccular nerve stimulation did not evoke IPSPs at all in ipsilateral SCM motoneurons, but some (11/40) neurons showed small-amplitude EPSPs. Most (24/33) of the utricular-activated IPSPs disappeared after transection, whereas the other 9 neurons still indicated IPSPs. In the contralateral SCM motoneurons, no utricular-activated EPSPs were recorded after transection. These MVST transection results suggest that most of the otolith-SCM pathways are located in the MVST at the obex level. However, the results also suggest the possibility that other otolith-SCM pathways

The effects of aging on hypoglossal motoneurons in rats.

PubMed

Schwarz, Emilie C; Thompson, Jodi M; Connor, Nadine P; Behan, Mary

2009-03-01

Aging can result in a loss of neuronal cell bodies and a decrease in neuronal size in some regions of the brain and spinal cord. Motoneuron loss in the spinal cord is thought to contribute to the progressive decline in muscle mass and strength that occurs with age (sarcopenia). Swallowing disorders represent a large clinical problem in elderly persons; however, age-related alterations in cranial motoneurons that innervate muscles involved in swallowing have been understudied. We aimed to determine if age-related alterations occurred in the hypoglossal nucleus in the brainstem. If present, these changes might help explain alterations at the neuromuscular junction and changes in the contractile properties of tongue muscle that have been reported in older rats. We hypothesized that with increasing age there would be a loss of motoneurons and a reduction in neuronal size and the number of primary dendrites associated with each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized with the neuronal marker NeuN in young (9-10 months), middle-aged (24-25 months), and old (32-33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde-labeled with injections of Cholera Toxin beta into the genioglossus muscle of the tongue and visualized using immunocytochemistry. Results indicated that the number of primary dendrites of hypoglossal motoneurons decreased significantly with age, while no age-associated changes were found in the number or size of hypoglossal motoneurons. Loss of primary dendrites could reduce the number of synaptic inputs and thereby impair function.

The Effects of Aging on Hypoglossal Motoneurons in Rats

PubMed Central

Schwarz, Emilie C.; Thompson, Jodi M.; Connor, Nadine P.; Behan, Mary

2008-01-01

Aging can result in a loss of neuronal cell bodies and a decrease in neuronal size in some regions of the brain and spinal cord. Motoneuron loss in the spinal cord is thought to contribute to the progressive decline in muscle mass and strength that occurs with age (sarcopenia). Swallowing disorders represent a large clinical problem in elderly persons; however, age-related alterations in cranial motoneurons that innervate muscles involved in swallowing have been understudied. We aimed to determine if age-related alterations occurred in the hypoglossal nucleus in the brainstem. If present, these changes might help explain alterations at the neuromuscular junction and changes in the contractile properties of tongue muscle that have been reported in older rats. We hypothesized that with increasing age, there would be a loss of motoneurons and a reduction in neuronal size and the number of primary dendrites associated with each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized with the neuronal marker NeuN in young (9–10 months), middle-aged (24–25 months), and old (32–33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde labeled with injections of Cholera Toxin β into the genioglossus muscle of the tongue and visualized using immunocytochemistry. Results indicated that the number of primary dendrites of hypoglossal motoneurons decreased significantly with age, while no age-associated changes were found in the number or size of hypoglossal motoneurons. Loss of primary dendrites could reduce the number of synaptic inputs and thereby impair function. PMID:18716837

MHC class I, beta2 microglobulin, and the INF-gamma receptor are upregulated in aged motoneurons.

PubMed

Edström, Erik; Kullberg, Susanna; Ming, Yu; Zheng, Huaiyu; Ulfhake, Brun

2004-12-15

During aging, spinal cord motoneurons show characteristic changes including the loss of afferent boutons, a selective process that associates with gliosis and behavioral motor impairment. Evidence suggests that the major histocompatibility complex Class I (MHC I) system may be involved in synaptic plasticity of neurons during development and regeneration. In search of a mechanism governing senescent changes in synaptic connectivity, we report evidence for increased expression of MHC I and beta2 microglobulin (beta2M) in motoneurons and glial-like profiles of 30-month-old rats. The regulatory signal(s) for MHC I expression in normal neurons remains unresolved but among tentative molecules are cytokines such as interferon-gamma (INF-gamma) and tumor necrosis factor alpha (TNF-alpha). Interestingly, aged motoneurons, overlapping with those showing increased levels of MHC I, contained increased levels of INF-gamma receptor message. INF-gamma mRNA was detected at low levels in most (8/9) of the aged spinal cords but only infrequently (2/9) in young adult spinal cords; however, the cellular localization of INF-gamma mRNA could not be determined. Our data also indicates that TNF-alpha is upregulated in the senescent spinal cord but that TNF-alpha immunoreactive protein does not associate with motoneurons. We report evidence for an increased expression of MHC I and beta2M in senescent spinal motoneurons and discuss the possibility that this regulation associates with INF-gamma or changes in neurotrophin signaling and neuron activity in senescence. (c) 2004 Wiley-Liss, Inc.

Inhibitory motoneurons in arthropod motor control: organisation, function, evolution.

PubMed

Wolf, Harald

2014-08-01

Miniaturisation of somatic cells in animals is limited, for reasons ranging from the accommodation of organelles to surface-to-volume ratio. Consequently, muscle and nerve cells vary in diameters by about two orders of magnitude, in animals covering 12 orders of magnitude in body mass. Small animals thus have to control their behaviour with few muscle fibres and neurons. Hexapod leg muscles, for instance, may consist of a single to a few 100 fibres, and they are controlled by one to, rarely, 19 motoneurons. A typical mammal has thousands of fibres per muscle supplied by hundreds of motoneurons for comparable behavioural performances. Arthopods--crustaceans, hexapods, spiders, and their kin--are on average much smaller than vertebrates, and they possess inhibitory motoneurons for a motor control strategy that allows a broad performance spectrum despite necessarily small cell numbers. This arthropod motor control strategy is reviewed from functional and evolutionary perspectives and its components are described with a focus on inhibitory motoneurons. Inhibitory motoneurons are particularly interesting for a number of reasons: evolutionary and phylogenetic comparison of functional specialisations, evolutionary and developmental origin and diversification, and muscle fibre recruitment strategies.

Usefulness of intraoperative electromyographic monitoring of oculomotor and abducens nerves during skull base surgery.

PubMed

Li, Zi-Yi; Li, Ming-Chu; Liang, Jian-Tao; Bao, Yu-Hai; Chen, Ge; Guo, Hong-Chuan; Ling, Feng

2017-10-01

Intraoperative neurophysiologic monitoring of the extraocular cranial nerve (EOCN) is not commonly performed because of technical difficulty and risk, reliability of the result and predictability of the postoperative function of the EOCN. We performed oculomotor nerve (CN III) and abducens nerve (CN VI) intraoperative monitoring in patients with skull base surgery by recording the spontaneous muscle activity (SMA) and compound muscle action potential (CMAP). Two types of needle electrodes of different length were percutaneously inserted into the extraocular muscles with the free-hand technique. We studied the relationships between the SMA and CMAP and postoperative function of CN III and CN VI. A total of 23 patients were included. Nineteen oculomotor nerves and 22 abducens nerves were monitored during surgery, respectively. Neurotonic discharge had a positive predictive value of less than 50% and negative predictive value of more than 80% for postoperative CN III and CN VI dysfunction. The latency of patients with postoperative CN III dysfunction was 2.79 ± 0.13 ms, longer than that with intact CN III function (1.73 ± 0.11 ms). One patient had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than that of intact CN VI function (2.11 ± 0.38 ms). There was no statistically significant difference between patients with paresis and with intact function. The method of intraoperative monitoring of EOCNs described here is safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems to have limited value in predicting the postoperative function of CN III and CN VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably relevant to postoperative CN III and CN VI dysfunction. However, a definite quantitative relationship has not been found between the amplitude and stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.

Electrical stimulation of transplanted motoneurons improves motor unit formation

PubMed Central

Liu, Yang; Grumbles, Robert M.

2014-01-01

Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

[Effect of abducens orthosis combined with walker on developmental dysplasia of the hip].

PubMed

Hu, Zhiyong; Xu, Yongqiang; Liang, Jieyu; Li, Kanghua; Liao, Qiande

2009-07-01

To evaluate the effect of abducens orthosis combined with walker on developmental dysplasia of the hip (DDH). A total of 126 patients (224 hips) with DDH aged 6-36 months in Xiangya Hospital was randomly divided into 2 groups: an orthosis combined with walker group and an improved hip frog cast fixation group. Seventy patients (130 hips) were treated by the orthosis combined with walker and 56 patients (94 hips) were treated by the improved hip frog cast fixation. We compared the effect and complications of the 2 groups. The fineness rates of the orthosis combined with walker group and the improved hip frog cast fixation group were 89.2% and 90.4%, respectively, with no significant difference (P>0.05). The rate of femoral head osteonecrosis in the orthosis combined with walker group was significantly lower than that in the improved hip frog cast fixation group (1.5% vs. 5.3%,P<0.05), but the re-dislocation rate in the former was significantly higher than that in the latter (6.9% vs. 1.1 %, P<0.05). Both methods are effective for DDH. Orthosis combined with walker has a lower proportion of femoral head osteonecrosis, but a higher proportion of re-dislocation.

HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

PubMed

Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

2017-11-29

Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43 , is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding

Functional Motor Recovery from Motoneuron Axotomy Is Compromised in Mice with Defective Corticospinal Projections

PubMed Central

Ding, Yuetong; Qu, Yibo; Feng, Jia; Wang, Meizhi; Han, Qi; So, Kwok-Fai; Wu, Wutian; Zhou, Libing

2014-01-01

Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI. PMID:25003601

Motoneurons secrete angiogenin to induce RNA cleavage in astroglia.

PubMed

Skorupa, Alexandra; King, Matthew A; Aparicio, Isabela M; Dussmann, Heiko; Coughlan, Karen; Breen, Bridget; Kieran, Dairin; Concannon, Caoimhin G; Marin, Philippe; Prehn, Jochen H M

2012-04-11

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin, encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that angiogenin administration shows promise as a neuroprotective therapeutic in studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism of action and target cells in the spinal cord, however, are largely unknown. Using mixed motoneuron cultures, motoneuron-like NSC34 cells, and primary astroglia cultures as model systems, we here demonstrate that angiogenin is a neuronally secreted factor that is endocytosed by astroglia and mediates neuroprotection in paracrine. We show that wild-type angiogenin acts unidirectionally to induce RNA cleavage in astroglia, while the ALS-associated K40I mutant is also secreted and endocytosed, but fails to induce RNA cleavage. Angiogenin uptake into astroglia requires heparan sulfate proteoglycans, and engages clathrin-mediated endocytosis. We show that this uptake mechanism exists for mouse and human angiogenin, and delivers a functional RNase output. Moreover, we identify syndecan 4 as the angiogenin receptor mediating the selective uptake of angiogenin into astroglia. Our data provide new insights into the paracrine activities of angiogenin in the nervous system, and further highlight the critical role of non-neuronal cells in the pathogenesis of ALS.

Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

NASA Technical Reports Server (NTRS)

Ishihara, A.; Roy, R. R.; Edgerton, V. R.

1995-01-01

The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

PubMed

Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

2017-06-01

Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

Postoperative full abduction in a patient of Duane retraction syndrome without an abducens nerve: a case report.

PubMed

Kim, Jae Hyoung; Hwang, Jeong-Min

2017-05-19

Duane retraction syndrome (DRS) consists of abduction deficit, globe retraction and upshoots or downshoots with adduction. The abducens nerve on the affected side is absent in type 1 DRS. After bilateral medial rectus muscle recession in unilateral type 1 DRS may improve the abduction limitation, but still more than -3 limitation remains. A 6-month-old boy presented with esotropia which had been noticed in early infancy. He showed limited abduction, fissure narrowing on attempted adduction and a small upshoot OS. Left abducens nerve was not identified on magnetic resonance imaging compatible with Duane retraction syndrome type 1. He showed full abduction after bilateral medial rectus recession of 6.0 mm at the age of 9 months, and remained orthotropia with full abduction OU 2 years postoperatively. He is my only patient with Duane retraction syndrome who showed full abduction after bilateral medial rectus recession. A patient with the type 1 Duane retraction syndrome rarely may show full abduction after bilateral medial rectus recession mimicking infantile esotropia.

Spike threshold dynamics in spinal motoneurons during scratching and swimming.

PubMed

Grigonis, Ramunas; Alaburda, Aidas

2017-09-01

Action potential threshold can vary depending on firing history and synaptic inputs. We used an ex vivo carapace-spinal cord preparation from adult turtles to study spike threshold dynamics in motoneurons during two distinct types of functional motor behaviour - fictive scratching and fictive swimming. The threshold potential depolarizes by about 10 mV within each burst of spikes generated during scratch and swim network activity and recovers between bursts to a slightly depolarized level. Slow synaptic integration resulting in a wave of membrane potential depolarization is the factor influencing the threshold potential within firing bursts during motor behaviours. Depolarization of the threshold potential decreases the excitability of motoneurons and may provide a mechanism for stabilization of the response of a motoneuron to intense synaptic inputs to maintain the motor commands within an optimal range for muscle activation. During functional spinal neural network activity motoneurons receive intense synaptic input, and this could modulate the threshold for action potential generation, providing the ability to dynamically adjust the excitability and recruitment order for functional needs. In the present study we investigated the dynamics of action potential threshold during motor network activity. Intracellular recordings from spinal motoneurons in an ex vivo carapace-spinal cord preparation from adult turtles were performed during two distinct types of motor behaviour - fictive scratching and fictive swimming. We found that the threshold of the first spike in episodes of scratching and swimming was the lowest. The threshold potential depolarizes by about 10 mV within each burst of spikes generated during scratch and swim network activity and recovers between bursts to a slightly depolarized level. Depolarization of the threshold potential results in decreased excitability of motoneurons. Synaptic inputs do not modulate the threshold of the first action

Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

SciTech Connect

Zhang, Yun; Wang, Jing; Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191

2011-01-14

Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increasedmore » motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.« less

Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

PubMed Central

Mantilla, Carlos B.; Bailey, Jeffrey P.; Zhan, Wen-Zhi; Sieck, Gary C.

2012-01-01

Following cervical spinal cord injury at C2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10 μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability. PMID:22227062

Direct connection of the nucleus reticularis gigantocellularis neurons with neck motoneurons in cats.

PubMed

Sasaki, S

1999-10-01

Functional connections of single reticulospinal neurons (RSNs) in the nucleus reticularis gigantocellularis (NRG) with ipsilateral dorsal neck motoneurons were examined with the spike-triggered averaging technique. Extracellular spikes of single NRG-RSNs activated antidromically from the C6, but not from the L1 segment (C-RSNs) were used as the trigger. These neurons were monosynaptically activated from the superior colliculus and the cerebral peduncle. Single-RSN PSPs were recorded in 43 dorsal neck motoneurons [biventer cervicis and complexus (BCC) and splenius (SPL)] for 21 NRG-RSNs and 135 motoneurons tested. All synaptic potentials were EPSPs, and most of their latencies, measured from the triggering spikes, were 0.8-1.5 ms, which is in a monosynaptic range. The amplitudes of single-RSN EPSPs were 10-360 microV. Spike-triggered averaging revealed single-RSN EPSPs in multiple motoneurons of the same species (SPL or BCC), their locations extending up to nearly 1 mm rostrocaudally. Synaptic connections of single RSNs with both SPL and BCC motoneurons were also found with some predominance for one of them. The results provide direct evidence that NRG-RSNs make monosynaptic excitatory connections with SPL and BCC motoneurons. It appears that some NRG-RSNs connect predominantly with SPL motoneurons and others with BCC motoneurons.

Enrichment of spinal cord cell cultures with motoneurons

PubMed Central

1978-01-01

Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

Accumulation of glycogen in axotomized adult rat facial motoneurons.

PubMed

Takezawa, Yosuke; Baba, Otto; Kohsaka, Shinichi; Nakajima, Kazuyuki

2015-06-01

This study biochemically determined glycogen content in the axotomized facial nucleus of adult rats up to 35 days postinsult. The amounts of glycogen in the transected facial nucleus were significantly increased at 5 days postinsult, peaked at 7 days postinsult, and declined to the control levels at 21-35 days postinsult. Immunohistochemical analysis with antiglycogen antibody revealed that the quantity of glycogen granules in the axotomized facial nucleus was greater than that in the control nucleus at 7 days postinjury. Dual staining methods with antiglycogen antibody and a motoneuron marker clarified that the glycogen was localized mainly in motoneurons. Immunoblotting and quantification analysis revealed that the ratio of inactive glycogen synthase (GS) to total GS was significantly decreased in the injured nucleus at about 1-3 days postinsult and significantly increased from 7 to 14 days postinsult, suggesting that glycogen is actively synthesized in the early period postinjury but suppressed after 7 days postinsult. The enhanced glycogen at about 5-7 days postinsult is suggested to be responsible for the decrease in inactive GS levels, and the decrease of glycogen after 7 days postinsult is considered to be caused by increased inactive GS levels and possibly the increase in active glycogen phosphorylase. © 2015 Wiley Periodicals, Inc.

Function of identified motoneurones and co-ordination of primary and secondary motor systems during zebra fish swimming.

PubMed Central

Liu, D W; Westerfield, M

1988-01-01

1. The activity of the two classes of motoneurones, primary and secondary, which innervate myotomal muscle fibres in the zebra fish, was monitored with electromyographic and intracellular techniques. 2. Simultaneous EMG and intracellular recordings from muscle fibres showed that the activity of the two motor systems and of individual primary motoneurones can be distinguished by recording EMG spikes during swimming. 3. Measurements of EMG spikes demonstrated that primary and secondary motoneurones are co-ordinately activated over a wide range of conditions during normal swimming. 4. During swimming the primary motoneurones within a given segment are usually co-activated although they sometimes fire independently. 5. When different primary motoneurones within a given segment are co-activated, they fire nearly synchronously. 6. We conclude that the primary motoneurones are used principally, although not exclusively, during fast swimming, struggling and the startle response, whereas secondary motoneurones function primarily during slower swimming. PMID:3253426

The alpha-motoneuron pool as transmitter of rhythmicities in cortical motor drive.

PubMed

Stegeman, Dick F; van de Ven, Wendy J M; van Elswijk, Gijs A; Oostenveld, Robert; Kleine, Bert U

2010-10-01

Investigate the effectiveness and frequency dependence of central drive transmission via the alpha-motoneuron pool to the muscle. We describe a model for the simulation of alpha-motoneuron firing and the EMG signal as response to central drive input. The transfer in the frequency domain is investigated. Coherence between stochastical central input and EMG is also evaluated. The transmission of central rhythmicities to the EMG signal relates to the spectral content of the latter. Coherence between central input to the alpha-motoneuron pool and the EMG signal is significant whereby the coupling strength hardly depends on the frequency in a range from 1 to 100 Hz. Common central input to pairs of alpha-motoneurons strongly increases the coherence levels. The often-used rectification of the EMG signal introduces a clear frequency dependence. Oscillatory phenomena are strongly transmitted via the alpha-motoneuron pool. The motoneuron firing frequencies do play a role in the transmission gain, but do not influence the coherence levels. Rectification of the EMG signal enhances the transmission gain, but lowers coherence and introduces a strong frequency dependency. We think that it should be avoided. Our findings show that rhythmicities are translated into alpha-motoneuron activity without strong non-linearities. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Synaptic control of the shape of the motoneuron pool input-output function

PubMed Central

Heckman, Charles J.

2017-01-01

Although motoneurons have often been considered to be fairly linear transducers of synaptic input, recent evidence suggests that strong persistent inward currents (PICs) in motoneurons allow neuromodulatory and inhibitory synaptic inputs to induce large nonlinearities in the relation between the level of excitatory input and motor output. To try to estimate the possible extent of this nonlinearity, we developed a pool of model motoneurons designed to replicate the characteristics of motoneuron input-output properties measured in medial gastrocnemius motoneurons in the decerebrate cat with voltage-clamp and current-clamp techniques. We drove the model pool with a range of synaptic inputs consisting of various mixtures of excitation, inhibition, and neuromodulation. We then looked at the relation between excitatory drive and total pool output. Our results revealed that the PICs not only enhance gain but also induce a strong nonlinearity in the relation between the average firing rate of the motoneuron pool and the level of excitatory input. The relation between the total simulated force output and input was somewhat more linear because of higher force outputs in later-recruited units. We also found that the nonlinearity can be increased by increasing neuromodulatory input and/or balanced inhibitory input and minimized by a reciprocal, push-pull pattern of inhibition. We consider the possibility that a flexible input-output function may allow motor output to be tuned to match the widely varying demands of the normal motor repertoire. NEW & NOTEWORTHY Motoneuron activity is generally considered to reflect the level of excitatory drive. However, the activation of voltage-dependent intrinsic conductances can distort the relation between excitatory drive and the total output of a pool of motoneurons. Using a pool of realistic motoneuron models, we show that pool output can be a highly nonlinear function of synaptic input but linearity can be achieved through adjusting the

Resistance of extraocular motoneuron terminals to effects of amyotrophic lateral sclerosis sera

NASA Technical Reports Server (NTRS)

Mosier, D. R.; Siklos, L.; Appel, S. H.

2000-01-01

In sporadic ALS (s-ALS), axon terminals contain increased intracellular calcium. Passively transferred sera from patients with s-ALS increase intracellular calcium in spinal motoneuron terminals in vivo and enhance spontaneous transmitter release, a calcium-dependent process. In this study, passive transfer of s-ALS sera increased spontaneous release from spinal but not extraocular motoneuron terminals, suggesting that the resistance to physiologic abnormalities induced by s-ALS sera in mice parallels the resistance of extraocular motoneurons to dysfunction and degeneration in ALS.

RNA content in spinal cord motoneurons during hypokinesia

NASA Technical Reports Server (NTRS)

Gorbunova, A. V.

1980-01-01

The effect of a diminished motor activity of rats upon the ribonucleic and (RNA) content in a single isolated motoneuron of frontal of their spinal cord was studied. Within a 1 to 30 day exposure of rats to the hypokinetic conditions, RNA content was found to decrease on the 1st, 3rd, and 5th day and to return to the initial level by the 7th day. No changes in RNA content were observed during the subsequent stages of the xperiments. The volume of the nerve cells declined on the 3rd and 5th day, whereas RNA concentration reduced on the 1st, 3rd, 5th, and 30th day.

Adaptations of motoneuron properties to chronic compensatory muscle overload

PubMed Central

Hałuszka, A.; Mrówczyński, W.; Gardiner, P. F.; Celichowski, J.

2015-01-01

The aim of the study was to determine whether chronic muscle overload has measurable effect on electrophysiological properties of motoneurons (MNs), and whether duration of this overload influences intensity of adaptations. The compensatory overload was induced in the rat medial gastrocnemius (MG) by bilateral tenotomy of its synergists (lateral gastrocnemius, soleus, and plantaris); as a result, only the MG was able to evoke the foot plantar flexion. To assure regular activation of the MG muscle, rats were placed in wheel-equipped cages and subjected to a low-level treadmill exercise. The intracellular recordings from MG motoneurons were made after 5 or 12 wk of the overload, and in a control group of intact rats. Some of the passive and threshold membrane properties as well as rhythmic firing properties were considerably modified in fast-type MNs, while remaining unaltered in slow-type MNs. The significant changes included a shortening of the spike duration and the spike rise time, an increase of the afterhyperpolarization amplitude, an increase of the input resistance, a decrease of the rheobase, and a decrease of the minimum current necessary to evoke steady-state firing. The data suggest higher excitability of fast-type MNs innervating the overloaded muscle, and a shift towards electrophysiological properties of slow-type MNs. All of the adaptations could be observed after 5 wk of the compensatory overload with no further changes occurring after 12 wk. This indicates that the response to an increased level of chronic activation of MNs is relatively quick and stable. PMID:25695651

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

PubMed Central

Millecamps, Stéphanie; Nicolle, Delphine; Ceballos-Picot, Irène; Mallet, Jacques; Barkats, Martine

2001-01-01

Using adenoviruses encoding reporter genes as retrograde tracers, we assessed the capacity of motoneurons to take up and retrogradely transport adenoviral particles injected into the muscles of transgenic mice expressing the G93A human superoxide dismutase mutation, a model of amyotrophic lateral sclerosis. Surprisingly, transgene expression in the motoneurons was significantly higher in symptomatic mice than in control or presymptomatic mice. Using botulinum toxin to induce nerve sprouting at neuromuscular junctions, we showed that the unexpectedly high level of motoneurons retrograde transduction results, at least in part, from newly acquired uptake properties of the sprouts. These findings demonstrate the remarkable uptake properties of amyotrophic lateral sclerosis motoneurons in response to denervation and the rationale of using intramuscular injections of adenoviruses to overexpress therapeutic proteins in motor neuron diseases. PMID:11404466

Unexpected factors affecting the excitability of human motoneurones in voluntary and stimulated contractions

PubMed Central

Khan, Serajul I.; Taylor, Janet L.

2016-01-01

Key points The output of human motoneurone pools decreases with fatiguing exercise, but the mechanisms involved are uncertain. We explored depression of recurrent motoneurone discharges (F‐waves) after sustained maximal voluntary contractions (MVCs).MVC depressed the size and frequency of F‐waves in a hand muscle but a submaximal contraction (at 50% MVC) did not.Surprisingly, activation of the motoneurones antidromically by stimulation of the ulnar nerve (at 20 or 40 Hz) did not depress F‐wave area or persistence.Furthermore, a sustained (3 min) MVC of a hand muscle depressed F‐waves in its antagonist but not in a remote hand muscle.Our findings suggest that depression of F‐waves after voluntary contractions is not simply due to repetitive activation of the motoneurones but requires descending voluntary drive.  Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools. Abstract There are major spinal changes induced by repetitive activity and fatigue that could contribute to ‘central’ fatigue but the mechanisms involved are poorly understood in humans. Here we confirmed that the recurrent motoneuronal discharge (F‐wave) is reduced during relaxation immediately after a sustained maximal voluntary contraction (MVC) of an intrinsic hand muscle (abductor digiti minimi, ADM) and explored the relationship between motoneurone firing and the depression of F‐waves in three ways. First, the depression (in both F‐wave area and F‐wave persistence) was present after a 10 s MVC (initial decrease 36.4 ± 19.1%; mean ± SD) but not after a submaximal voluntary contraction at 50% maximum. Second, to evoke motoneurone discharge without volitional effort, 10 s tetanic contractions were produced by supramaximal ulnar nerve stimulation at the elbow at physiological frequencies of 25 and 40 Hz. Surprisingly, neither produced depression of F‐waves in ADM to test supramaximal stimulation of the ulnar nerve at the wrist

Unexpected factors affecting the excitability of human motoneurones in voluntary and stimulated contractions.

PubMed

Khan, Serajul I; Taylor, Janet L; Gandevia, Simon C

2016-05-15

The output of human motoneurone pools decreases with fatiguing exercise, but the mechanisms involved are uncertain. We explored depression of recurrent motoneurone discharges (F-waves) after sustained maximal voluntary contractions (MVCs). MVC depressed the size and frequency of F-waves in a hand muscle but a submaximal contraction (at 50% MVC) did not. Surprisingly, activation of the motoneurones antidromically by stimulation of the ulnar nerve (at 20 or 40 Hz) did not depress F-wave area or persistence. Furthermore, a sustained (3 min) MVC of a hand muscle depressed F-waves in its antagonist but not in a remote hand muscle. Our findings suggest that depression of F-waves after voluntary contractions is not simply due to repetitive activation of the motoneurones but requires descending voluntary drive.  Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools. There are major spinal changes induced by repetitive activity and fatigue that could contribute to 'central' fatigue but the mechanisms involved are poorly understood in humans. Here we confirmed that the recurrent motoneuronal discharge (F-wave) is reduced during relaxation immediately after a sustained maximal voluntary contraction (MVC) of an intrinsic hand muscle (abductor digiti minimi, ADM) and explored the relationship between motoneurone firing and the depression of F-waves in three ways. First, the depression (in both F-wave area and F-wave persistence) was present after a 10 s MVC (initial decrease 36.4 ± 19.1%; mean ± SD) but not after a submaximal voluntary contraction at 50% maximum. Second, to evoke motoneurone discharge without volitional effort, 10 s tetanic contractions were produced by supramaximal ulnar nerve stimulation at the elbow at physiological frequencies of 25 and 40 Hz. Surprisingly, neither produced depression of F-waves in ADM to test supramaximal stimulation of the ulnar nerve at the wrist. Finally, a sustained MVC (3 min) of the

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells

PubMed Central

Gonzalez Porras, Maria A.; Durfee, Paul N.; Gregory, Ashley M.; Sieck, Gary C.; Brinker, C. Jeffrey; Mantilla, Carlos B.

2017-01-01

Background Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. New method We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. Results CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24 h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Comparison with existing method(s) Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. Conclusions CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. PMID:27641118

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells.

PubMed

Gonzalez Porras, Maria A; Durfee, Paul N; Gregory, Ashley M; Sieck, Gary C; Brinker, C Jeffrey; Mantilla, Carlos B

2016-11-01

Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

NASA Technical Reports Server (NTRS)

Chalmers, G. R.; Edgerton, V. R.

1989-01-01

The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons

PubMed Central

Cui, Dapeng; Dougherty, Kimberly J.; Machacek, David W.; Sawchuk, Michael; Hochman, Shawn; Baro, Deborah J.

2009-01-01

Studies in the developing spinal cord suggest that different motoneuron (MN) cell types express very different genetic programs, but the degree to which adult programs differ is unknown. To compare genetic programs between adult MN columnar cell types, we used laser capture micro-dissection (LCM) and Affymetrix microarrays to create expression profiles for three columnar cell types: lateral and medial MNs from lumbar segments and sympathetic preganglionic motoneurons located in the thoracic intermediolateral nucleus. A comparison of the three expression profiles indicated that ~7% (813/11,552) of the genes showed significant differences in their expression levels. The largest differences were observed between sympathetic preganglionic MNs and the lateral motor column, with 6% (706/11,552) of the genes being differentially expressed. Significant differences in expression were observed for 1.8% (207/11,552) of the genes when comparing sympathetic preganglionic MNs with the medial motor column. Lateral and medial MNs showed the least divergence, with 1.3% (150/11,552) of the genes being differentially expressed. These data indicate that the amount of divergence in expression profiles between identified columnar MNs does not strictly correlate with divergence of function as defined by innervation patterns (somatic/muscle vs. autonomic/viscera). Classification of the differentially expressed genes with regard to function showed that they underpin all fundamental cell systems and processes, although most differentially expressed genes encode proteins involved in signal transduction. Mining the expression profiles to examine transcription factors essential for MN development suggested that many of the same transcription factors participatein combinatorial codes in embryonic and adult neurons, but patterns of expression change significantly. PMID:16317082

Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability

PubMed Central

Fritz, Elsa; Izaurieta, Pamela; Weiss, Alexandra; Mir, Franco R.; Rojas, Patricio; Gonzalez, David; Rojas, Fabiola; Brown, Robert H.; Madrid, Rodolfo

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1G93A) increases persistent sodium inward currents (PCNa), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine) and nonspecific (spermidine and riluzole) blockers of voltage-sensitive sodium (Nav) channels restored basal calcium transients and prevented motoneuron death induced by ACM-hSOD1G93A. These findings suggest that riluzole, the only FDA-approved drug with known benefits for ALS patients, acts by inhibiting hyperexcitability. Together, our data document that a critical element mediating the non-cell-autonomous toxicity of ACM-hSOD1G93A on motoneurons is increased excitability, an observation with direct implications for therapy of ALS. PMID:23486205

Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons.

PubMed

Herzog, E; Landry, M; Buhler, E; Bouali-Benazzouz, R; Legay, C; Henderson, C E; Nagy, F; Dreyfus, P; Giros, B; El Mestikawy, S

2004-10-01

Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report that VGLUT1 and VGLUT2, two subtypes of vesicular glutamate transporters, are expressed in rat spinal motoneurons. Both proteins are present in somato-dendritic compartments as well as in axon terminals in primary cultures of immunopurified motoneurons and sections of spinal cord from adult rat. However, VGLUT1 and VGLUT2 are not found at neuromuscular junctions of skeletal muscles. After intracellular injection of biocytin in motoneurons, VGLUT2 is observed in anterogradely labelled terminals contacting Renshaw inhibitory interneurons. These VGLUT2- and VGLUT1-positive terminals do not express VAChT, the vesicular acetylcholine transporter. Overall, our study establishes for the first time that (i) mammalian spinal motoneurons express vesicular glutamate transporters, (ii) these motoneurons have the potential to release glutamate (in addition to acetylcholine) at terminals contacting Renshaw cells, and finally (iii) the VGLUTs are not present at neuromuscular synapses of skeletal muscles.

A central mesencephalic reticular formation projection to medial rectus motoneurons supplying singly and multiply innervated extraocular muscle fibers.

PubMed

Bohlen, Martin O; Warren, Susan; May, Paul J

2017-06-01

We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal gaze changes. C-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. Here, we tested whether C-group motoneurons in Macaca fascicularis monkeys receive a direct cMRF input by injecting this portion of the reticular formation with anterograde tracers in combination with injection of retrograde tracer into the medial rectus muscle. The results indicate that the cMRF provides a dense, bilateral projection to the region of the medial rectus C-group motoneurons. Numerous close associations between labeled terminals and each multiply innervated fiber motoneuron were present. Within the oculomotor nucleus, a much sparser ipsilateral projection onto some of the A- and B- group medial rectus motoneurons that supply singly innervated fibers was observed. Ultrastructural analysis demonstrated a direct synaptic linkage between anterogradely labeled reticular terminals and retrogradely labeled medial rectus motoneurons in all three groups. These findings reinforce the notion that the cMRF is a critical hub for oculomotility by proving that it contains premotor neurons supplying horizontal extraocular muscle motoneurons. The differences between the cMRF input patterns for C-group versus A- and B-group motoneurons suggest the C-group motoneurons serve a different oculomotor role than the others. The similar patterns of cMRF input to C-group motoneurons and preganglionic Edinger-Westphal motoneurons suggest that medial rectus C-group motoneurons may play a role in accommodation-related vergence. © 2017 Wiley Periodicals, Inc.

Fatigue of muscles weakened by death of motoneurons.

PubMed

Thomas, Christine K; Zijdewind, Inge

2006-01-01

Weakness is a characteristic of muscles influenced by the postpolio syndrome (PPS), amyotrophic lateral sclerosis (ALS), and spinal cord injury (SCI). The strength deficits relate to changes in muscle use and to the chronic denervation that can follow the spinal motoneuron death common to these disorders. PPS, ALS, and SCI also involve variable amounts of supraspinal neuron death, the effects of which on muscle weakness remains unclear. Nevertheless, weakness of muscle itself defines the functional consequences of these disorders. A weaker muscle requires an individual to work that muscle at higher than usual intensities relative to its maximal capacity, inducing progressive fatigue and an increased sense of effort. Little evidence is available to suggest that the fatigue commonly experienced by individuals with these disorders relates to an increase in the intrinsic fatigability of the muscle fibers. The only exception is when SCI induces chronic muscle paralysis. To reduce long-term functional deficits in these disorders, studies must identify the signaling pathways that influence neuron survival and determine the factors that encourage and limit sprouting of motor axons. This may ensure that a greater proportion of the fibers in each muscle remain innervated and available for use.

Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

PubMed

Hayakawa, T; Takanaga, A; Maeda, S; Ito, H; Seki, M

2000-11-01

The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

Dependence of phrenic motoneurone output on the oscillatory component of arterial blood gas composition.

PubMed Central

Cross, B A; Grant, B J; Guz, A; Jones, P W; Semple, S J; Stidwill, R P

1979-01-01

1. The hypothesis that respiratory oscillations of arterial blood gas composition influence ventilation has been examined. 2. Phrenic motoneurone output recorded in the C5 root of the left phrenic nerve and the respiratory oscillations of arterial pH in the right common carotid artery were measured in vagotomized anaesthetized dogs which had been paralysed and artificially ventilated. 3. The effect of a change in tidal volume for one or two breaths on phrenic motoneurone output was measured with the inspiratory pump set at a constant frequency similar to, and in phase with, the animal's own respiratory frequency. A reduction of tidal volume to zero or an increase by 30% led to a corresponding change of mean carotid artery pH level. The changes of carotid artery pH resulted in a change of phrenic motoneurone output, predominantly of expiratory time (Te) but to a lesser extent of inspiratory time (T1) and also peak amplitude of 'integrated' phrenic motoneurone output (Phr). Denervation of the carotid bifurcation blocked this response. 4. The onset of movement of the inspiratory pump was triggered by the onset of phrenic motoneurone output. When a time delay was interposed between them, the phase relationship between respiratory oscillations of arterial pH and phrenic motoneurone output altered. The dominant effect was to alter Te; smaller and less consistent changes of Phr and T1 were observed. 5. When the inspiratory pump was maintained at a constant frequency but independent of and slightly different from the animal's own respiratory frequency (as judged by phrenic motoneurone output), the phase relationship between phrenic motoneurone output and the respiratory oscillations of pH changed breath by breath over a sequence of 100-200 breaths, without change of the mean level of arterial blood gas composition. Te varied by up to 30% about its mean value depending on the phase relationship. Ti and Phr were also dependent on the phase relationship but varied to a lesser

ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

PubMed

Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

2018-05-24

Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

SciTech Connect

Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletalmore » muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.« less

Neuregulin 1 Reduces Motoneuron Cell Death and Promotes Neurite Growth in an in Vitro Model of Motoneuron Degeneration

PubMed Central

Mòdol-Caballero, Guillem; Santos, Daniel; Navarro, Xavier; Herrando-Grabulosa, Mireia

2018-01-01

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with no effective treatment currently available. Although the mechanisms of motoneuron (MN) death are still unclear, glutamate excitotoxicity and neuroinflammatory reaction are two main features in the neurodegenerative process of ALS. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. Several recent evidences suggest that NRG1 and their ErbB receptors are involved in ALS. However, further knowledge is still needed to clarify the role of the NRG1-ErbB pathway on MN survival. In this study we used an in vitro model of spinal cord organotypic cultures (SCOCs) subject to chronic excitotoxicity caused by DL-threo-β-hydroxyaspartic acid (THA) to characterize the effect of NRG1 on MN survival. Our results show that addition of recombinant human NRG1 (rhNRG1) to the medium significantly increased MN survival through the activation of ErbB receptors which was ablated with lapatinib (LP), an ErbB inhibitor, and reduced microglial reactivity overcoming the excitotoxicity effects. rhNRG1 activated the pro-survival PI3K/AKT pathway and restored the autophagic flux in the spinal cord culture. Moreover, addition of rhNRG1 to the medium promoted motor and sensory neurite outgrowth. These findings indicate that increasing NRG1 at the spinal cord is an interesting approach for promoting MN protection and regeneration. PMID:29375317

Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process.

PubMed

Jahn, Patrick; Berg, Rune W; Hounsgaard, Jørn; Ditlevsen, Susanne

2011-11-01

Stochastic leaky integrate-and-fire models are popular due to their simplicity and statistical tractability. They have been widely applied to gain understanding of the underlying mechanisms for spike timing in neurons, and have served as building blocks for more elaborate models. Especially the Ornstein-Uhlenbeck process is popular to describe the stochastic fluctuations in the membrane potential of a neuron, but also other models like the square-root model or models with a non-linear drift are sometimes applied. Data that can be described by such models have to be stationary and thus, the simple models can only be applied over short time windows. However, experimental data show varying time constants, state dependent noise, a graded firing threshold and time-inhomogeneous input. In the present study we build a jump diffusion model that incorporates these features, and introduce a firing mechanism with a state dependent intensity. In addition, we suggest statistical methods to estimate all unknown quantities and apply these to analyze turtle motoneuron membrane potentials. Finally, simulated and real data are compared and discussed. We find that a square-root diffusion describes the data much better than an Ornstein-Uhlenbeck process with constant diffusion coefficient. Further, the membrane time constant decreases with increasing depolarization, as expected from the increase in synaptic conductance. The network activity, which the neuron is exposed to, can be reasonably estimated to be a threshold version of the nerve output from the network. Moreover, the spiking characteristics are well described by a Poisson spike train with an intensity depending exponentially on the membrane potential.

Specificity in monosynaptic and disynaptic bulbospinal connections to thoracic motoneurones in the rat

PubMed Central

de Almeida, Anoushka T R; Kirkwood, Peter A

2013-01-01

The respiratory activity in the intercostal nerves of the rat is unusual, in that motoneurones of both branches of the intercostal nerves, internal and external, are activated during expiration. Here, the pathways involved in that activation were investigated in anaesthetised and in decerebrate rats by cross-correlation and by intracellular spike-triggered averaging from expiratory bulbospinal neurones (EBSNs), with a view to revealing specific connections that could be used in studies of experimental spinal cord injury. Decerebrate preparations, which showed the strongest expiratory activity, were found to be the most suitable for these measurements. Cross-correlations in these preparations showed monosynaptic connections from 16/19 (84%) of EBSNs, but only to internal intercostal nerve motoneurones (24/37, 65% of EBSN/nerve pairs), whereas disynaptic connections were seen for external intercostal nerve motoneurones (4/19, 21% of EBSNs or 7/25, 28% of EBSN/nerve pairs). There was evidence for additional disynaptic connections to internal intercostal nerve motoneurones. Intracellular spike-triggered averaging revealed excitatory postsynaptic potentials, which confirmed these connections. This is believed to be the first report of single descending fibres that participate in two different pathways to two different groups of motoneurones. It is of interest compared with the cat, where only one group of motoneurones is activated during expiration and only one of the pathways has been detected. The specificity of the connections could be valuable in studies of plasticity in pathological situations, but care will be needed in studying connections in such situations, because their strength was found here to be relatively weak. PMID:23774278

Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate

PubMed Central

Stagg, Stephanie B.; Guardiola, Amaris R.; Crews, Stephen T.

2011-01-01

Dopaminergic neurons play important behavioral roles in locomotion, reward and aggression. The Drosophila H-cell is a dopaminergic neuron that resides at the midline of the ventral nerve cord. Both the H-cell and the glutamatergic H-cell sib are the asymmetric progeny of the MP3 midline precursor cell. H-cell sib cell fate is dependent on Notch signaling, whereas H-cell fate is Notch independent. Genetic analysis of genes that could potentially regulate H-cell fate revealed that the lethal of scute [l(1)sc], tailup and SoxNeuro transcription factor genes act together to control H-cell gene expression. The l(1)sc bHLH gene is required for all H-cell-specific gene transcription, whereas tailup acts in parallel to l(1)sc and controls genes involved in dopamine metabolism. SoxNeuro functions downstream of l(1)sc and controls expression of a peptide neurotransmitter receptor gene. The role of l(1)sc may be more widespread, as a l(1)sc mutant shows reductions in gene expression in non-midline dopaminergic neurons. In addition, l(1)sc mutant embryos possess defects in the formation of MP4-6 midline precursor and the median neuroblast stem cell, revealing a proneural role for l(1)sc in midline cells. The Notch-dependent progeny of MP4-6 are the mVUM motoneurons, and these cells also require l(1)sc for mVUM-specific gene expression. Thus, l(1)sc plays an important regulatory role in both neurogenesis and specifying dopaminergic neuron and motoneuron identities. PMID:21558367

The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones

PubMed Central

Saywell, S A; Anissimova, N P; Ford, T W; Meehan, C F; Kirkwood, P A

2007-01-01

The descending control of respiratory-related motoneurones in the thoracic spinal cord remains the subject of some debate. In this study, direct connections from expiratory bulbospinal neurones to identified motoneurones were investigated using spike-triggered averaging and the strengths of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5–T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 μV. The overall strength of the connection supports previous measurements made by cross-correlation, but is about 10 times stronger than that reported in the only previous similar survey to use spike-triggered averaging. Calculations are presented to suggest that this input alone is sufficient to account for all the expiratory depolarization seen in the recorded motoneurones. However, extra sources of input, or amplification of this one, are likely to be necessary to produce a useful motoneurone output. PMID:17204500

Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation.

PubMed

Usui, Noriyoshi; Watanabe, Keisuke; Ono, Katsuhiko; Tomita, Koichi; Tamamaki, Nobuaki; Ikenaka, Kazuhiro; Takebayashi, Hirohide

2012-03-01

Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

Phosphatidylinositol 3-kinase activity in murine motoneuron disease: the progressive motor neuropathy mouse.

PubMed

Wagey, R; Lurot, S; Perrelet, D; Pelech, S L; Sagot, Y; Krieger, C

2001-01-01

A murine model of motoneuron disease, the pmn/pmn mouse, shows a reduction in the retrograde transport of fluorescent probes applied directly onto the cut end of sciatic nerve. Brain-derived neurotrophic factor (BDNF), when co-applied with fluorescent tracers, increases the number of retrograde labelled motoneurons. We demonstrate here that spinal cord tissue from pmn/pmn mice had significantly reduced phosphatidylinositol 3-kinase activity and expression in the particulate fraction compared to controls, without changes in the activities or expression of the downstream kinases, protein kinase B/Akt or Erk1. Systemic administration of BDNF augmented phosphatidylinositol 3-kinase specific activity in spinal cord tissue from pmn/pmn and control mice, with a greater elevation in the particulate fractions of pmn/pmn mice than in controls. We examined the effect of inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase on the retrograde labelling of motoneurons, 24h following the direct application of inhibitors and Fluorogold to the cut end of sciatic nerve in control and pmn/pmn mice (labelling index). The mitogen-activated protein kinase kinase inhibitor PD 98059 had no effect on the labelling index in control or pmn/pmn mice. In the absence of exogenous BDNF, phosphatidylinositol 3-kinase inhibitors reduced the number of labelled motoneurons in control mice, without changing the labelling index in pmn/pmn. Co-application of phosphatidylinositol 3-kinase inhibitors with BDNF to the cut end of sciatic nerve blocked the action of BDNF on retrograde labelling in pmn/pmn mice. These results indicate that the retrograde labelling of motoneurons is mediated by phosphatidylinositol 3-kinase-dependent and -independent pathways. In pmn/pmn mice, phosphatidylinositol 3-kinase activity in spinal neurons is below the level required for optimal retrograde labelling of motoneurons and labelling can be augmented by the administration of growth

Relations among passive electrical properties of lumbar alpha-motoneurones of the cat.

PubMed Central

Gustafsson, B; Pinter, M J

1984-01-01

The relations among passive membrane properties have been examined in cat motoneurones utilizing exclusively electrophysiological techniques. A significant relation was found to exist between the input resistance and the membrane time constant. The estimated electrotonic length showed no evident tendency to vary with input resistance but did show a tendency to decrease with increasing time constant. Detailed analysis of this trend suggests, however, that a variation in dendritic geometry is likely to exist among cat motoneurones, such that the dendritic trees of motoneurones projecting to fast-twitch muscle units are relatively more expansive than those of motoneurones projecting to slow-twitch units. Utilizing an expression derived from the Rall neurone model, the total capacitance of the equivalent cylinder corresponding to a motoneurone has been estimated. With the assumption of a constant and uniform specific capacitance of 1 mu F/cm2, the resulting values have been used as estimates of cell surface area. These estimates agree well with morphologically obtained measurements from cat motoneurones reported by others. Both membrane time constant (and thus likely specific membrane resistivity) and electrotonic length showed little tendency to vary with surface area. However, after-hyperpolarization (a.h.p.) duration showed some tendency to vary such that cells with brief a.h.p. duration were, on average, larger than those with longer a.h.p. durations. Apart from motoneurones with the lowest values, axonal conduction velocity was only weakly related to variations in estimated surface area. Input resistance and membrane time constant were found to vary systematically with the a.h.p. duration. Analysis suggested that the major part of the increase in input resistance with a.h.p. duration was related to an increase in membrane resistivity and a variation in dendritic geometry rather than to differences in surface area among the motoneurones. The possible effects of

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

SciTech Connect

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at differentmore » developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose

Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

NASA Astrophysics Data System (ADS)

Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.

2011-05-01

It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental

Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons

PubMed Central

Krakowiak, Joey; Liu, Caiyue; Papudesu, Chandana; Ward, P. Jillian; Wilhelm, Jennifer C.; English, Arthur W.

2015-01-01

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells. PMID:25918648

Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

PubMed

Nakanishi, S T; Whelan, P J

2010-05-01

During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

Contribution of intrinsic properties and synaptic inputs to motoneuron discharge patterns: a simulation study

PubMed Central

ElBasiouny, Sherif M.; Rymer, W. Zev; Heckman, C. J.

2012-01-01

Motoneuron discharge patterns reflect the interaction of synaptic inputs with intrinsic conductances. Recent work has focused on the contribution of conductances mediating persistent inward currents (PICs), which amplify and prolong the effects of synaptic inputs on motoneuron discharge. Certain features of human motor unit discharge are thought to reflect a relatively stereotyped activation of PICs by excitatory synaptic inputs; these features include rate saturation and de-recruitment at a lower level of net excitation than that required for recruitment. However, PIC activation is also influenced by the pattern and spatial distribution of inhibitory inputs that are activated concurrently with excitatory inputs. To estimate the potential contributions of PIC activation and synaptic input patterns to motor unit discharge patterns, we examined the responses of a set of cable motoneuron models to different patterns of excitatory and inhibitory inputs. The models were first tuned to approximate the current- and voltage-clamp responses of low- and medium-threshold spinal motoneurons studied in decerebrate cats and then driven with different patterns of excitatory and inhibitory inputs. The responses of the models to excitatory inputs reproduced a number of features of human motor unit discharge. However, the pattern of rate modulation was strongly influenced by the temporal and spatial pattern of concurrent inhibitory inputs. Thus, even though PIC activation is likely to exert a strong influence on firing rate modulation, PIC activation in combination with different patterns of excitatory and inhibitory synaptic inputs can produce a wide variety of motor unit discharge patterns. PMID:22031773

Influence of proprioceptive feedback on the firing rate and recruitment of motoneurons

NASA Astrophysics Data System (ADS)

De Luca, C. J.; Kline, J. C.

2012-02-01

We investigated the relationships of the firing rate and maximal recruitment threshold of motoneurons recorded during isometric contraction with the number of spindles in individual muscles. At force levels above 10% of maximal voluntary contraction, the firing rate was inversely related to the number of spindles in a muscle, with the slope of the relationship increasing with force. The maximal recruitment threshold of motor units increased linearly with the number of spindles in the muscle. Thus, muscles with a greater number of spindles had lower firing rates and a greater maximal recruitment threshold. These findings may be explained by a mechanical interaction between muscle fibres and adjacent spindles. During low-level (0% to 10%) voluntary contractions, muscle fibres of recruited motor units produce force twitches that activate nearby spindles to respond with an immediate excitatory feedback that reaches maximal level. As the force increases further, the twitches overlap and tend towards tetanization, the muscle fibres shorten, the spindles slacken, their excitatory firings decrease, and the net excitation to the homonymous motoneurons decreases. Motoneurons of muscles with greater number of spindles receive a greater decrease in excitation which reduces their firing rates, increases their maximal recruitment threshold, and changes the motoneuron recruitment distribution.

Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line.

PubMed

Mosier, D R; Baldelli, P; Delbono, O; Smith, R G; Alexianu, M E; Appel, S H; Stefani, E

1995-01-01

The sporadic form of amyotrophic lateral sclerosis (ALS) is an idiopathic and eventually lethal disorder causing progressive degeneration of cortical and spinal motoneurons. Recent studies have shown that the majority of patients with sporadic ALS have serum antibodies that bind to purified L-type voltage-gated calcium channels and that antibody titer correlates with the rate of disease progression. Furthermore, antibodies purified from ALS patient sera have been found to alter the physiologic function of voltage-gated calcium channels in nonmotoneuron cell types. Using whole-cell patch-clamp techniques, immunoglobulins purified from sera of 5 of 6 patients with sporadic ALS are now shown to increase calcium currents in a hybrid motoneuron cell line, VSC4.1. These calcium currents are blocked by the polyamine funnel-web spider toxin FTX, which has previously been shown to block Ca2+ currents and evoked transmitter release at mammalian motoneuron terminals. These data provide additional evidence linking ALS to an autoimmune process and suggest that antibody-induced increases in calcium entry through voltage-gated calcium channels may occur in motoneurons in this disease, with possible deleterious effects in susceptible neurons.

Characterization of axon formation in the embryonic stem cell-derived motoneuron.

PubMed

Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

2011-01-01

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

Shared Components of Rhythm Generation for Locomotion and Scratching Exist Prior to Motoneurons

PubMed Central

Hao, Zhao-Zhe; Berkowitz, Ari

2017-01-01

Does the spinal cord use a single network to generate locomotor and scratching rhythms or two separate networks? Previous research showed that simultaneous swim and scratch stimulation (“dual stimulation”) in immobilized, spinal turtles evokes a single rhythm in hindlimb motor nerves with a frequency often greater than during swim stimulation alone or scratch stimulation alone. This suggests that the signals that trigger swimming and scratching converge and are integrated within the spinal cord. However, these results could not determine whether the integration occurs in motoneurons themselves or earlier, in spinal interneurons. Here, we recorded intracellularly from hindlimb motoneurons during dual stimulation. Motoneuron membrane potentials displayed regular oscillations at a higher frequency during dual stimulation than during swim or scratch stimulation alone. In contrast, arithmetic addition of the oscillations during swimming alone and scratching alone with various delays always generated irregular oscillations. Also, the standard deviation of the phase-normalized membrane potential during dual stimulation was similar to those during swimming or scratching alone. In contrast, the standard deviation was greater when pooling cycles of swimming alone and scratching alone for two of the three forms of scratching. This shows that dual stimulation generates a single rhythm prior to motoneurons. Thus, either swimming and scratching largely share a rhythm generator or the two rhythms are integrated into one rhythm by strong interactions among interneurons. PMID:28848402

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

PubMed Central

Caraballo-Miralles, Víctor; Cardona-Rossinyol, Andrea; Garcera, Ana; Torres-Benito, Laura; Soler, Rosa M.; Tabares, Lucía; Lladó, Jerònia; Olmos, Gabriel

2013-01-01

Spinal muscular atrophy (SMA) is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN) protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD). In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons. PMID:23759991

Influence of proprioceptive feedback on the firing rate and recruitment of motoneurons

PubMed Central

De Luca, C J; Kline, J C

2012-01-01

We investigated the relationships of the firing rate and maximal recruitment threshold of motoneurons recorded during isometric contraction with the number of spindles in individual muscles. At force levels above 10% of maximal voluntary contraction, the firing rate was inversely related to the number of spindles in a muscle, with the slope of the relationship increasing with force. The maximal recruitment threshold of motor units increased linearly with the number of spindles in the muscle. Thus, muscles with a greater number of spindles had lower firing rates and a greater maximal recruitment threshold. These findings may be explained by a mechanical interaction between muscle fibres and adjacent spindles. During low-level (0 to 10%) voluntary contractions, muscle fibres of recruited motor units produce force-twitches that activate nearby spindles to respond with an immediate excitatory feedback that reaches maximal level. As the force increases further, the twitches overlap and tend towards tetanization, the muscle fibres shorten, the spindles slacken, their excitatory firings decrease, and the net excitation to the homonymous motoneurons decreases. Motoneurons of muscles with greater number of spindles receive a greater decrease in excitation which reduces their firing rates, increases their maximal recruitment threshold, and changes the motoneuron recruitment distribution. PMID:22183300

Isolated abducens nerve palsy associated with subarachnoid hemorrhage: a localizing sign of ruptured posterior inferior cerebellar artery aneurysms.

PubMed

Burkhardt, Jan-Karl; Winkler, Ethan A; Lasker, George F; Yue, John K; Lawton, Michael T

2018-06-01

OBJECTIVE Compressive cranial nerve syndromes can be useful bedside clues to the diagnosis of an enlarging intracranial aneurysm and can also guide subsequent evaluation, as with an acute oculomotor nerve (cranial nerve [CN] III) palsy that is presumed to be a posterior communicating artery aneurysm and a surgical emergency until proven otherwise. The CN VI has a short cisternal segment from the pontomedullary sulcus to Dorello's canal, remote from most PICA aneurysms but in the hemodynamic pathway of a rupturing PICA aneurysm that projects toward Dorello's canal. The authors describe a cranial nerve syndrome for posterior inferior cerebellar artery (PICA) aneurysms that associates subarachnoid hemorrhage (SAH) and an isolated abducens nerve (CN VI) palsy. METHODS Clinical and radiological data from 106 surgical patients with PICA aneurysms (66 ruptured and 40 unruptured) were retrospectively reviewed. Data from a group of 174 patients with other aneurysmal SAH (aSAH) were analyzed in a similar manner to control for nonspecific effects of SAH. Univariate statistical analysis compared incidence and risk factors associated with CN VI palsy in subarachnoid hemorrhage. RESULTS Overall, 13 (4.6%) of 280 patients had CN VI palsy at presentation, and all of them had ruptured aneurysms (representing 13 [5.4%] of the 240 cases of ruptured aneurysms). CN VI palsies were observed in 12 patients with ruptured PICA aneurysms (12/66 [18.1%]) and 1 patient with other aSAH (1/174 [0.1%], p < 0.0001). PICA aneurysm location in ruptured aneurysms was an independent predictor for CN VI palsy on multivariate analysis (p = 0.001). PICA aneurysm size was not significantly different in patients with or without CN VI palsy (average size 4.4 mm and 5.2 mm, respectively). Within the PICA aneurysm cohort, modified Fisher grade (p = 0.011) and presence of a thick cisternal SAH (modified Fisher Grades 3 and 4) (p = 0.003) were predictors of CN VI palsy. In all patients with ruptured PICA

F-wave of single firing motor units: correct or misleading criterion of motoneuron excitability in humans?

PubMed

Kudina, Lydia P; Andreeva, Regina E

2017-03-01

Motoneuron excitability is a critical property for information processing during motor control. F-wave (a motoneuronal recurrent discharge evoked by a motor antidromic volley) is often used as a criterion of motoneuron pool excitability in normal and neuromuscular diseases. However, such using of F-wave calls in question. The present study was designed to explore excitability of single low-threshold motoneurons during their natural firing in healthy humans and to ascertain whether F-wave is a correct measure of motoneuronal excitability. Single motor units (MUs) were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms and motoneuron excitability changes within a target interspike interval were analysed during testing by motor antidromic and Ia-afferent volleys. It was found that F-waves could be occasionally recorded in some low-threshold MUs. However, during evoking F-wave, in contrast with the H-reflex, peri-stimulus time histograms revealed no statistically significant increase in MU discharge probability. Moreover, surprisingly, motoneurons appeared commonly incapable to fire a recurrent discharge within the most excitable part of a target interval. Thus, the F-wave, unlike the H-reflex, is the incorrect criterion of motoneuron excitability resulting in misleading conclusions. However, it does not exclude the validity of the F-wave as a clinical tool for other aims. It was concluded that the F-wave was first explored in low-threshold MUs during their natural firing. The findings may be useful at interpretations of changes in the motoneuron pool excitability in neuromuscular diseases.

Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats.

PubMed Central

Grimwood, P D; Appenteng, K; Curtis, J C

1992-01-01

1. Our aim has been to quantify the monosynaptic connections of trigeminal interneurones and spindle afferents onto jaw-elevator motoneurones as a step towards identifying common features in organization of monosynaptic inputs onto motoneurones. We have used the intracellular variant of the spike-triggered averaging method to examine the connections of single identified trigeminal interneurones and jaw-elevator muscle spindle afferents onto single jaw-elevator motoneurones. The interneurones examined lay in the region immediately caudal to the trigeminal motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Ten EPSPs and eight IPSPs were obtained from examining the connections of seventeen interneurones to thirty-six motoneurones, suggesting a functional connectivity of 50% for individual interneurones onto elevator motoneurones. Fourteen EPSPs were obtained from examining the connections of thirteen spindle afferents onto twenty-seven motoneurones, giving a functional connectivity of 52% for individual spindle afferents onto elevator motoneurones. The amplitudes of the EPSPs elicited by interneurones ranged from 7-48 microV (mean = 17, S.D. = 12.5, n = 10) and from 7 to 289 microV (mean = 64, S.D. = 76.0, n = 14) for the spindle-mediated EPSPs; the difference in the two means was not significant (P = 0.07). 3. However, the amplitude of averaged responses obtained by signal averaging methods are dependent on the assumption that the postsynaptic response occurs following every impulse in the presynaptic neurone. We therefore estimated the percentage of sweeps which contained EPSPs triggered by the presynaptic neurone under study. In essence the method used consisted of visual inspection of the individual sweeps comprising an average in order to assess the occurrence of EPSPs within six separate time windows, each of duration +/- 0.3 ms. Five windows were placed at randomly selected times on

Increases in human motoneuron excitability after cervical spinal cord injury depend on the level of injury.

PubMed

Thomas, Christine K; Häger, Charlotte K; Klein, Cliff S

2017-02-01

After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single-unit level F waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F waves were evident in all 4 participants with C 4 -level SCI, absent in 8 with C 5 or C 6 injury, and present in 6 of 12 Uninjured participants (P < 0.001). The percentage of units that generated F waves differed across groups (C 4 : 30%, C 5 or C 6 : 0%, Uninjured: 16%; P < 0.001). Mean (±SD) proximal axon conduction velocity was slower after C 4 SCI [64 ± 4 m/s (n = 6 units), Uninjured: 73 ± 8 m/s (n = 7 units); P = 0.037]. Mean distal axon conduction velocity differed by group [C 4 : 40 ± 8 m/s (n = 20 units), C 5 or C 6 : 49 ± 9 m/s (n = 28), Uninjured: 60 ± 7 m/s (n = 45); P < 0.001]. Motor unit properties (EMG amplitude, twitch force) only differed after SCI (P ≤ 0.004), not by injury level. Motor units with F waves had distal conduction velocities, M-wave amplitudes, and twitch forces that spanned the respective group range, indicating that units with heterogeneous properties produced F waves. Recording unitary F waves has shown that thenar motoneurons closer to the SCI (C 5 or C 6 ) have reduced excitability whereas those further away (C 4 ) have increased excitability, which may exacerbate muscle spasms. This difference in motoneuron excitability may be related to the extent of membrane depolarization following SCI. Unitary F waves were common in paralyzed thenar muscles of people who had a chronic spinal cord injury (SCI) at the C 4 level compared with uninjured people, but F waves did not occur in people that had SCI at the C 5 or C 6 level. These results highlight that intrinsic motoneuron

Neuronal Basis of Crossed Actions from the Reticular Formation on Feline Hindlimb Motoneurons

PubMed Central

Jankowska, Elzbieta; Hammar, Ingela; Slawinska, Urszula; Maleszak, Katarzyna; Edgley, Stephen A.

2007-01-01

Pathways through which reticulospinal neurons can influence contralateral limb movements were investigated by recording from mo-toneurons innervating hindlimb muscles. Reticulospinal tract fibers were stimulated within the brainstem or in the lateral funiculus of the thoracic spinal cord contralateral to the motoneurons. Effects evoked by ipsilaterally descending reticulospinal tract fibers were eliminated by a spinal hemisection at an upper lumbar level. Stimuli applied in the brainstem evoked EPSPs, IPSPs, or both at latencies of 1.42 ± 0.03 and 1.53 ± 0.04 msec, respectively, from the first components of the descending volleys and with properties indicating a disynaptic linkage, in most contralateral motoneurons: EPSPs in 76% and IPSPs in 26%. EPSPs with characteristics of monosynaptically evoked responses, attributable to direct actions of crossed axon collaterals of reticulospinal fibers, were found in a small proportion of the motoneurons, whether evoked from the brainstem (9%) or from the thoracic cord (12.5%). Commissural neurons, which might mediate the crossed disynaptic actions (i.e., were antidromically activated from contralateral motor nuclei and monosynaptically excited from the ipsilateral reticular formation), were found in Rexed’s lamina VIII in the midlumbar segments (L3–L5). The results reveal that although direct actions of reticulospinal fibers are much more potent on ipsilateral motoneurons, interneuronally mediated actions are as potent contralaterally as ipsilaterally, and midlumbar commissural neurons are likely to contribute to them. They indicate a close coupling between the spinal interneuronal systems used by the reticulospinal neurons to coordinate muscle contractions ipsilaterally and contralaterally. PMID:12629191

cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae.

PubMed

Krill, Jennifer L; Dawson-Scully, Ken

2016-01-01

While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia.

Immunohistochemical localization of serotonin- and substance P-containing fibers around respiratory muscle motoneurons in the nucleus ambiguus of the cat.

PubMed

Holtman, J R

1988-07-01

Retrograde tracing with a fluorescent dye (Fast Blue) combined with immunohistochemistry was used to determine if the putative neurotransmitters, serotonin and substance P, are present around posterior cricoarytenoid muscle motoneurons. Fast Blue was injected into the posterior cricoarytenoid muscle of the larynx. Following a 14-21 day survival time to allow for transport of the dye, the animals were perfusion fixed and the brainstem was removed for analysis under the fluorescence microscope. Retrogradely labeled cell bodies containing Fast Blue were found within the nucleus ambiguus from 0.5 to 3.0 mm rostral to obex. These motoneurons ranged in size from 23 to 38 micron. The same tissue sections containing labeled posterior cricoarytenoid muscle motoneurons were then used to determine the distribution of serotonin and substance P around these motoneurons using the indirect immunofluorescence technique. A dense network of serotonin-containing immunoreactive fibers was found around posterior cricoarytenoid muscle motoneurons. The fibers contained varicosities which were in close proximity, actually appearing to surround these motoneurons. Substance P immunoreactive fibers and varicosities were also found around posterior cricoarytenoid muscle motoneurons. The density and pattern of distribution of the substance P immunoreactivity was similar to that of the serotonin immunoreactivity. These results suggest that these putative neurotransmitters may be involved in influencing the activity of posterior cricoarytenoid muscle motoneurons. Serotonin and substance P are also present around other respiratory motoneurons such as phrenic motoneurons. Therefore, these two neurotransmitters may have a more general role in influencing respiratory motor outflow.

Estimates of the location of L-type Ca2+ channels in motoneurons of different sizes: a computational study.

PubMed

Grande, Giovanbattista; Bui, Tuan V; Rose, P Ken

2007-06-01

In the presence of monoamines, L-type Ca(2+) channels on the dendrites of motoneurons contribute to persistent inward currents (PICs) that can amplify synaptic inputs two- to sixfold. However, the exact location of the L-type Ca(2+) channels is controversial, and the importance of the location as a means of regulating the input-output properties of motoneurons is unknown. In this study, we used a computational strategy developed previously to estimate the dendritic location of the L-type Ca(2+) channels and test the hypothesis that the location of L-type Ca(2+) channels varies as a function of motoneuron size. Compartmental models were constructed based on dendritic trees of five motoneurons that ranged in size from small to large. These models were constrained by known differences in PIC activation reported for low- and high-conductance motoneurons and the relationship between somatic PIC threshold and the presence or absence of tonic excitatory or inhibitory synaptic activity. Our simulations suggest that L-type Ca(2+) channels are concentrated in hotspots whose distance from the soma increases with the size of the dendritic tree. Moving the hotspots away from these sites (e.g., using the hotspot locations from large motoneurons on intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold that occur experimentally during tonic excitatory or inhibitory synaptic activity. In models equipped with a size-dependent distribution of L-type Ca(2+) channels, the amplification of synaptic current by PICs depends on motoneuron size and the location of the synaptic input on the dendritic tree.

Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse

PubMed Central

Falgairolle, Melanie; Puhl, Joshua G; Pujala, Avinash; Liu, Wenfang; O’Donovan, Michael J

2017-01-01

Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase neurons (ChAT+) or Arch in LIM-homeodomain transcription factor Isl1+ neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT+ or Isl1+ neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm. When the light was turned off motoneuron firing and locomotor frequency both transiently increased. These effects were not due to cholinergic neurotransmission, persisted during partial blockade of gap junctions and were mediated, in part, by AMPAergic transmission. In spinal cords expressing ChR2, illumination increased motoneuron discharge and transiently accelerated the rhythm. We conclude that motoneurons provide feedback to the central pattern generator (CPG) during drug-induced locomotor-like activity. DOI: http://dx.doi.org/10.7554/eLife.26622.001 PMID:28671548

Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.

1989-01-01

The descending pathways to the motoneuronal cell group of the cutaneous trunci muscle (CTM) of the cat were investigated by injecting H-3-labeled lucine into the brain stem, the diencephalon, or the C1, C2, C6, and C8 segments of the spinal cord, and examining fixed autoradiographic sections of the spinal cord and brain regions. Results demonstrate presence of specific supraspinal projectons to the CTM motor nucleus originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum. Results also suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections to all other motoneuronal cell groups surrounding the CTM nucleus are very strong.

α-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.

PubMed

MacDonell, Christopher W; Chopek, Jeremy W; Gardiner, Kalan R; Gardiner, Phillip F

2017-10-01

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP 1/2 ) was found in low-conductance MN for the diabetic group only, whereas AHP½ tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHP amp ), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP 1/2 decay and the tendency for a reduction in AHP amp may be the first sign of change to MN function. NEW & NOTEWORTHY Knowledge about the impact of obesity and diabetes on the biophysical properties of motoneurons is lacking. We found that diabetes reduces the duration of the afterhyperpolarization and that motoneuron function is unchanged by obesity. A reduced afterhyperpolarization may impact discharge characteristics and may be the first sign of change to motoneuron function. Copyright �

Mechanisms and functional implications of motoneuron adaptations to increased physical activity.

PubMed

MacDonell, Christopher; Gardiner, Phillip

2018-06-01

Motoneurons demonstrate adaptations in their physiological properties to alterations in chronic activity levels. The most consistent change that appears to result from endurance-type exercise training is the reduced excitatory current required to initiate and maintain rhythmic firing. While the precise mechanisms through which these neurons adapt to activity are currently unknown, evidence exists that adaptation may involve alterations in the expression of genes that code for membrane receptors which can influence the responses of neurons to transmitters during activation. The influence of these adaptations may also extend to the resting condition, where ambient levels of neuroactive substances may influence ion conductances at rest, and thus result in the activation or inhibition of specific ion conductances that underlie the measurements of increased excitability that have been reported for motoneurons in the anesthetised state. We have applied motoneuron excitability and muscle unit contractile changes with endurance training to a mathematical computerised model of motor unit recruitment (Heckman and Binder, 1991). The results from the modelling exercise demonstrate increased task efficiency at relative levels of effort during a submaximal contraction. The physiological impact that nerve and muscle adaptations have on the neuromuscular system during standardized tasks seem to fit with reported changes in motor unit behaviour in trained human subjects.

Vesicular glutamate transporter 1 (VGLUT1)- and VGLUT2-immunopositive axon terminals on the rat jaw-closing and jaw-opening motoneurons.

PubMed

Park, Sook Kyung; Ko, Sang Jin; Paik, Sang Kyoo; Rah, Jong-Cheol; Lee, Kea Joo; Bae, Yong Chul

2018-02-23

To provide information on the glutamatergic synapses on the trigeminal motoneurons, which may be important for understanding the mechanism of control of jaw movements, we investigated the distribution of vesicular glutamate transporter (VGLUT)1-immunopositive (+) and VGLUT2 + axon terminals (boutons) on the rat jaw-closing (JC) and jaw-opening (JO) motoneurons, and their morphological determinants of synaptic strength by retrograde tracing, electron microscopic immunohistochemistry, and quantitative ultrastructural analysis. We found that (1) the large majority of VGLUT + boutons on JC and JO motoneurons were VGLUT2+, (2) the density of VGLUT1 + boutons terminating on JC motoneurons was significantly higher than that on JO motoneurons, (3) the density of VGLUT1 + boutons terminating on non-primary dendrites of JC motoneurons was significantly higher than that on somata or primary dendrites, whereas the density of VGLUT2 + boutons was not significantly different between JC and JO motoneurons and among various compartments of the postsynaptic neurons, and (4) the bouton volume, mitochondrial volume, and active zone area of the VGLUT1 + boutons forming synapses on JC motoneurons were significantly bigger than those of VGLUT2 + boutons. These findings suggest that JC and JO motoneurons receive glutamatergic input primarily from VGLUT2-expressing intrinsic neurons (premotoneurons), and may be controlled differently by neurons in the trigeminal mesencephalic nucleus and by glutamatergic premotoneurons.

Effects of calcium (Ca(2+)) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: insight from a mathematical model.

PubMed

Horn, Kyle G; Solomon, Irene C

2014-01-01

Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca(2+), which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca(2+) and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca(2+) handling processes. For the current study, a series of HM models that include Ca(2+) pumps, Na(+)/Ca(2+) exchangers, and a generic exponential decay of excess Ca(2+) were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca(2+)-related mechanisms: BK channels, Ca(2+) buffering, and diffusion of [Ca(2+)]i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca(2+) seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca(2+) appears to be necessary for capturing longer term frequency changes. © 2014 Elsevier B.V. All rights reserved.

Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

PubMed Central

Gladden, M H; Matsuzaki, H

2002-01-01

Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

The membrane properties and firing characteristics of rat jaw-elevator motoneurones.

PubMed Central

Moore, J; Appenteng, K

1990-01-01

1. We have determined the membrane and firing properties of fifty-six jaw-elevator motoneurones in rats that were anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Forty-two neurones were identified as masseter motoneurones and fourteen as masseter synergist motoneurones. The membrane potentials for the sample ranged from -60 to -86 (mean = -68; S.D. = 7.3; n = 56), and spike amplitudes from 50 to 95 mV. The duration of the after-hyperpolarization following antidromic spikes in masseter motoneurones ranged from 15 to 50 ms (mean = 30; S.D. = 12.8) and their amplitudes from 1.0 to 4.5 mV (mean = 2.7; S.D. = 2.2; n = 42). 3. The mean input resistance for the total sample was 2.3 M omega (S.D. = 0.9; n = 56), membrane time constant 3.9 ms (S.D. = 0.9; n = 48) and rheobase 4.2 nA (S.D. = 2.6; n = 56). The distribution of these parameters was independent of membrane potential. We found no significant interrelationships between the membrane properties and one interpretation of this is that our sample may be drawn from a homogenous population of motoneurones. We also suggest that elevator motoneurones may have a lower Rm (specific membrane resistivity) value than cat hindlimb motoneurones because they have a similar range of input resistance values but only half the total surface area. 4. Forty-six out of forty-nine neurones fired repetitively to a depolarizing current pulse at a mean threshold of 1.6 x rheobase. Current-frequency plots were constructed for thirteen neurones and all but one showed a primary and secondary range in the firing of the first interspike interval. The mean slope in the primary range was 31 impulses s-1 nA-1 and 77 impulses s-1 nA-1 for the secondary range. The mean minimal firing frequency for steady firing was 26 impulses s-1 and, in response to an increase of stimulation, the rate increased monotonically with a slope of 11 impulses s-1 nA-1. 5. The dynamic sensitivity of twelve neurones was assessed from their

Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish

PubMed Central

Haehnel-Taguchi, Melanie; Akanyeti, Otar

2014-01-01

The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 μm/ms. However, spike rate did not change when the cupula was deflected below 8 μm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior. PMID:24966296

Properties of human motoneurones and their synaptic noise deduced from motor unit recordings with the aid of computer modelling.

PubMed

Matthews, P B

1999-01-01

This paper reviews two new facets of the behaviour of human motoneurones; these were demonstrated by modelling combined with analysis of long periods of low-frequency tonic motor unit firing (sub-primary range). 1) A novel transformation of the interval histogram has shown that the effective part of the membrane's post-spike voltage trajectory is a segment of an exponential (rather than linear), with most spikes being triggered by synaptic noise before the mean potential reaches threshold. The curvature of the motoneurone's trajectory affects virtually all measures of its behaviour and response to stimulation. The 'trajectory' is measured from threshold, and so includes any changes in threshold during the interspike interval. 2) A novel rhythmic stimulus (amplitude-modulated pulsed vibration) has been used to show that the motoneurone produces appreciable phase-advance during sinusoidal excitation. At low frequencies, the advance increases with rising stimulus frequency but then, slightly below the motoneurones mean firing rate, it suddenly becomes smaller. The gain has a maximum for stimuli at the mean firing rate (the 'carrier'). Such behaviour is functionally important since it affects the motoneurone's response to any rhythmic input, whether generated peripherally by the receptors (as in tremor) or by the CNS (as with cortical oscillations). Low mean firing rates favour tremor, since the high gain and reduced phase advance at the 'carrier' reduce the stability of the stretch reflex.

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

Regulation of Survival Motor Neuron Protein by the Nuclear Factor-Kappa B Pathway in Mouse Spinal Cord Motoneurons.

PubMed

Arumugam, Saravanan; Mincheva-Tasheva, Stefka; Periyakaruppiah, Ambika; de la Fuente, Sandra; Soler, Rosa M; Garcera, Ana

2018-06-01

Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease. Using a lentiviral-based shRNA approach to reduce the expression of several members of NF-κB pathway, we observed that IKK and RelA knockdown caused Smn reduction in mouse-cultured motoneurons whereas IKK or RelB knockdown did not. Moreover, isolated motoneurons obtained from the severe SMA mouse model showed reduced protein levels of several NF-κB members and RelA phosphorylation. We describe the alteration of NF-κB pathway in SMA cells. In the context of recent studies suggesting regulation of altered intracellular pathways as a future pharmacological treatment of SMA, we propose the NF-κB pathway as a candidate in this new therapeutic approach.

Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat

PubMed Central

Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

2013-01-01

Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

PubMed Central

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

The morphology and electrical geometry of rat jaw-elevator motoneurones.

PubMed Central

Moore, J A; Appenteng, K

1991-01-01

1. The aim of this work was to quantify both the morphology and electrical geometry of the dendritic trees of jaw-elevator motoneurones. To do this we have made intracellular recordings from identified motoneurones in anaesthetized rats, determined their membrane properties and then filled them with horseradish peroxidase by ionophoretic ejection. Four neurones were subsequently fully reconstructed and the lengths and diameters of all the dendritic segments measured. 2. The mean soma diameter was 25 microns and values of mean dendritic length for individual cells ranged from 514 to 773 microns. Dendrites branched on average 9.1 times to produce 10.2 end-terminations. Dendritic segments could be represented as constant diameter cylinders between branch points. Values of dendritic surface area ranged from 1.08 to 2.52 x 10(5) microns 2 and values of dendritic to total surface area from 98 to 99%. 3. At branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was exactly 1.0. Therefore the individual branch points could be collapsed into a single cylinder. Furthermore for an individual dendrite the diameter of this cylinder remained constant with increasing electrical distance from the soma. Thus individual dendrites can be represented electrically as cylinders of constant diameter. 4. However dendrites of a given neurone terminated at different electrical distances from the soma. The equivalent-cylinder diameter of the combined dendritic tree remained constant over the proximal half and then showed a pronounced reduction over the distal half. The reduction in equivalent diameter could be ascribed to the termination of dendrites at differing electrical distances from the soma. Therefore the complete dendritic tree of these motoneurones is best represented as a cylinder over the proximal half of their electrical length but as a cone over the distal half. PMID:1804966

Activation properties of trigeminal motoneurons in participants with and without bruxism

PubMed Central

D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

2013-01-01

In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

PubMed Central

Kurihara, T; Yoshioka, K; Otsuka, M

1995-01-01

1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones. PMID:7562617

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

PubMed

Kurihara, T; Yoshioka, K; Otsuka, M

1995-06-15

1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones.

Astrocytes expressing mutant SOD1 and TDP43 trigger motoneuron death that is mediated via sodium channels and nitroxidative stress

PubMed Central

Rojas, Fabiola; Cortes, Nicole; Abarzua, Sebastian; Dyrda, Agnieszka; van Zundert, Brigitte

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by dysfunction and degeneration of motor neurons. Multiple disease-causing mutations, including in the genes for SOD1 and TDP-43, have been identified in ALS. Astrocytes expressing mutant SOD1 are strongly implicated in the pathogenesis of ALS: we have shown that media conditioned by astrocytes carrying mutant SOD1G93A contains toxic factor(s) that kill motoneurons by activating voltage-sensitive sodium (Nav) channels. In contrast, a recent study suggests that astrocytes expressing mutated TDP43 contribute to ALS pathology, but do so via cell-autonomous processes and lack non-cell-autonomous toxicity. Here we investigate whether astrocytes that express diverse ALS-causing mutations release toxic factor(s) that induce motoneuron death, and if so, whether they do so via a common pathogenic pathway. We exposed primary cultures of wild-type spinal cord cells to conditioned medium derived from astrocytes (ACM) that express SOD1 (ACM-SOD1G93A and ACM-SOD1G86R) or TDP43 (ACM-TDP43A315T) mutants; we show that such exposure rapidly (within 30–60 min) increases dichlorofluorescein (DCF) fluorescence (indicative of nitroxidative stress) and leads to extensive motoneuron-specific death within a few days. Co-application of the diverse ACMs with anti-oxidants Trolox or esculetin (but not with resveratrol) strongly improves motoneuron survival. We also find that co-incubation of the cultures in the ACMs with Nav channel blockers (including mexiletine, spermidine, or riluzole) prevents both intracellular nitroxidative stress and motoneuron death. Together, our data document that two completely unrelated ALS models lead to the death of motoneuron via non-cell-autonomous processes, and show that astrocytes expressing mutations in SOD1 and TDP43 trigger such cell death through a common pathogenic pathway that involves nitroxidative stress, induced at least in part by Nav channel activity. PMID:24570655

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

Motoneuron firing and isomyosin type of muscle fibres in prior polio.

PubMed Central

Borg, K; Borg, J; Dhoot, G; Edström, L; Grimby, L; Thornell, L E

1989-01-01

In patients with prior polio there was an excessive use of remaining motor units and an absence of type II muscle fibres in the tibialis anterior (TA). In the present study, eight subjects with prior polio with more than 90% type I fibres in the TA were examined. The aim was to elucidate whether the lack of type II muscle fibres was due to a selective loss of motoneurons with high threshold and high axonal conduction velocity or due to a muscle fibre transition from type II to type I. There was no decrease of the proportion of motoneurons with high threshold and high axonal conduction velocity. Monoclonal antibodies against fast and slow myosin heavy chains (MHC) were used as histochemical markers and many muscle fibres of type I according to ATPase stainability showed a binding of both anti-fast and anti-slow MHC. It is suggested that the type I muscle fibre dominance in prior polio subjects with excessive use of TA during walking is due to a muscle fibre transition from type II to type I and not to a loss of one class of motor units. Images PMID:2529353

Selective Requirement for Maintenance of Synaptic Contacts onto Motoneurons by Target-Derived trkB Receptors

PubMed Central

2016-01-01

Synaptic contacts onto motoneurons were studied in mice in which the gene for the trkB neurotrophin receptor was knocked out selectively in a subset of spinal motoneurons. The extent of contacts by structures immunoreactive for either of two different vesicular glutamate transporters (VGLUT1 and VGLUT2), the vesicular GABA transporter, or glutamic acid decarboxylase 67 (GAD67) with the somata of motoneurons, was studied in wild type and trkB knockout cells in tamoxifen treated male and female SLICK-trkB−/− mice. Selective knockout of the trkB gene resulted in a marked reduction in contacts made by VGLUT2- and GAD67-immunoreactive structures in both sexes and a significant reduction in contacts containing only glycine in male mice. No reduction was found for glycinergic contacts in female mice or for VGLUT1 immunoreactive contacts in either sex. Signaling through postsynaptic trkB receptors is considered to be an essential part of a cellular mechanism for maintaining the contacts of some, but not all, synaptic contacts onto motoneurons. PMID:27433358

Immunohistochemical study of motoneurons in lumbar spinal cord of c57black/6 mice after 30-days space flight

NASA Astrophysics Data System (ADS)

Tyapkina, Oksana; Islamov, Rustem; Nurullin, Leniz; Petrov, Konstantin.; Rezvyakov, Pavel; Nikolsky, Evgeny

To investigate mechanisms of hypogravity motor syndrome development the immunoexpression of heat shock proteins (Hsp27 and Hsp70), proteins of synaptic transmission (Synaptophysin and PSD95) and neuroprotective proteins (VEGF and Flt-1) in motoneurons of lumbar spinal cord in c57black/6 control mice (n=2) and after 30-days space flight (n=2) was studied. For a quantitative assessment of target proteins level in motoneurons frozen cross sections of lumbar spinal cord were underwent to immunohistochemical staining. Primary antibodies against VEGF, Flt-1, Hsp27 and Hsp70 (SantaCruz Biotechnology, inc. USA), against Synaptophysin and PSD95 (Abcam plc, UK) were visualized by streptavidin-biotin method. Images of spinal cords were received using OlympusBX51WI microscope with AxioCamMRm camera (CarlZeiss, Germany) and the AxioVisionRel. 4.6.3 software (CarlZeiss, Germany). The digitized data were analyzed using ImageJ 1.43 software (NIH, the USA). Quantitively, protein level in motoneurons was estimated by the density of immunoprecipitation. Results of research have not revealed any reliable changes in the immunnoexpression of vascular endothelial growth factor (VEGF) and its Flt-1 receptor in motoneurons of lumbar spinal cord in control and in mice after 30-day space flight. Studying of heat shock proteins, such as Hsp27 and Hsp70, revealed the decrease in level of these proteins immunoexpression in motoneurons of mice from flight group by 15% and 10%, respectively. Some decrease in level of immunnoexpression of presynaptic membrane proteins (synaptophysin, by 21%) and proteins of postsynaptic area (PSD95, by 55%) was observed after space flight. The data obtained testify to possible changes in a functional state (synaptic activity and stress resistance) of motoneurons of lumbar spinal cord in mice after space flight. Thus, we obtained new data on involvement of motoneurons innervating skeletal muscles in development of hypogravity motor syndrome. Research was supported

hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

PubMed

Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

2018-03-20

Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

PubMed Central

Fenik, Victor B.; Davies, Richard O.; Kubin, Leszek

2017-01-01

Rationale Studies of hypoglossal (XII) motoneurons that innervate the genioglossus muscle, an upper airway dilator, suggested that the suppression of upper airway motor tone during REM sleep is caused by withdrawal of excitation mediated by norepinephrine and serotonin. Objectives Our objectives were to determine whether antagonism of aminergic receptors located in the XII nucleus region can abolish the REM sleep–like atonia of XII motoneurons, and whether both serotonergic and noradrenergic antagonists are required to achieve this effect. Methods REM sleep–like episodes were elicited in anesthetized rats by pontine carbachol injections before and at various times after microinjection of prazosin and methysergide combined, or of only one of the drugs, into the XII nucleus. Measurements and Main Results Spontaneous XII nerve activity was significantly reduced, by 35 to 81%, by each antagonist alone and in combination, indicating that XII motoneurons were under both noradrenergic and serotonergic endogenous excitatory drives. During the 32 to 81 min after microinjections of both antagonists, pontine carbachol caused no depression of XII nerve activity, whereas other characteristic effects (activation of the hippocampal and cortical EEG, and slowing of the respiratory rate) remained intact. A partial recovery of the depressant effect of carbachol then occurred parallel to the recovery of spontaneous XII nerve activity from the depressant effect of the antagonists. Microinjections of either antagonist alone did not eliminate the depressant effect of carbachol. Conclusions The REM sleep–like depression of XII motoneuronal activity induced by pontine carbachol can be fully accounted for by the combined withdrawal of noradrenergic and serotonergic effects on XII motoneurons. PMID:16100007

The canonical nuclear factor-κB pathway regulates cell survival in a developmental model of spinal cord motoneurons.

PubMed

Mincheva, Stefka; Garcera, Ana; Gou-Fabregas, Myriam; Encinas, Mario; Dolcet, Xavier; Soler, Rosa M

2011-04-27

In vivo and in vitro motoneuron survival depends on the support of neurotrophic factors. These factors activate signaling pathways related to cell survival or inactivate proteins involved in neuronal death. In the present work, we analyzed the involvement of the nuclear factor-κB (NF-κB) pathway in mediating mouse spinal cord motoneuron survival promoted by neurotrophic factors. This pathway comprises ubiquitously expressed transcription factors that could be activated by two different routes: the canonical pathway, associated with IKKα/IKKβ kinase phosphorylation and nuclear translocation RelA (p65)/p50 transcription factors; and the noncanonical pathway, related to IKKα kinase homodimer phosphorylation and RelB/p52 transcription factor activation. In our system, we show that neurotrophic factors treatment induced IKKα and IKKβ phosphorylation and RelA nuclear translocation, suggesting NF-κB pathway activation. Protein levels of different members of the canonical or noncanonical pathways were reduced in a primary culture of isolated embryonic motoneurons using an interference RNA approach. Even in the presence of neurotrophic factors, selective reduction of IKKα, IKKβ, or RelA proteins induced cell death. In contrast, RelB protein reduction did not have a negative effect on motoneuron survival. Together these results demonstrated that the canonical NF-κB pathway mediates motoneuron survival induced by neurotrophic factors, and the noncanonical pathway is not related to this survival effect. Canonical NF-κB blockade induced an increase of Bim protein level and apoptotic cell death. Bcl-x(L) overexpression or Bax reduction counteracted this apoptotic effect. Finally, RelA knockdown causes changes of CREB and Smn protein levels.

A Simulation Based Analysis of Motor Unit Number Index (MUNIX) Technique Using Motoneuron Pool and Surface Electromyogram Models

PubMed Central

Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

2013-01-01

Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

PubMed Central

Yasuda, Kouichi; Robinson, Dean M; Selvaratnam, Subramaniam R; Walsh, Carmen W; McMorland, Angus J C; Funk, Gregory D

2001-01-01

The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary-slice preparations from neonatal mice (postnatal day 0–3). Local application of the NK1 agonist [SAR9,Met (O2)11]-SP (SPNK1) produced a dose-dependent, spantide- (a non-specific NK receptor antagonist) and GR82334-(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. Under current clamp, SPNK1 significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency-current relationships without affecting slope. Under voltage clamp, SPNK1 evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SPNK1 currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected EK. Effects of the α1-noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SPNK1. Moreover, SPNK1 currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and α1-noradrenergic receptors. In spite of the similar actions of SPNK1 and PE on XII MN responses to somally injected current, α1-noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SPNK1-sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. In contrast to phrenic MNs (Ptak et al. 2000), blocking NMDA

Effects of stimulation of phrenic afferents on cervical respiratory interneurones and phrenic motoneurones in cats.

PubMed Central

Iscoe, S; Duffin, J

1996-01-01

1. In ten decerebrate, paralysed and ventilated cats, we tested the hypothesis that cervical (C5) respiratory interneurones mediate inhibition of phrenic motoneurone activity resulting from single shocks to the phrenic nerve. 2. Stimulus intensities sufficient to activate all afferents elicited (latency, 4.0 +/- 0.9 ms, mean +/- S.D.) a graded suppression of ipsilateral, but not contralateral (five of seven cats) phrenic nerve activity lasting, in six of seven cats, more than 70 ms and interrupted by a brief (approximately 6-18 ms duration) excitation at latencies between 7 and 30 ms. 3. In twenty-five ipsilateral motoneurones, peristimulus time average of the membrane potentials (-61 +/- 10 mV) showed no effect in eleven; of the fourteen that responded, ten had initial EPSPs (latency, 17.6 +/- 3.0 ms) and four initial IPSPs (latencies, 2.25-4.3 ms). Only one motoneurone had both. No responses with latencies > 60 ms were observed. 4. Peristimulus time averages of extracellular activity of thirty ipsilateral interneurones, twenty-five firing in inspiration (I) and five in expiration (E), showed diverse responses. The initial response of I interneurones was an excitation in eleven, a suppression of activity in nine, and no response in five. Latencies of excitations ranged from 2 to 36.5 ms (median, 14 ms) with durations ranging from 2 to 7 ms (mean, 4.4 +/- 1.6 ms). Latencies of suppression of activity ranged from 2 to 29 ms (median, 10 ms). Two E interneurones were excited (latencies, 11 and 15 ms; durations, 3.5 and 2 ms), two inhibited (latencies, 2 and 12 ms; durations, > 40 and 17 ms, respectively), and one did not respond. 5. In nine interneurones (seven I, two E), peristimulus time averages of the membrane potentials (mean, -62 +/- 14 mV) revealed no effect on three (all I). Of the six that responded, four (three I) had initial IPSPs, two (one I, one E) initial EPSPs. EPSPs had latencies of 11.5 (I interneurone) and 22 ms (E interneurone); the latencies of the

Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.

1989-01-01

Pathways involved in the cutaneous trunci muscle (CTM) reflex in the cat were investigated. Experimental animals were injected with tritium-labeled L-leucine into their spinal cord, brain stem, or diencephalon and, after six weeks, perfused with 10-percent formalin. The brains and spinal cords were postfixed in formalin and were cut into transverse 25-micron-thick frozen sections for autoradiography. Results based on injections in the C1, C2, C6, and C8 segments suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do no exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. The results also demonstrate presence of specific supraspinal projections to the CTM motor nucleus, originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum.

Electrophysiological appraisal of relative segmental motoneurone pool excitability in flexor and extensor.

PubMed Central

Fisher, M A

1978-01-01

F responses recorded from flexor and extensor muscles were analysed in 18 normal subjects and in 16 patients with motor system abnormalities. The prominence of the F responses was evaluated quantitatively by determining the persistence--that is, the fraction of measurable F responses which actually occur after a series of supramaximal stimuli--and average amplitude of the F responses. In the normal resting state, the data are consistent with the hypothesis that the "central excitatory states" of motoneurones is greater in the antigravity muscles than in those muscles not stretched by gravity. This pattern was disrupted in eight of the 16 patients with motor system abnormalities caused by central nervous system lesions. These changes reflect a clinically testable aspect of the pathophysiology of certain motor system disorders. PMID:690640

Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic

PubMed Central

Bhumbra, Gardave S.

2018-01-01

Spinal motoneurones (Mns) constitute the final output for the execution of motor tasks. In addition to innervating muscles, Mns project excitatory collateral connections to Renshaw cells (RCs) and other Mns, but the latter have received little attention. We show that Mns receive strong synaptic input from other Mns throughout development and into maturity, with fast-type Mns systematically receiving greater recurrent excitation than slow-type Mns. Optical recordings show that activation of Mns in one spinal segment can propagate to adjacent segments even in the presence of intact recurrent inhibition. While it is known that transmission at the neuromuscular junction is purely cholinergic and RCs are excited through both acetylcholine and glutamate receptors, here we show that neurotransmission between Mns is purely glutamatergic, indicating that synaptic transmission systems are differentiated at different postsynaptic targets of Mns. PMID:29538375

Notochord alters the permissiveness of myotome for pathfinding by an identified motoneuron in embryonic zebrafish.

PubMed

Beattie, C E; Eisen, J S

1997-02-01

During zebrafish development, identified motoneurons innervate cell-specific regions of each trunk myotome. One motoneuron, CaP, extends an axon along the medial surface of the ventral myotome. To learn how this pathway is established during development, the CaP axon was used as an assay to ask whether other regions of the myotome were permissive for normal CaP pathfinding. Native myotomes were replaced with donor myotomes in normal or reversed dorsoventral orientations and CaP pathfinding was assayed. Ventral myotomes were permissive for CaP axons, even when they were taken from older embryos, suggesting that the CaP pathway remained present on ventral myotome throughout development. Dorsal myotomes from young embryos were also permissive for CaP axons, however, older dorsal myotomes were non-permissive, showing that permissiveness of dorsal myotome for normal CaP pathfinding diminished over time. This process appears to depend on signals from the embryo, since dorsal myotomes matured in vitro remained permissive for CaP axons. Genetic mosaics between wild-type and floating head mutant embryos revealed notochord involvement in dorsal myotome change of permissiveness. Dorsal and ventral myotomes from both younger and older floating head mutant embryos were permissive for CaP axons. These data suggest that initially both dorsal and ventral myotomes are permissive for CaP axons but as development proceeds, there is a notochord-dependent decrease in permissiveness of dorsal myotome for CaP axonal outgrowth. This change participates in restricting the CaP pathway to the ventral myotome and thus to neuromuscular specificity.

Cellular and synaptic effect of substance P on neonatal phrenic motoneurons.

PubMed

Ptak, K; Konrad, M; Di Pasquale, E; Tell, F; Hilaire, G; Monteau, R

2000-01-01

Experiments were carried out on the in vitro brainstem-spinal cord preparation of the newborn rat to analyse the effects of substance P (SP) on phrenic motoneuron (PMN) activity. In current-clamp mode, SP significantly depolarized PMNs, increased their input resistance, decreased the rheobase current and shifted the firing frequency-intensity relationships leftwards, but did not affect spike frequency adaptation or single spike configuration. The neurokinin receptor agonist NK1 had SP-mimetic effects, whereas the NK3 and NK2 receptor agonists were less effective and ineffective, respectively. In a tetrodotoxin-containing aCSF, only SP or the NK1 receptor agonist were still active. No depolarization was observed when the NK1 receptor agonist was applied in the presence of muscarine. In voltage-clamp mode, SP or the NK1 receptor agonist produced an inward current (ISP) which was not significantly reduced by extracellular application of tetraethylammonium, Co2+, 4-aminopyridine or Cs+. In aCSF containing tetrodotoxin, Co2+ and Cs+, ISP was blocked by muscarine. No PMN displayed any M-type potassium current but only a current showing no voltage sensitivity over the range -100 to 0 mV, reversing near the expected EK +, hence consistent with a leak current. SP application to the spinal cord only (using a partitioned chamber) significantly increased the phrenic activity. Pretreatment with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) decreased the C4 discharge duration and blocked the effect of SP, thus exhibiting an NMDA potentiation by SP. In conclusion, SP modulates postsynaptically the response of phrenic motoneurons to the inspiratory drive through the reduction of a leak conductance and the potentiation of the NMDA component of the synaptic input.

Amyotrophic lateral sclerosis immunoglobulins increase intracellular calcium in a motoneuron cell line.

PubMed

Colom, L V; Alexianu, M E; Mosier, D R; Smith, R G; Appel, S H

1997-08-01

A hybrid motoneuron cell line (VSC4.1) was used as a model system to study the relationship between alterations in intracellular calcium and subsequent cell death induced by immunoglobulin fractions purified from sera of patients with ALS. Using fluo-3 fluorescence imaging, immunoglobulins from 8 of 10 patients with ALS were found to induce transient increases in intracellular calcium ([Ca2+]i) in differentiated VSC4.1 cells. These transient [Ca2+]i increases required extracellular calcium entry through voltage-gated calcium channels sensitive to synthetic FTX and to high concentrations (>1 microM) of omega-agatoxin IVa. The incidence of transient [Ca2+]i increases induced by ALS immunoglobulins correlated with the extent of cytotoxicity induced by the same ALS immunoglobulins in parallel cultures of VSC4.1 cells. Furthermore, manipulations which blocked transient [Ca2+]i increases (addition of synthetic FTX or omega-agatoxin IVa) also inhibited the cytotoxic effects of ALS immunoglobulins. No transient calcium increases were observed in VSC4.1 cells following addition of immunoglobulins from 7 neurologic disease control patients. However, transient [Ca2+]i increases were observed following addition of immunoglobulins from 4 of 5 patients with myasthenia gravis (MG). The [Ca2+]i changes induced by MG immunoglobulins were not blocked by s-FTX, suggesting that they result from a different mechanism than those induced by ALS immunoglobulins. These results suggest that immunoglobulins from patients with ALS can induce transient increases in intracellular calcium in a motoneuron cell line, which may represent early events in the cascade of processes leading to injury and death of susceptible cells.

miR-7-1 POTENTIATED ESTROGEN RECEPTOR AGONISTS FOR FUNCTIONAL NEUROPROTECTION IN VSC4.1 MOTONEURONS

PubMed Central

CHAKRABARTI, M.; BANIK, N. L.; RAY, S. K.

2013-01-01

Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI) insulted VSC4.1 motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using miRDB indicated that miR-7-1 could inhibit expression of L-type Ca2+ channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca2+/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future to attenuate apoptosis of motoneurons in SCI. PMID

MiR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons.

PubMed

Chakrabarti, M; Banik, N L; Ray, S K

2014-01-03

Protection of motoneurons is an important goal in the treatment of spinal cord injury (SCI). We tested whether neuroprotective microRNAs (miRs) like miR-206, miR-17, miR-21, miR-7-1, and miR-106a could enhance efficacy of estrogen receptor (ER) agonists such as 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT, ERα agonist), Way200070 (WAY, ERβ agonist), and estrogen (EST, ERα and ERβ agonist) in preventing apoptosis in the calcium ionophore (CI)-insulted ventral spinal cord 4.1 (VSC4.1) motoneurons. We determined that 200 nM CI induced 70% cell death. Treatment with 50 nM PPT, 100 nM WAY, and 150 nM EST induced overexpression of ERα, ERβ, and both receptors, respectively, at mRNA and protein levels. Treatment with ER agonists significantly upregulated miR-206, miR-17, and miR-7-1 in the CI-insulted VSC4.1 motoneurons. Transfection with miR-206, miR-17, or miR-7-1 mimic potentiated WAY or EST to inhibit apoptosis in the CI-insulted VSC4.1 motoneurons. Overexpression of miR-7-1 maximally increased efficacy of WAY and EST for down regulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2. A search using microRNA database (miRDB) indicated that miR-7-1 could inhibit the expression of L-type Ca(2+) channel protein alpha 1C (CPα1C). miR-7-1 overexpression and WAY or EST treatment down regulated CPα1C but upregulated p-Akt to trigger cell survival signaling. The same therapeutic strategy increased expression of the Ca(2+)/calmodulin-dependent protein kinase II beta (CaMKIIβ) and the phosphorylated cAMP response element binding protein (p-CREB) so as to promote Bcl-2 transcription. Whole cell membrane potential and mitochondrial membrane potential studies indicated that miR-7-1 highly potentiated EST to preserve functionality in the CI-insulted VSC4.1 motoneurons. In conclusion, our data indicated that miR-7-1 most significantly potentiated efficacy of EST for functional neuroprotection and this therapeutic strategy could be used in the future

Soma size and Cav1.3 channel expression in vulnerable and resistant motoneuron populations of the SOD1G93A mouse model of ALS

PubMed Central

Shoenfeld, Liza; Westenbroek, Ruth E.; Fisher, Erika; Quinlan, Katharina A.; Tysseling, Vicki M.; Powers, Randall K.; Heckman, Charles J.; Binder, Marc D.

2014-01-01

Abstract Although the loss of motoneurons is an undisputed feature of amyotrophic lateral sclerosis (ALS) in man and in its animal models (SOD1 mutant mice), how the disease affects the size and excitability of motoneurons prior to their degeneration is not well understood. This study was designed to test the hypothesis that motoneurons in mutant SOD1G93A mice exhibit an enlargement of soma size (i.e., cross‐sectional area) and an increase in Cav1.3 channel expression at postnatal day 30, well before the manifestation of physiological symptoms that typically occur at p90 (Chiu et al. 1995). We made measurements of spinal and hypoglossal motoneurons vulnerable to degeneration, as well as motoneurons in the oculomotor nucleus that are resistant to degeneration. Overall, we found that the somata of motoneurons in male SOD1G93A mutants were larger than those in wild‐type transgenic males. When females were included in the two groups, significance was lost. Expression levels of the Cav1.3 channels were not differentiated by genotype, sex, or any interaction of the two. These results raise the intriguing possibility of an interaction between male sex steroid hormones and the SOD1 mutation in the etiopathogenesis of ALS. PMID:25107988

[REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

PubMed

Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

2016-02-01

A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

On a method to detect long-latency excitations and inhibitions of single hand muscle motoneurons in man.

PubMed

Awiszus, F; Feistner, H; Schäfer, S S

1991-01-01

The peri-stimulus-time histogram (PSTH) analysis of stimulus-related neuronal spike train data is usually regarded as a method to detect stimulus-induced excitations or inhibitions. However, for a fairly regularly discharging neuron such as the human alpha-motoneuron, long-latency modulations of a PSTH are difficult to interpret as PSTH modulations can also occur as a consequence of a modulated neuronal autocorrelation. The experiments reported here were made (i) to investigate the extent to which a PSTH of a human hand-muscle motoneuron may be contaminated by features of the autocorrelation and (ii) to develop methods that display the motoneuronal excitations and inhibitions without such contamination. Responses of 29 single motor units to electrical ulnar nerve stimulation below motor threshold were investigated in the first dorsal interosseous muscle of three healthy volunteers using an experimental protocol capable of demonstrating the presence of autocorrelative modulations in the neuronal response. It was found for all units that the PSTH as well as the cumulative sum (CUSUM) derived from these responses were severely affected by the presence of autocorrelative features. On the other hand, calculating the CUSUM in a slightly modified form yielded--for all units investigated--a neuronal output feature sensitive only to motoneuronal excitations and inhibitions induced by the afferent volley. The price that has to be paid to arrive at such a modified CUSUM (mCUSUM) was a high computational effort prohibiting the on-line availability of this output feature during the experiment. It was found, however, that an interspike interval superposition plot (IISP)--easily obtainable during the experiment--is also free of autocorrelative features.(ABSTRACT TRUNCATED AT 250 WORDS)

Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling.

PubMed

Madji Hounoum, Blandine; Mavel, Sylvie; Coque, Emmanuelle; Patin, Franck; Vourc'h, Patrick; Marouillat, Sylviane; Nadal-Desbarats, Lydie; Emond, Patrick; Corcia, Philippe; Andres, Christian R; Raoul, Cédric; Blasco, Hélène

2017-04-01

The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605. © 2017 Wiley Periodicals, Inc.

CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency.

PubMed

Brockmann, Sarah J; Freischmidt, Axel; Oeckl, Patrick; Müller, Kathrin; Ponna, Srinivas K; Helferich, Anika M; Paone, Christoph; Reinders, Jörg; Kojer, Kerstin; Orth, Michael; Jokela, Manu; Auranen, Mari; Udd, Bjarne; Hermann, Andreas; Danzer, Karin M; Lichtner, Peter; Walther, Paul; Ludolph, Albert C; Andersen, Peter M; Otto, Markus; Kursula, Petri; Just, Steffen; Weishaupt, Jochen H

2018-02-15

Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p.R15L and p.G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p.P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p.R15L and p.G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p.R15L, but not of CHCHD10 p.G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p.G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p.P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuromuscular Junction Formation between Human Stem cell-derived Motoneurons and Human Skeletal Muscle in a Defined System

PubMed Central

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman; Hickman, James

2011-01-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time lapse recordings and their subsequent quenching by D-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. PMID:21944471

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

2011-12-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neuromuscular plasticity in the locust after permanent removal of an excitatory motoneuron of the extensor tibiae muscle.

PubMed

Büschges, A; Djokaj, S; Bässler, D; Bässler, U; Rathmayer, W

2000-01-01

The capacity of the larval insect nervous system to compensate for the permanent loss of one of the two excitatory motoneurons innervating a leg muscle was investigated in the locust (Locusta migratoria). In the fourth instar, the fast extensor tibiae (FETi) motoneuron in the mesothoracic ganglion was permanently removed by photoinactivation with a helium-cadmium laser. Subsequently, the animals were allowed to develop into adulthood. When experimental animals were tested as adults after final ecdysis, fast-contracting fibers in the most proximal region of the corresponding extensor muscle, which are normally predominantly innervated by FETi only, uniformly responded to activity of the slow extensor tibiae (SETi) neuron. In adult operated animals, single pulses to SETi elicited large junctional responses in the fibers which resulted in twitch contractions of these fibers similar to the responses to FETi activity in control animals. The total number of muscle fibers, their properties as histochemically determined contractional types (fast and slow), and their distribution were not affected by photoinactivation of FETi. Possible mechanisms enabling the larval neuromuscular system to compensate for the loss of FETi through functionally similar innervation by a different motoneuron, i.e. SETi, are discussed. Copyright 2000 John Wiley & Sons, Inc.

Thresholds of cortical activation of muscle spindles and α motoneurones of the baboon's hand

PubMed Central

Koeze, T. H.; Phillips, C. G.; Sheridan, J. D.

1968-01-01

1. Much current thinking about voluntary movement assumes that the segmental γ loops can function as a servomechanism operated by the brain. However, the α motoneurones of the baboon's hand receive a powerful monosynaptic (CM) projection from the precentral gyrus. If servo-driving from the same cortical area is to be possible, it must project independently to the fusimotor neurones and have sufficient power to increase the afferent signalling from the muscle spindles. The cortical thresholds for contraction of m. extensor digitorum communis and for acceleration of the discharges of its muscle spindles have therefore been compared. 2. Significant results in this context require that the spindles studied be coupled in parallel with the responding extrafusal muscle fibres. Many spindles were not unloaded by the submaximal contractions evoked by cortical stimulation, although all so tested were unloaded by maximal motor nerve twitches. Reasons are given for thinking that such apparent lack of parallel coupling is an artifact of complex intramuscular anatomy and limitation of shortening by `isometric' myography. 3. A brief burst of corticospinal volleys at 500/sec, which is specially effective in exciting α motoneurones over the CM projection, failed to excite spindle afferents at or below the threshold for a cortical `twitch'. 4. In a few epileptiform discharges, bursts of spindle acceleration occurred independently of the clonic contractions. A relatively direct and independent cortico-fusimotor (CF) projection may therefore exist. 5. Prolonged near-threshold stimulation at 50-100/sec, which allows time for temporal summation in the less direct projections (e.g. cortico-interneuronal, cortico-rubro-spinal) and does not cause frequency-potentiation at CM synapses, gives abundant evidence of independent α and fusimotor projections, whose actions hardly outlast the stimulation period. 6. Although independent CF projections would permit servo-driving in natural

The development of cortico-motoneuronal projections investigated using magnetic brain stimulation in the infant macaque.

PubMed

Flament, D; Hall, E J; Lemon, R N

1992-02-01

1. The effects of magnetic brain stimulation on electromyographic (EMG) activity recorded from arm and hand muscles have been investigated in five infant and six adult macaque monkeys under ketamine sedation. 2. In the adults, brief, short-latency EMG responses could be readily evoked with magnetic stimuli of 40-50% of the maximum stimulator output (1.5 T). 3. In a cross-sectional study of five infant macaques, it was difficult to evoke EMG responses in young infants (less than 5 months old). Clear short-latency responses were first evoked in an animal 5.75 months old. This change was accompanied by an increase in the probability of occurrence of the responses. 4. In a longitudinal study of two infant monkeys over a period ranging from 2.5 to 14.5 months of age we found that clear short-latency responses were first evoked at 4 and at 5.5 months, respectively. In both animals there was a steady fall in response threshold which reached the adult range at 6.5 and 8 months, respectively. EMG responses in animals older than 8 months were indistinguishable from those in adults. 5. In the longitudinal study we also noted that the latency of EMG responses to magnetic brain stimulation declined with age. Since there were no comparable changes in the peripheral conduction time in these animals, we attribute this result to a decrease in central conduction time. 6. Parallel behavioural observations of the natural behaviour of the same animals within a colony indicated that mature precision movements of the fingers were not used until 5-6 months of age. 7. In two adult monkeys, the latency of EMG responses evoked in the extensor digitorum and first dorsal interosseous muscles by direct stimulation of the corticospinal tract, via electrodes implanted in the medullary pyramids, was found to be 0.7-1.7 ms shorter than that of responses evoked by magnetic stimuli. It is argued that at least the earliest component of these latter responses is conducted over the cortico-motoneuronal

Doublecortin is expressed in trigeminal motoneurons that innervate the velar musculature of lampreys: considerations on the evolution and development of the trigeminal system.

PubMed

Barreiro-Iglesias, Antón; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Rodicio, María Celina

2011-01-01

Studies in lampreys have revealed interesting aspects of the evolution of the trigeminal system and the jaw. In the present study, we found a marker that distinguishes subpopulations of trigeminal motoneurons innervating two different kinds of oropharyngeal muscles. Immunofluorescence with an antibody against doublecortin (DCX; a neuron-specific phosphoprotein) enabled identification of the trigeminal motoneurons that innervate the velar musculature of larval and recently transformed sea lampreys. DCX-immunoreactive (-ir) motoneurons were observed in the rostro-lateral part of the trigeminal motor nucleus of these animals, but not in lampreys 1 month or more after metamorphosis. Combined double DCX/tubulin and serotonin/tubulin immunofluorescence and tract-tracing experiments with neurobiotin (NB) were also performed in larvae for further characterization of this system. Rich innervation by DCX-ir fibers was observed on the muscle fibers of the velum but not on the upper lip or lower lip muscles, which were innervated by tubulin-ir/DCX-negative fibers. No double-labelled DCX-ir motoneurons were observed in experiments in which the tracer NB was applied to the upper lip. Innervation of velar muscles by serotonergic fibers is also reported. The present results indicate that development of the trigeminal motoneurons innervating the velum differs from that of the trigeminal motoneurons innervating the lips, which is probably related to the dramatic regression of the velum during metamorphosis. The absence of data on a similar subsystem in the trigeminal motor nucleus of gnathostomes suggests that they may be lamprey-specific motoneurons. These results provide support for the "heterotopic theory" of jaw evolution and are inconsistent with the theories of a velar origin for the gnathostome jaw. © 2011 Wiley Periodicals, Inc.

Rapid activity-dependent modulation of the intrinsic excitability through up-regulation of KCNQ/Kv7 channel function in neonatal spinal motoneurons.

PubMed

Lombardo, Joseph; Sun, Jianli; Harrington, Melissa A

2018-01-01

Activity-dependent changes in the properties of the motor system underlie the necessary adjustments in its responsiveness on the basis of the environmental and developmental demands of the organism. Although plastic changes in the properties of the spinal cord have historically been neglected because of the archaic belief that the spinal cord is constituted by a hardwired network that simply relays information to muscles, plenty of evidence has been accumulated showing that synapses impinging on spinal motoneurons undergo short- and long-term plasticity. In the brain, brief changes in the activity level of the network have been shown to be paralleled by changes in the intrinsic excitability of the neurons and are suggested to either reinforce or stabilize the changes at the synaptic level. However, rapid activity-dependent changes in the intrinsic properties of spinal motoneurons have never been reported. In this study, we show that in neonatal mice the intrinsic excitability of spinal motoneurons is depressed after relatively brief but sustained changes in the spinal cord network activity. Using electrophysiological techniques together with specific pharmacological blockers of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the intrinsic excitability of spinal motoneurons. This action results from an increased M-current, the product of the activation of KCNQ/Kv7 channels, which leads to a hyperpolarization of the resting membrane potential and a decrease in the input resistance of spinal motoneurons. Computer simulations showed that specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of the intrinsic excitability of spinal motoneurons as observed experimentally. These results indicate that KCNQ/Kv7 channels play a fundamental role in the activity-dependent modulation of the excitability of spinal motoneurons.

Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

PubMed Central

Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

2014-01-01

Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

Laser ablation of Drosophila embryonic motoneurons causes ectopic innervation of target muscle fibers

NASA Technical Reports Server (NTRS)

Chang, T. N.; Keshishian, H.

1996-01-01

We have tested the effects of neuromuscular denervation in Drosophila by laser-ablating the RP motoneurons in intact embryos before synaptogenesis. We examined the consequences of this ablation on local synaptic connectivity in both 1st and 3rd instar larvae. We find that the partial or complete loss of native innervation correlates with the appearance of alternate inputs from neighboring motor endings and axons. These collateral inputs are found at ectopic sites on the denervated target muscle fibers. The foreign motor endings are electrophysiologically functional and are observed on the denervated muscle fibers by the 1st instar larval stage. Our data are consistent with the existence of a local signal from the target environment, which is regulated by innervation and influences synaptic connectivity. Our results show that, despite the stereotypy of Drosophila neuromuscular connections, denervation can induce local changes in connectivity in wild-type Drosophila, suggesting that mechanisms of synaptic plasticity may also be involved in normal Drosophila neuromuscular development.

Giant multimodal heart motoneurons of Achatina fulica: a new cardioregulatory input in pulmonates.

PubMed

Zhuravlev, V; Bugaj, V; Kodirov, S; Safonova, T; Staruschenko, A

2001-08-01

The regulation of the heartbeat by the two largest neurons, d-VLN and d-RPLN, on the dorsal surface of visceral and right parietal ganglia of Giant African snail, Achatina fulica, was examined. Using the new method of animal preparation, for the first time, discrete biphasic inhibitory-excitatory junction potentials (I-EJPs) in the heart and several muscles of the visceral sac were recorded. The duration of hyperpolarizing phase (H-phase) of biphasic I-EJPs was 269+/-5.6 ms (n=5), which is 2-3 times less than that of the cholinergic inhibitory JPs (682+/-68.5 ms, n=5). The H-phase of I-EJPs was not altered by the application of atropine, picrotoxine, succinylcholinchloride, D-tubocurarine and tetraethylammonium or substitution of Cl(-) ions. Even the low-frequency neuronal discharges (1-2 imp/s) evoked significant facilitation and potentiation of the H-phase. Between the multimodal neurons d-VLN/d-RPLN and mantle or visceral organs there is evidence of direct synaptic connections. These neurons were found to have no axonal branches in the intestinal nerve as once suspected but reach the heart through several other nerves. New giant heart motoneurons do not interact with previously identified cardioregulatory neurons.

Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

PubMed Central

Smith, Andrew C.; Mummidisetty, Chaithanya K.

2015-01-01

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs. PMID:25609110

HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration.

PubMed

La Padula, Veronica; Staszewski, Ori; Nestel, Sigrun; Busch, Hauke; Boerries, Melanie; Roussa, Eleni; Prinz, Marco; Krieglstein, Kerstin

2016-12-01

The human small heat shock proteins (HSPBs) form a family of molecular chaperones comprising ten members (HSPB1-HSPB10), whose functions span from protein quality control to cytoskeletal dynamics and cell death control. Mutations in HSPBs can lead to human disease and particularly point mutations in HSPB1 and HSPB8 are known to lead to peripheral neuropathies. Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C). Until now, HSPB3 protein localization and function in motoneurons (MNs) have not yet been characterized. Therefore, we studied the endogenous HSPB3 protein distribution in the spinal cords of chicken and mouse embryos and in the postnatal nervous system (central and peripheral) of chicken, mouse and human. We further investigated the impact of wild-type and mutated HSPB3 on MN cell death via overexpressing these genes in ovo in an avian model of MN degeneration, the limb-bud removal. Altogether, our findings represent a first step for a better understanding of the cellular and molecular mechanisms leading to dHMN2C. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

PubMed Central

Sivertsen, Magne S.; Glover, Joel C.

2014-01-01

Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively. In nonlesioned preparations, responses in both ipsi- and contralateral MNs followed individual stimuli in stimulus trains nearly one-to-one (with few failures). After unilateral hemisection at C1 on the same side as the stimulation, responses had substantially smaller magnitudes and longer latencies and no longer followed individual stimuli. After unilateral hemisection at C1 on the side opposite to the stimulation, the responses were also smaller, but their latencies were not affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs, one uncrossed and the other crossed, of which the uncrossed pathway transmits more faithfully and appears to be more direct. PMID:24944221

Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death

PubMed Central

Jablonka, Sibylle; Holtmann, Bettina; Meister, Gunter; Bandilla, Michael; Rossoll, Wilfried; Fischer, Utz; Sendtner, Michael

2002-01-01

Neuronal degeneration in spinal muscular atrophy is caused by reduced expression of the survival motor neuron (SMN) protein. SMN and the tightly interacting Gemin2 form part of a macromolecular complex (SMN complex) that mediates assembly of spliceosomal small nuclear ribonucleoproteins (U snRNPs). We used mouse genetics to investigate the function of this complex in motoneuron maintenance. Reduced Smn/Gemin2 protein levels lead to disturbed U snRNP assembly as indicated by reduced nuclear accumulation of Sm proteins. This finding correlates with enhanced motoneuron degeneration in Gemin2+/−/Smn+/− mice. Our data provide in vivo evidence that impaired production of U snRNPs contributes to motoneuron degeneration. PMID:12091709

The volatile anesthetic methoxyflurane protects motoneurons against excitotoxicity in an in vitro model of rat spinal cord injury.

PubMed

Shabbir, A; Bianchetti, E; Nistri, A

2015-01-29

Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons. The present investigation examined whether the volatile general anesthetic methoxyflurane might protect spinal locomotor networks from kainate-evoked excitotoxicity using an in vitro rat spinal cord preparation as a model. The protocols involved 1h excitotoxic stimulation on day 1 followed by electrophysiological and immunohistochemical testing on day 2. A single administration of methoxyflurane applied together with kainate (1h), or 30 or even 60 min later prevented any depression of spinal reflexes, loss of motoneuron excitability, and histological damage. Methoxyflurane per se temporarily decreased synaptic transmission and motoneuron excitability, effects readily reversible on washout. Spinal locomotor activity recorded as alternating electrical discharges from lumbar motor pools was fully preserved on the second day after application of methoxyflurane together with (or after) kainate. These data suggest that a volatile general anesthetic could provide strong electrophysiological and histological neuroprotection that enabled expression of locomotor network activity 1 day after the excitotoxic challenge. It is hypothesized that the benefits of early neurosurgery for acute spinal cord injury (SCI) might be enhanced if, in addition to injury decompression and stabilization, the protective role of general anesthesia is exploited. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

PubMed Central

Titus-Mitchell, Haley E.; Bullinger, Katie L.; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C.

2011-01-01

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons. PMID:21832035

Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans.

PubMed

Marchand-Pauvert, V; Nicolas, G; Pierrot-Deseilligny, E

2000-05-15

Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level. Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents. Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s-1). A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side. It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat

Motoneuron regeneration accuracy and recovery of gait after femoral nerve injuries in rats.

PubMed

Kruspe, M; Thieme, H; Guntinas-Lichius, O; Irintchev, A

2014-11-07

The rat femoral nerve is a valuable model allowing studies on specificity of motor axon regeneration. Despite common use of this model, the functional consequences of femoral nerve lesions and their relationship to precision of axonal regeneration have not been evaluated. Here we assessed gait recovery after femoral nerve injuries of varying severity in adult female Wistar rats using a video-based approach, single-frame motion analysis (SFMA). After nerve crush, recovery was complete at 4 weeks after injury (99% of maximum 100% as estimated by a recovery index). Functional restoration after nerve section/suture was much slower and incomplete (84%) even 20 weeks post-surgery. A 5-mm gap between the distal and proximal nerve stumps additionally delayed recovery and worsened the outcome (68% recovery). As assessed by retrograde labeling in the same rats at 20 weeks after injury, the anatomical outcome was also dependent on lesion severity. After nerve crush, 97% of the femoral motoneurons (MNs) had axons correctly projecting only into the distal quadriceps branch of the femoral nerve. The percentage of correctly projecting MNs was only 55% and 15% after nerve suture and gap repair, respectively. As indicated by regression analyses, better functional recovery was associated with higher numbers of correctly projecting MNs and, unexpectedly, lower numbers of MNs projecting to both muscle and skin. The data show that type of nerve injury and repair profoundly influence selectivity of motor reinnervation and, in parallel, functional outcome. The results also suggest that MNs' projection patterns may influence their contribution to muscle performance. In addition to the experiments described above, we performed repeated measurements and statistical analyses to validate the SFMA. The results revealed high accuracy and reproducibility of the SFMA measurements. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Location of the motoneurons of the mylohyoid muscle in the rat. A fluorescence and Nissl study.

PubMed

Badran, Darwish H; Al-Hadidi, Maher T; Ramadan, Hassan N; Abu-Ghaida, Jamal H

2005-01-01

To locate the neuronal motor cells of the mylohyoid muscle and discuss their topographical organization. The present study was conducted at the Department of Anatomy and Histology, Faculty of Medicine, University of Jordan, Amman, Jordan between 2002 and 2003. The mylohyoid muscle in 15 albino rats was injected with 15 mliter of a retrogradely transported fluorescent material DAPI-Pr. After a survival period of 48 hours, animals were sacrificed, fixed in situ and brains harvested. The caudorostral transverse sections of the hindbrains were examined under the fluorescence microscope to detect the fluorescing cells, which were immediately photographed. Sections containing the labeled cells were charted, stained with 1% thionine and photographs obtained through light and fluorescence microscopes at different magnifications. The place and shape of all labeled cells were singled out by asset of their charted referring photographs of hindbrain sections, which display the entire motor trigeminal nucleus. The results showed that the fluorescent cell increase was found to occupy the rostromedial part of the ipsilateral motor trigeminal nucleus. The nucleus was large at its caudal third; the labeled cells are mainly those of the medial "subgroup". These cells are rationally distinct and lie alongside the internal loop of the facial nerve. At the middle third, most of the medial "subgroup" was found labeled. At its middle, the nucleus found was well developed, attained an appreciable size and its medial "subgroup" was somewhat distinct. Whereas, at the rostral third, the nucleus was larger, the medial group was more distinct and all cells were labeled. The medial cellular mass of the nucleus showed reduced labeled cells at the rostral end. This study demonstrates that the rostromedial part of the motor trigeminal nucleus represents the absolute territorial domain of the mylohyoid muscle motoneurons.

Presynaptic modulation of tonic and respiratory inputs to cardiovagal motoneurons by substance P.

PubMed

Hou, Lili; Tang, Hongtai; Chen, Yonghua; Wang, Lin; Zhou, Xujiao; Rong, Weifang; Wang, Jijiang

2009-08-11

Substance P (SP) has been implicated in vagal control of heart rate and cardiac functions, but the mechanisms of SP actions on cardiac vagal activity remain obscure. The present study has investigated the effects of SP on the synaptic inputs of preganglionic cardiovagal motoneurons (CVNs) in brainstem slices of neonatal rat. Whole-cell voltage-clamp recordings were performed on retrogradely labeled CVNs in the nucleus ambiguus. The results show that in thin slices (400 microm thickness) without respiratory-like rhythm, globally applied SP (1 microM) significantly enhanced both the GABAergic and the glycinergic inputs, but had no effect on the glutamatergic inputs, of CVNs. Since inspiratory-related augmentation of the inhibitory inputs of CVNs in individual respiratory cycles is known to play an important role in the genesis of respiratory sinus arrhythmia, the effects of SP on the inhibitory inputs of CVNs were further examined in thick slices (500-800 microm thickness) with respiratory-like rhythm, and SP (1 microM) was focally applied to the CVNs under patch-clamp recording. Focally applied SP caused frequency increases of the GABAergic and the glycinergic inputs both during inspiratory bursts and during inspiratory intervals. However, the inspiratory-related augmentation of the GABAergic and the glycinergic inputs of CVNs, measured by the frequency increases during inspiratory bursts in percentage of the frequency during inspiratory intervals, was significantly decreased by SP. These results suggest that SP inhibits CVNs via enhancement of their inhibitory synaptic inputs, and SP diminishes the respiratory-related fluctuation of cardiac vagal activity in individual respiratory cycles. These results also indicate that SP may play a role in altering the vagal control of the heart in some cardiovascular diseases such as myocardial ischemia and hypertension, since these diseases are characterized by weakened cardiac vagal tone and heart rate variability, and have

Changes in the estimated time course of the motoneuron afterhyperpolarization induced by tendon vibration.

PubMed

MacDonell, Christopher W; Ivanova, Tanya D; Garland, S Jayne

2010-12-01

Group Ia afferents are activated vigorously with high-frequency tendon vibration and provide excitatory input to the agonist muscle and inhibitory input to the antagonist muscle group via inhibitory interneurons. The purpose of this experiment was to determine whether the afterhyperpolarization (AHP) time course in humans is altered in response to tendon vibration. The AHP time course is estimated using the interval death rate (IDR) analysis, a transform of the motor unit action potential train. Single motor units from tibialis anterior (TA) were recorded as subjects held low force dorsiflexor contractions for 600 s with and without vibration. The vibratory stimulus was superimposed on the low force contraction either to the tendon of the TA or the antagonist Achilles tendon. During TA tendon vibration, the time course of the AHP, as expressed by its time constant (τ), decreased from 35.5 ms in the previbration control condition to 31.3 ms during the vibration (P = 0.003) and returned to 36.3 ms after the vibration was removed (P = 0.002). The AHP τ during vibration of the antagonist Achilles tendon (38.6 ms) was greater than the previbration control condition (33.6 ms; P = 0.001). It is speculated that the reduction in AHP time constant with TA vibration may have resulted alone or in combination with a modulation of motoneuron gain, an alteration of persistent inward currents and/or the restructuring of synaptic noise. A decrease in firing probability, possibly reflecting Ia reciprocal inhibition, may have been responsible for the larger AHP time constant.

THE REGENERATIVE CYCLE OF MOTONEURONS, WITH SPECIAL REFERENCE TO PHOSPHATASE ACTIVITY.

PubMed

Bodian, D; Mellors, R C

1945-05-01

1. The regenerative cycle of motoneurons after axon amputation is described, and an attempt made to correlate morphological and chemical events in cell bodies with the growth requirements of regenerating axons. 2. The "normal" pattern of Nissl material in the cell is considered to be the resultant of a steady state in cytoplasmic nucleoprotein. Chromatol is then interpreted as a shift of the balance of nucleoprotein turnover in fa of degradation. The rapid early depletion of Nissl substance in chromatolysis is ascribed to the increased growth requirements created by the active early sprouting of the regenerating axon. Acid phosphatase activity begins to increase above normal levels during this period in the region of nucleopro degradation. 3. The recovery period of chromatolysis due to axon section coincide in time with the phase of gradual lengthening of the regenerating axon, and is thought to represent a gradual restoration of the balance of nucleoprotein degradation and synthesis. During this period acid phosphatase activity is at its height in the region of transformation of Nissl substance, later declines to normal levels when the original pattern of Nissl bodie is restored. 4. The transformation of cytoplasmic nucleoprotein which occurs in chromatolysis after axon section, with the probable liberation (46), and depletion (44), of nucleotides, associated with acid phosphatase activity, suggests the hypothesis that liberated nucleotides or nucleotide compounds may pass down the axon in which they take part in enzymatic activity associated with growth and organization of the newly formed axon. This type of activity would not be incompatible with the ideas previously expressed (30, 81) of a continual function of Nissl substance in maintaining the integrity of the large volume of cytoplasm represented by the axon, as well perhaps as the associated myelin sheath.

Synaptology of the direct projections from the nucleus of the solitary tract to pharyngeal motoneurons in the nucleus ambiguus of the rat.

PubMed

Hayakawa, T; Zheng, J Q; Seki, M; Yajima, Y

1998-04-13

During the pharyngeal phase of the swallowing reflex, the nucleus of the solitary tract (NTS) receives peripheral inputs from the pharynx by means of the glossopharyngeal ganglion and is the location of premotor neurons for the pharyngeal (PH) motoneurons. The semicompact formation of the nucleus ambiguus (AmS) is composed of small and medium-sized neurons that do not project to the pharynx, and large PH motoneurons. We investigated whether the neurons in the NTS projected directly to the PH motoneurons or to the other kinds of neurons in the AmS by using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) injections into the pharyngeal muscles of male Sprague-Dawley rats, many nerve terminals anterogradely labeled with WGA-HRP were found to contact PH motoneurons retrogradely labeled with CT-HRP. Most of the labeled axodendritic terminals (63%) contained pleomorphic vesicles with symmetric synaptic contacts (Gray's type II), and the remaining ones contained round vesicles with asymmetric synaptic contacts (Gray's type I). About 14% of the axosomatic terminals on PH motoneuron in a sectional plane were anterogradely labeled, and about 70% of the labeled axosomatic terminals were Gray's type II. Observations of serial ultrathin sections revealed that both the small and the medium-sized neurons received only a few labeled axosomatic terminals that were exclusively Gray's type I. These results indicate that the NTS neurons may send mainly inhibitory as well as a few excitatory inputs directly to the PH motoneurons in the AmS.

Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells due to interferon-gamma exposure

PubMed Central

Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A.; Krause, James S.; Banik, Naren L.

2014-01-01

Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. In order to examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis related proteases (caspase-3 and −12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. PMID:24188094

Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells because of interferon-gamma exposure.

PubMed

Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Krause, James S; Banik, Naren L

2014-03-01

Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. To examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis-related proteases (caspase-3 and -12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. © 2013 International Society for Neurochemistry.

Topochemical differences in the amount of RNA in the motoneurons of the spinal chord in hypoxia and hypokinesia

NASA Technical Reports Server (NTRS)

Brumberg, V. A.; Gazenko, O. G.; Demin, N. N.; Malkin, V. B.; Pevzner, L. Z.

1980-01-01

Reactions to hypoxia and hypoknesia were compared by measuring charges in the amount of ribonucleic acid (RNA) in the cytoplasm of neurons of the intumescentia cervicalis and lumbalis. Animals were subjected to hypoxia, hypokinesia and both combined and a control group to neither. A total of two groups of motoneurons were compared, one innervating the respiratory musculature, the other the musculature of the lower extremities, so that hypoxic hypoxia would probably affect the first group primarily and hypokinesia the second. Results indicate that neither affect the amount of RNA in the neurons of the first group but a significant increase is noted in neurons of the second group. Other significant results are reported.

Targeted Delivery of TrkB Receptor to Phrenic Motoneurons Enhances Functional Recovery of Rhythmic Phrenic Activity after Cervical Spinal Hemisection

PubMed Central

Gransee, Heather M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

2013-01-01

Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, AAV7-TrkB.FL treated rats exhibited 73±7% of pre-SH root mean squared EMG vs. only 31±11% in untreated SH rats displaying recovery (p<0.01). This study provides direct evidence that increased TrkB.FL expression in phrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that

Integration of anteroposterior and dorsoventral regulation of Phox2b transcription in cranial motoneuron progenitors by homeodomain proteins.

PubMed

Samad, Omar Abdel; Geisen, Marc J; Caronia, Giuliana; Varlet, Isabelle; Zappavigna, Vincenzo; Ericson, Johan; Goridis, Christo; Rijli, Filippo M

2004-08-01

Little is known about the molecular mechanisms that integrate anteroposterior (AP) and dorsoventral (DV) positional information in neural progenitors that specify distinct neuronal types within the vertebrate neural tube. We have previously shown that in ventral rhombomere (r)4 of Hoxb1 and Hoxb2 mutant mouse embryos, Phox2b expression is not properly maintained in the visceral motoneuron progenitor domain (pMNv), resulting in a switch to serotonergic fate. Here, we show that Phox2b is a direct target of Hoxb1 and Hoxb2. We found a highly conserved Phox2b proximal enhancer that mediates rhombomere-restricted expression and contains separate Pbx-Hox (PH) and Prep/Meis (P/M) binding sites. We further show that both the PH and P/M sites are essential for Hox-Pbx-Prep ternary complex formation and regulation of the Phox2b enhancer activity in ventral r4. Moreover, the DV factor Nkx2.2 enhances Hox-mediated transactivation via a derepression mechanism. Finally, we show that induction of ectopic Phox2b-expressing visceral motoneurons in the chick hindbrain requires the combined activities of Hox and Nkx2 homeodomain proteins. This study takes an important first step to understand how activators and repressors, induced along the AP and DV axes in response to signaling pathways, interact to regulate specific target gene promoters, leading to neuronal fate specification in the appropriate developmental context.

Dense TRPV2 immunoreactivity defines a subset of motoneurons in the dorsal lateral nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus in rat

PubMed Central

LeWinter, Robin D.; Scherrer, Grégory; Basbaum, Allan I.

2008-01-01

The transient receptor potential cation channel TRPV2 is a member of the TRPV family of proteins and is a homologue of the capsaicin/vanilloid receptor (TRPV1). Like TRPV1, TRPV2 is expressed in a subset of dorsal root ganglia (DRG) neurons that project to superficial laminae of the spinal cord dorsal horn. Because noxious heat (>52°C) activates TRPV2 in transfected cells this channel has been implicated in the processing of high intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is restricted to small diameter DRG neurons, there is significant TRPV2 immunoreactivity in a variety of CNS regions. The present report focuses on a subset of neurons in the brainstem and spinal cord of the rat including the dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the motor trigeminal nucleus. Double label immunocytochemistry with markers of motoneurons, combined with retrograde labeling, established that these cells are, in fact, motoneurons. With the exception of their smaller diameter, these cells did not differ from other motoneurons, which are only lightly TRPV2-immunoreactive. As for the majority of DLN neurons, the densely-labeled populations co-express androgen receptor and follow normal DLN ontogeny. The functional significance of the very intense TRPV2 expression in these three distinct spinal cord and brainstem motoneurons groups remains to be determined. PMID:18063314

Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

PubMed

Gemba-Nishimura, A; Inoue, T; Nakamura, S; Nakayama, K; Mochizuki, A; Shintani, S; Yoshimura, S

2010-03-31

We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and

Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

PubMed

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2014-01-01

Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

PubMed Central

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2015-01-01

Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

Effects of support unloading on inhibitory processes in motoneurons pools of postural muscles

NASA Astrophysics Data System (ADS)

Shigueva, Tatiana; Zakirova, Albina; Tomilovskaya, Elena

The purpose of the study was to investigate the effect of support unloading on characteristics of shin extensor muscles (m.soleus and m.gastrocnemius lat.) motor units` (MU) activity evoked by electrical stimulation and intensity of spinal inhibitory processes. Conditions of support unloading were reproduced by "dry" immersion (DI), that it seen to be is the most adequate ground simulation model of weightlessness [Shulzhenko E.B. et al, 1976]. The experiments were performed with participation of 10 healthy men of 20-27 years old. The subjects were divided into 2 groups. In the first one (control group) the subjects stayed in DI for 3 days without any other influences; in the second one (experimental group) in the course of DI the mechanical stimulation of soles’ support zones in the regimen of locomotion was applied daily for 20 min at the beginning of each hour for 6 hours per day [Kozlovskaya I.B., 2007]. MUs’ activity of shin muscles (mm. gastrocnemius lat. and soleus) was recorded with needle concentric electrodes during execution of the task of maintaining a small plantar flexion effort (not stronger than 7% of maximal voluntary contraction force). Single electrical pulses 0,1 ms duration were applied to n.tibialis during spontaneous MU activity. The duration of silent period (SP) following H-reflex response and presence of rebound phenomenon - an increase of MU activity at the end of SP, that is usually observed under normal conditions and reflects trace of inhibitory and excitatory processes in motoneurons pools, were analyzed [Person R.S., 1985]. Experiments were performed before, on the 2nd and 3d day of DI and on the 2nd day after its accomplishment. The Wilcoxon nonparametric criteria were used for statistical data analysis. Exposure to the conditions of support unloading was followed by significant decline of SP duration. The mean of SP duration in shin muscles before DI was 227±31,4 ms. On the 2nd and 3rd days of DI in the control group it

Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.; Ralston, Diane Daly

1988-01-01

In four rhesus monkeys wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the mesencephalic tegmentum. In three cases with injections involving the red nucleus (RN), rubrospinal fibers descended mainly contralaterally to terminate in laminae V, VI and dorsal VII of the spinal cord and in the lateral motoneuronal cell groups at the level of the cervical and lumbosacral enlargements. In all four cases the area of the interstitial nucleus of Cajal (INC) was injected, which resulted in labeled interstitiospinal fibers in the medial part of the ipsilateral ventral funiculus of the spinal cord. The results indicate that there is no major qualitative difference between the mesencephalic (RN and INC) and motor cortical projections to the spinal cord.

The expression of a motoneuron-specific serine protease, motopsin (PRSS12), after facial nerve axotomy in mice.

PubMed

Numajiri, Toshiaki; Mitsui, Shinichi; Hisa, Yasuo; Ishida, Toshihiro; Nishino, Kenichi; Yamaguchi, Nozomi

2006-01-01

Motopsin (PRSS12) is a mosaic serine protease that is preferentially expressed in motor neurons. To study the relationship between motopsin and motoneuron function, we investigated the expression of motopsin mRNA in facial nerve nuclei after facial nerve axotomy at the anterior margin of the parotid gland in mice. Neuronal function was monitored by assessing vibrissal motion in 3 months. Vibrissal behaviour on the injured side disappeared until the day 14 post-operation, and then recovered between the day 21 and 35. Motopsin expression decreased at the day 14, but markedly recovered by the day 21. In contrast, expression of growth-associated protein-43 (GAP-43) was induced at the day 3. These results suggest that the recovery of motopsin expression is correlated with the recovery of the facial motor neuronal function.

Maintenance of long-term adaptation of synaptic transmission requires axonal transport following induction in an identified crayfish motoneuron.

PubMed

Nguyen, P V; Atwood, H L

1992-03-01

Motoneurons can adapt to altered levels of electrical activity by effecting semi-permanent changes in their neuromuscular synaptic physiology. In the present study, we tested the hypothesis that maintenance of activity-dependent long-term adaptation of synaptic transmission in a crayfish abdominal extensor motoneuron (phasic axon 3) required axonal transport following induction. Intact crayfish were chronically wired for periodic in vivo stimulation of axon 3. Periodic unilateral stimulation for 3-5 consecutive days (2 h/day) induced long-term adaptation (LTA) of neuromuscular synaptic transmission in axon 3. Initial EPSP amplitudes (measured at 0.1 Hz) were significantly reduced to approximately 40% of contralateral control amplitudes over a 7-day poststimulation period. Additionally, synaptic depression during 5 Hz test stimulation of axon 3 was significantly less in chronically stimulated neurons: excitatory postsynaptic potential (EPSP) amplitudes measured after 20 min of 5 Hz test stimulation (final EPSPs) were significantly larger in conditioned neurons than in unstimulated controls. The depression of initial EPSP amplitudes persisted for 7 days postinduction, while the increased synaptic stamina persisted for 4 days but was absent at 7 days postinduction. Axotomy of axon 3 following induction of LTA had no effect on long-term maintenance of the activity-induced reduction in initial EPSP amplitudes. Initial EPSP amplitudes in conditioned, axotomized neurons were still reduced to 42% of control amplitudes over the 7-day postinduction period. In contrast, postinduction axotomy of axon 3 elicited an accelerated decay of the enhanced synaptic stamina. Following axotomy, final EPSP amplitudes were significantly larger in conditioned neurons for only 1 day poststimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

PubMed Central

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-01-01

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

PubMed

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-09-15

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

PubMed

Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

2009-08-25

The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

PubMed

Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

2004-10-01

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

Behaviorism

ERIC Educational Resources Information Center

Moore, J.

2011-01-01

Early forms of psychology assumed that mental life was the appropriate subject matter for psychology, and introspection was an appropriate method to engage that subject matter. In 1913, John B. Watson proposed an alternative: classical S-R behaviorism. According to Watson, behavior was a subject matter in its own right, to be studied by the…

Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.

PubMed

Gonzalez Porras, Maria A; Durfee, Paul; Giambini, Sebastian; Sieck, Gary C; Brinker, C Jeffrey; Mantilla, Carlos B

2018-04-01

Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods. Copyright © 2018 Elsevier Inc. All rights reserved.

The Drosophila SH2-SH3 adapter protein Dock is expressed in embryonic axons and facilitates synapse formation by the RP3 motoneuron.

PubMed

Desai, C J; Garrity, P A; Keshishian, H; Zipursky, S L; Zinn, K

1999-04-01

The Dock SH2-SH3 domain adapter protein, a homolog of the mammalian Nck oncoprotein, is required for axon guidance and target recognition by photoreceptor axons in Drosophila larvae. Here we show that Dock is widely expressed in neurons and at muscle attachment sites in the embryo, and that this expression pattern has both maternal and zygotic components. In motoneurons, Dock is concentrated in growth cones. Loss of zygotic dock function causes a selective delay in synapse formation by the RP3 motoneuron at the cleft between muscles 7 and 6. These muscles often completely lack innervation in late stage 16 dock mutant embryos. RP3 does form a synapse later in development, however, because muscles 7 and 6 are normally innervated in third-instar mutant larvae. The absence of zygotically expressed Dock also results in subtle defects in a longitudinal axon pathway in the embryonic central nervous system. Concomitant loss of both maternally and zygotically derived Dock dramatically enhances these central nervous system defects, but does not increase the delay in RP3 synaptogenesis. These results indicate that Dock facilitates synapse formation by the RP3 motoneuron and is also required for guidance of some interneuronal axons The involvement of Dock in the conversion of the RP3 growth cone into a presynaptic terminal may reflect a role for Dock-mediated signaling in remodeling of the growth cone's cytoskeleton.

Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling.

PubMed

Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1(G93A), but not ACM-hSOD1(WT), increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1(G93A)-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1(G86R) or TDP43(A315T). We further find that co-application of ACM-SOD1(G93A) with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1(G93A) induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death.

Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling

PubMed Central

Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E.; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A.; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1G93A (ACM-hSOD1G93A) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1G93A, but not ACM-hSOD1WT, increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1G93A-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1G86R or TDP43A315T. We further find that co-application of ACM-SOD1G93A with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1G93A induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death. PMID:26106294

Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes.

PubMed

Cho, Kyoung-In; Yoon, Dosuk; Qiu, Sunny; Danziger, Zachary; Grill, Warren M; Wetsel, William C; Ferreira, Paulo A

2017-05-01

The pathogenic drivers of sporadic and familial motor neuron disease (MND), such amyotrophic lateral sclerosis (ALS), are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of Ranbp2 in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and whose impairments

Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.

PubMed

Kamiyama, Daichi; McGorty, Ryan; Kamiyama, Rie; Kim, Michael D; Chiba, Akira; Huang, Bo

2015-10-12

Precise positioning of dendritic branches is a critical step in the establishment of neuronal circuitry. However, there is limited knowledge on how environmental cues translate into dendrite initiation or branching at a specific position. Here, through a combination of mutation, RNAi, and imaging experiments, we found that a Dscam-Dock-Pak1 hierarchical interaction defines the stereotypical dendrite growth site in the Drosophila aCC motoneuron. This interaction localizes the Cdc42 effector Pak1 to the plasma membrane at the dendrite initiation site before the activation of Cdc42. Ectopic expression of membrane-anchored Pak1 overrides this spatial specification of dendritogenesis, confirming its function in guiding Cdc42 signaling. We further discovered that Dscam1 localization in aCC occurs through an inter-neuronal contact that involves Dscam1 in the partner MP1 neuron. These findings elucidate a mechanism by which Dscam1 controls neuronal morphogenesis through spatial regulation of Cdc42 signaling and, subsequently, cytoskeletal remodeling. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuromodulation of reciprocal glutamatergic inhibition between antagonistic motoneurons by 5-hydroxytryptamine (5-HT) in crayfish walking system.

PubMed

Pearlstein, E; Clarac, F; Cattaert, D

1998-01-23

In an in vitro preparation of the crayfish thoracic locomotor system, paired intracellular recordings were performed from antagonistic depressor (Dep) and levator (Lev) motoneurons (MNs) that control the second joint of walking legs. Connections between these two groups of MNs consist mainly of inhibitory connections and weak electrotonic synapses. Injection of depolarizing current into a Lev MN results in a hyperpolarization in a Dep MN, and vice versa. This reciprocal glutamatergic inhibition, is not changed in the presence of the sodium channel blocker tetrodotoxin (TTX) and therefore is likely supported by a direct connection between MNs. By contrast, reciprocal inhibition is largely reduced in the presence of 5-hydroxytryptamine (5-HT; 10 microM). Direct micro-application of glutamate pressure-ejected close to an intracellularly recorded MN, evoked an inhibitory response in that MN, accompanied by a decrease of input resistance. These two effects were dramatically reduced in the presence of 5-HT. Thus 5-HT could be involved in mechanisms of dynamic reconfigurations of the neural network controlling leg movements in crayfish.

Effects of tripolar TENS on slow and fast motoneurons: a preliminary study using H-reflex recovery curve method.

PubMed

Simorgh, L; Torkaman, G; Firoozabadi, S M

2008-01-01

This study aimed at examining the effect of tripolar TENS of vertebral column on the activity of slow and fast motoneurons on 10 healthy non-athlete women aged 22.7 +/- 2.21 yrs. H-reflex recovery curve of soleus (slow) and gastrocnemius (fast) muscles were recorded before and after applying tripolar TENS. For recording of this curve, rectangular paired stimuli were applied on tibial nerve (with 40-520 ISI, frequency of 0.2 Hz and pulse width of 600 micros). Our findings showed that maximum H-reflex recovery in gastrocnemius muscle appeared in the shorter ISI, while in soleus muscle, it appeared in the longer ISI and its amplitude slightly decreased after applying tripolar TENS. It is suggested that tripolar TENS excites not only the skin but also Ia and Ib afferents in the dorsal column. A Synaptic interaction of these afferents in spinal cord causes the inhibition of type I MNs and facilitation of type II MNs. This effect can be used in muscle tone modulation.

Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

PubMed

Dideriksen, Jakob L; Holobar, Ales; Falla, Deborah

2016-08-01

Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. Copyright © 2016 the American Physiological Society.

Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James

2010-12-01

To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle

PubMed Central

Dideriksen, Jakob L.; Holobar, Ales

2016-01-01

Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. PMID:27226455

Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones

PubMed Central

Norton, Will H.; Mangoli, Maryam; Lele, Zsolt; Pogoda, Hans-Martin; Diamond, Brianne; Mercurio, Sara; Russell, Claire; Teraoka, Hiroki; Stickney, Heather L.; Rauch, Gerd-Jörg; Heisenberg, Carl-Philipp; Houart, Corinne; Schilling, Thomas F.; Frohnhoefer, Hans-Georg; Rastegar, Sepand; Neumann, Carl J.; Gardiner, R. Mark; Strähle, Uwe; Geisler, Robert; Rees, Michelle; Talbot, William S.; Wilson, Stephen W.

2009-01-01

Summary In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphé nucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins. PMID:15677724

Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.

PubMed

Norton, Will H; Mangoli, Maryam; Lele, Zsolt; Pogoda, Hans-Martin; Diamond, Brianne; Mercurio, Sara; Russell, Claire; Teraoka, Hiroki; Stickney, Heather L; Rauch, Gerd-Jörg; Heisenberg, Carl-Philipp; Houart, Corinne; Schilling, Thomas F; Frohnhoefer, Hans-Georg; Rastegar, Sepand; Neumann, Carl J; Gardiner, R Mark; Strähle, Uwe; Geisler, Robert; Rees, Michelle; Talbot, William S; Wilson, Stephen W

2005-02-01

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphenucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.

Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females.

PubMed

Garner, Sarah Rose C; Castellanos, Monica C; Baillie, Katherine E; Lian, Tianshun; Allan, Douglas W

2018-01-08

Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex-determination gene fruitless ( fru ) into the Fru MC isoform. However, in females, fru alleles that only generate Fru M isoforms failed to kill FS-Ilp7 motoneurons. This blockade of Fru M -dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer ( tra ), a gene encoding the RNA splicing activator that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the Fru M isoform is expressed. In addition, we found that Fru MC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, Fru MC -dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons. © 2018. Published by The Company of Biologists Ltd.

SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

PubMed

Romeo-Guitart, David; Leiva-Rodríguez, Tatiana; Espinosa-Alcantud, María; Sima, Núria; Vaquero, Alejandro; Domínguez-Martín, Helena; Ruano, Diego; Casas, Caty

2018-05-10

Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.

Axotomy-induced target disconnection promotes an additional death mechanism involved in motoneuron degeneration in ALS transgenic mice

PubMed Central

Haulcomb, Melissa M.; Mesnard, Nichole A.; Batka, Richard J.; Alexander, Thomas D.; Sanders, Virginia M.; Jones, Kathryn J.

2014-01-01

The target disconnection theory of amyotrophic lateral sclerosis (ALS) pathogenesis suggests disease onset is initiated by a peripheral pathological event resulting in neuromuscular junction loss and motoneuron (MN) degeneration. Pre-symptomatic mSOD1G93A mouse facial MN (FMN) are more susceptible to axotomy-induced cell death than wild-type (WT) FMN, which suggests additional CNS pathology. We have previously determined that the mSOD1 molecular response to facial nerve axotomy is phenotypically regenerative and indistinguishable from WT, whereas the surrounding microenvironment shows significant dysregulation in the mSOD1 facial nucleus. To elucidate the mechanisms underlying the enhanced mSOD1 FMN loss after axotomy, we superimposed the facial nerve axotomy model on pre-symptomatic mSOD1 mice and investigated gene expression for death receptor pathways after target disconnection by axotomy vs. disease progression. We determined that the TNFR1 death receptor pathway is involved in axotomy-induced FMN death in WT, and partially responsible for the mSOD1 FMN death. In contrast, an inherent mSOD1 CNS pathology resulted in a suppressed glial reaction and an upregulation in the Fas death pathway after target disconnection. We propose that the dysregulated mSOD1 glia fail to provide support to injured MN, leading to Fas-induced FMN death. Finally, we demonstrated that during disease progression, the mSOD1 facial nucleus displays target disconnection-induced gene expression changes that mirror those induced by axotomy. This validates the use of axotomy as an investigative tool in understanding the role of peripheral target disconnection in the pathogenesis of ALS. PMID:24424947

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels.

PubMed

Lombardo, Joseph; Harrington, Melissa A

2016-11-01

KCNQ/K v 7 channels form a slow noninactivating K + current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K v 7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K + current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K v 7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K v 7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K v 7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K v 7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K v 7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K v 7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K v 7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. Copyright © 2016 the American Physiological Society.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

PubMed Central

Lombardo, Joseph

2016-01-01

KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. PMID:27512022

Effect of restricted mobility on RNA content and nucleotide composition and on protein content in motoneurons of spinal cord anterior horns

NASA Technical Reports Server (NTRS)

Gorbunova, A. V.

1980-01-01

An investigation into the effect of hypokinesia on the ribonucleic acid (RNA) content, the nucleotide composition, and dynamics of protein content in the motoneuron of the rat spinal cord anterior horns is described. Methodology and findings are presented. The study results showed that the nucleotide composition of the total cellular RNA at all the studied periods of hypokinesia remained unchanged and is characteristic for the cytoplasmic, high polymer ribosomal RNA. This means that with a change in the functional state of the neuron the newly formed RNA of the nerve cell has the same composition of bases as the original RNA that belongs to the ribosomal type.

Multiplexing of Motor Information in the Discharge of a Collision Detecting Neuron during Escape Behaviors

PubMed Central

Fotowat, Haleh; Harrison, Reid R; Gabbiani, Fabrizio

2010-01-01

Locusts possess an identified neuron, the descending contralateral movement detector (DCMD), conveying visual information about impending collision from the brain to thoracic motor centers. We built a telemetry system to simultaneously record, in freely behaving animals, the activity of the DCMD and of motoneurons involved in jump execution. Co-contraction of antagonistic leg muscles, a required preparatory phase, was triggered after the DCMD firing rate crossed a threshold. Thereafter, the number of DCMD spikes predicted precisely motoneuron activity and jump occurrence. Additionally, the time of DCMD peak firing rate predicted that of jump. Ablation experiments suggest that the DCMD, together with a nearly identical ipsilateral descending neuron, is responsible for the timely execution of the escape. Thus, three distinct features that are multiplexed in a single neuron’s sensory response to impending collision – firing rate threshold, peak firing time, and spike count – likely control three distinct motor aspects of escape behaviors. PMID:21220105

Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

PubMed

Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

2015-01-01

Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

Evaluating Inhibition of Motoneuron Firing From Electromyogram Data to Assess Vestibular Output Using Vestibular Evoked Myogenic Potentials.

PubMed

Prakash, S R; Herrmann, Barbara S; Milojcic, Rupprecht; Rauch, Steven D; Guinan, John J

2015-01-01

Vestibular evoked myogenic potentials (VEMPs) are due to vestibular responses producing brief inhibitions of muscle contractions that are detectable in electromyographic (EMG) responses. VEMP amplitudes are traditionally measured by the peak to peak amplitude of the averaged EMG response (VEMPpp) or by a normalized VEMPpp (nVEMPpp). However, a brief EMG inhibition does not satisfy the statistical assumptions for the average to be the optimal processing strategy. Here, it is postulated that the inhibition depth of motoneuron firing is the desired metric for showing the influence of the vestibular system on the muscle system. The authors present a metric called "VEMPid" that estimates this inhibition depth from the EMG data obtained in a usual VEMP data acquisition. The goal of this article was to compare how well VEMPid, VEMPpp, and nVEMPpp track inhibition depth. To find a robust method to compare VEMPid, VEMPpp, and nVEMPpp, realistic physiological models for the inhibition of VEMP EMG signals were made using VEMP data from four measurement sessions on each of the five normal subjects. Each of the resulting 20 EMG-production models was adjusted to match the EMG autocorrelation of an individual subject and session. Simulated VEMP traces produced by these models were used to compare how well VEMPid, VEMPpp, and nVEMPpp tracked model inhibition depth. Applied to simulated and real VEMP data, VEMPid showed good test-retest consistency and greater sensitivity at low stimulus levels than VEMPpp or nVEMPpp. For large-amplitude responses, nVEMPpp and VEMPid were equivalent in their consistency across subjects and sessions, but for low-amplitude responses, VEMPid was superior. Unnormalized VEMPpp was always worse than nVEMPpp or VEMPid. VEMPid provides a more reliable measurement of vestibular function at low sound levels than the traditional nVEMPpp, without requiring a change in how VEMP tests are performed. The calculation method for VEMPid should be applicable whenever

Dense transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) immunoreactivity defines a subset of motoneurons in the dorsal lateral nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus in rat.

PubMed

Lewinter, R D; Scherrer, G; Basbaum, A I

2008-01-02

The transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) is a member of the TRPV family of proteins and is a homologue of the capsaicin/vanilloid receptor (transient receptor potential cation channel, vanilloid family, type 1, TRPV1). Like TRPV1, TRPV2 is expressed in a subset of dorsal root ganglia (DRG) neurons that project to superficial laminae of the spinal cord dorsal horn. Because noxious heat (>52 degrees C) activates TRPV2 in transfected cells this channel has been implicated in the processing of high intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is restricted to small diameter DRG neurons, there is significant TRPV2 immunoreactivity in a variety of CNS regions. The present report focuses on a subset of neurons in the brainstem and spinal cord of the rat including the dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the motor trigeminal nucleus. Double label immunocytochemistry with markers of motoneurons, combined with retrograde labeling, established that these cells are, in fact, motoneurons. With the exception of their smaller diameter, these cells did not differ from other motoneurons, which are only lightly TRPV2-immunoreactive. As for the majority of DLN neurons, the densely-labeled populations co-express androgen receptor and follow normal DLN ontogeny. The functional significance of the very intense TRPV2 expression in these three distinct spinal cord and brainstem motoneurons groups remains to be determined.

Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

PubMed

Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

2013-01-01

Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different

Emergencies in motoneuron disease.

PubMed

Finsterer, Josef; Stöllberger, Claudia

2017-08-01

Genetic and acquired motor-neuron-disorders (MNDs) may undergo acute deterioration resulting in various emergency situations. This literature review aims at summarising and discussing current knowledge about emergencies in MNDs. Emergencies that have been reported in MND patients include: respiratory, bulbar, cardiac, septic, epileptic, psychiatric, pain-related, and traumatic emergencies. Emergencies due to respiratory insufficiency have the strongest impact on morbidity and mortality in MNDs. To optimise the management of emergencies in MNDs, it is recommended to discuss these topics with the patient prior to their occurrence. After informed consent, patients may indicate their decision by signing an advance directive as to how such emergencies should be managed in case they arise. Generally, treatment of emergencies in MNDs is not at variance from treatment of similar emergencies due to other causes, but some peculiarities need to be pointed out. It is concluded that patients with MNDs may experience various emergencies during the disease course. Management of these conditions should be discussed with the patient prior to their appearance. Management of these emergencies follows general guidelines, which widely vary between countries, and depend on the availability of a patient's advance directive.

Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

PubMed Central

Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.

2011-01-01

Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCPy) alter spatiotemporal patterns of axonal growth in vivo. Static waterborne exposure to CPFO, but not CPF or TCPy, at concentrations ≥ 0.03μM from 24- to 72-h post fertilization significantly inhibited acetylcholinesterase, and high-performance liquid chromatography detected significantly more TCPy in zebrafish exposed to 0.1μM CPFO versus 1.0μM CPF. These data suggest that zebrafish lack the metabolic enzymes to activate CPF during these early developmental stages. Consistent with this, CPFO, but not CPF, significantly inhibited axonal growth of sensory neurons, primary motoneurons, and secondary motoneurons at concentrations ≥ 0.1μM. Secondary motoneurons were the most sensitive to axonal growth inhibition by CPFO, which was observed at concentrations that did not cause mortality, gross developmental defects, or aberrant somatic muscle differentiation. CPFO effects on axonal growth correlated with adverse effects on touch-induced swimming behavior, suggesting the functional relevance of these structural changes. These data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of CPF and demonstrate the relevance of zebrafish as a model for studying OP developmental neurotoxicity. PMID:21346248

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

PubMed

Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-05-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

PubMed Central

Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

2013-01-01

Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

The temporal relationship between non-respiratory burst activity of expiratory laryngeal motoneurons and phrenic apnoea during stimulation of the superior laryngeal nerve in rat

PubMed Central

Sun, Qi-Jian; Bautista, Tara G; Berkowitz, Robert G; Zhao, Wen-Jing; Pilowsky, Paul M

2011-01-01

Abstract A striking effect of stimulating the superior laryngeal nerve (SLN) is its ability to inhibit central inspiratory activity (cause ‘phrenic apnoea’), but the mechanism underlying this inhibition remains unclear. Here we demonstrate, by stimulating the SLN at varying frequencies, that the evoked non-respiratory burst activity recorded from expiratory laryngeal motoneurons (ELMs) has an intimate temporal relationship with phrenic apnoea. During 1–5 Hz SLN stimulation, occasional absences of phrenic nerve discharge (PND) occurred such that every absent PND was preceded by an ELM burst activity. During 10–20 Hz SLN stimulation, more bursts were evoked together with more absent PNDs, leading eventually to phrenic apnoea. Interestingly, subsequent microinjections of isoguvacine (10 mm, 20–40 nl) into ipsilateral Bötzinger complex (BötC) and contralateral nucleus tractus solitarii (NTS) significantly attenuated the apnoeic response but not the ELM burst activity. Our results suggest a bifurcating projection from NTS to both the caudal nucleus ambiguus and BötC, which mediates the closely related ELM burst and apnoeic response, respectively. We believe that such an intimate timing between laryngeal behaviour and breathing is crucial for the effective elaboration of the different airway protective behaviours elicited following SLN stimulation, including the laryngeal adductor reflex, swallowing and cough. PMID:21320890

DEVELOPMENT OF THE SIGMA-1 RECEPTOR IN C-TERMINALS OF MOTONEURONS AND COLOCALIZATION WITH THE N,N’-DIMETHYLTRYPTAMINE FORMING ENZYME, INDOLE-N-METHYL TRANSFERASE

PubMed Central

Mavlyutov, Timur A.; Epstein, Miles L.; Liu, Patricia; Verbny, Yakov I.; Ziskind-Conhaim, Lea; Ruoho, Arnold E.

2012-01-01

The function of the sigma-1 receptor (S1R) has been linked to modulating the activities of ion channels and G-protein coupled receptors (GPCR). In the CNS the S1R is expressed ubiquitously but is enriched in mouse motoneurons (MN), where it is localized to subsurface cisternae of cholinergic postsynaptic densities, also known as C-terminals. We found that S1R is enriched in mouse spinal MN at late stages of embryonic development when it is first visualized in the endoplasmic reticulum. S1Rs appear to concentrate at C-terminals of mouse MN only on the second week of postnatal development. We found that Indole-N-methyl transferase (INMT), an enzyme that converts tryptamine into the sigma-1 ligand dimethyltryptamine (DMT), is also localized to postsynaptic sites of C-terminals in close proximity to the S1R. This close association of INMT and SIRs suggest that DMT is synthesized locally to effectively activate S1R in MN. PMID:22265729

Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N'-dimethyltryptamine forming enzyme, indole-N-methyl transferase.

PubMed

Mavlyutov, T A; Epstein, M L; Liu, P; Verbny, Y I; Ziskind-Conhaim, L; Ruoho, A E

2012-03-29

The function of the sigma-1 receptor (S1R) has been linked to modulating the activities of ion channels and G-protein-coupled receptors (GPCR). In the CNS, the S1R is expressed ubiquitously but is enriched in mouse motoneurons (MN), where it is localized to subsurface cisternae of cholinergic postsynaptic densities, also known as C-terminals. We found that S1R is enriched in mouse spinal MN at late stages of embryonic development when it is first visualized in the endoplasmic reticulum. S1Rs appear to concentrate at C-terminals of mouse MN only on the second week of postnatal development. We found that indole-N-methyl transferase (INMT), an enzyme that converts tryptamine into the sigma-1 ligand dimethyltryptamine (DMT), is also localized to postsynaptic sites of C-terminals in close proximity to the S1R. This close association of INMT and S1Rs suggest that DMT is synthesized locally to effectively activate S1R in MN. Published by Elsevier Ltd.

ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

PubMed Central

Kaus, Anjoscha; Sareen, Dhruv

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

DTIC Science & Technology

2014-04-01

conducted experiments using intraspinal injections of AAV10-NG2Ab combined with AAV10 vector expressing neurotrophin 3 (AAV10-NT3-gfp) in adult rat...mediated delivery of NG2-Ab and neurotrophin NT3 expressing units significantly improved locomotor function following SCI. These behavioral improvements...mediated delivery of NG2-Ab combined with neurotrophin NT3 in rats that received either hemisection or contusion SCI. We found that rats that

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain

PubMed Central

RUKHADZE, I.; KAMANI, H.; KUBIN, L.

2017-01-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N > GH > GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I > GH > N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70–120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes. PMID:22205596

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

PubMed

Rukhadze, I; Kamani, H; Kubin, L

2011-12-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

Cholinergic interneurons in the feeding system of the pond snail Lymnaea stagnalis. II. N1 interneurons make cholinergic synapses with feeding motoneurons.

PubMed

Elliott, C J; Kemenes, G

1992-05-29

The N1 neurons are a population of interneurons active during the protraction phase of the feeding rhythm. All the N1 neurons are coupled by electrical synapses which persist in a high Mg/low Ca saline which blocks chemical synapses. Individual N1 spikes produce discrete electrotonic postsynaptic potentials (PSPS) in other N1 cells, but the coupling is not strong enough to ensure 1:1 firing. Bursts of N1 spikes generate compound PSPS in the feeding motoneurons. The sign (excitation or inhibition) of the N1 input corresponds with the synaptic barrage recorded during the protraction phase. Discrete PSPS are only resolved in a Hi-Di saline. Their variation in latency and number can be explained by variation in electrotonic propagation within the electrically coupled network of N1 cells. The excitatory postsynaptic potentials (ESPS) in the 1 cell are reduced by 0.5 mM antagonists hexamethonium (HMT), atropine (ATR), curare (d-TC) and by methylxylocholine (MeXCh), all of which block the excitatory cholinergic receptor (Elliott et al. (Phil. Trans. R. Soc. Lond. 336, 157-166 (Preceding paper.) (1992)). The 1 cell EPSPS were transiently blocked by phenyltrimethylammonium (PTMA), which is both an agonist and antagonist at the 1 cell excitatory acetylcholine (ACh) receptor (Elliott et al. 1992). The inhibitory postsynaptic potential (IPSP) in the 3 cell is blocked by bath applications of MeXCh and PTMA, which both abolish the response of the 3 cell to ACh (Elliott et. al. 1992). The effects of the cholinergic antagonists on the response of 4 cluster and 5 cells to N1 stimulation matches their response to ACh (Elliott et al. 1992). It is concluded that the population of N1 cells are multiaction, premotor cholinergic interneurons.

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii

PubMed Central

Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A.; Mezzarane, Rinaldo A.; Komiyama, Tomoyoshi; Ohki, Yukari

2017-01-01

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and

Connexin36 identified at morphologically mixed chemical/electrical synapses on trigeminal motoneurons and at primary afferent terminals on spinal cord neurons in adult mouse and rat

PubMed Central

Bautista, W.; McCrea, D. A.; Nagy, J. I.

2014-01-01

Morphologically mixed chemical/electrical synapses at axon terminals, with the electrical component formed by gap junctions, is common in the CNS of lower vertebrates. In mammalian CNS, evidence for morphologically mixed synapses has been obtained in only a few locations. Here, we used immunofluorescence approaches to examine the localization of the neuronally expressed gap junction forming protein connexin36 (Cx36) in relation to the axon terminal marker vesicular glutamate transporter1 (vglut1) in spinal cord and trigeminal motor nucleus (Mo5) of rat and mouse. In adult rodents, immunolabelling for Cx36 appeared exclusively as Cx36-puncta, and was widely distributed at all rostro-caudal levels in most spinal cord laminae and in the Mo5. A high proportion of Cx36-puncta was co-localized with vglut1, forming morphologically mixed synapses on motoneurons, in intermediate spinal cord lamina, and in regions of medial lamina VII, where vglut1-containing terminals associated with Cx36 converged on neurons adjacent to the central canal. Unilateral transection of lumbar dorsal roots reduced immunolabelling of both vglut1 and Cx36 in intermediate laminae and lamina IX. Further, vglut1-terminals displaying Cx36-puncta were contacted by terminals labelled for glutamic acid decarboxylase65, which is known to be contained in presynaptic terminals on large diameter primary afferents. Developmentally, mixed synapses begin to emerge in the spinal cord only after the second to third postnatal week and thereafter increase to adult levels. Our findings demonstrate that axon terminals of primary afferent origin form morphologically mixed synapses containing Cx36 in broadly distributed areas of adult rodent spinal cord and Mo5. PMID:24406437

The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

PubMed

Okamoto, Keiko; Emura, Norihito; Sato, Hajime; Fukatsu, Yuki; Saito, Mitsuru; Tanaka, Chie; Morita, Yukako; Nishimura, Kayo; Kuramoto, Eriko; Xu Yin, Dong; Furutani, Kazuharu; Okazawa, Makoto; Kurachi, Yoshihisa; Kaneko, Takeshi; Maeda, Yoshinobu; Yamashiro, Takashi; Takada, Kenji; Toyoda, Hiroki; Kang, Youngnam

2016-01-01

Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN.

Pre- and post-alpha motoneuronal control of the soleus H-reflex during sinusoidal hip movements in human spinal cord injury

PubMed Central

Knikou, Maria; Chaudhuri, Debjani; Kay, Elizabeth; Schmit, Brian D.

2006-01-01

The aim of this study was to establish the contribution of hip-mediated sensory feedback to spinal interneuronal circuits during dynamic conditions in people with incomplete spinal cord injury (SCI). Specifically, we investigated the effects of synergistic and antagonistic group I afferents on the soleus H-reflex during imposed sinusoidal hip movements. The soleus H-reflex was conditioned by stimulating the common peroneal nerve (CPN) at short (2, 3, and 4 ms) and long (80, 100, and 120 ms) conditioning test (C-T) intervals to assess the reciprocal and pre-synaptic inhibition of the soleus H-reflex, respectively. The soleus H-reflex was also conditioned by medial gastrocnemius (MG) nerve stimulation at C-T intervals ranging from 4 to 7 ms to assess changes in autogenic Ib inhibition during hip movement. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by the Biodex system while subjects were supine. The effects of sinusoidal hip movement on five leg muscles along with hip, knee, and ankle joint torques were also established during sensorimotor conditioning of the reflex. Phase-dependent modulation of antagonistic and synergistic muscle afferents was present during hip movement, with the reciprocal, pre-synaptic, and Ib inhibition to be significantly reduced during hip extension and reinforced during hip flexion. Reflexive muscle and joint torque responses – induced by the hip movement – were entrained to specific phases of hip movement. This study provides evidence that hip-mediated input acts as a controlling signal of pre- and post-alpha motoneuronal control of the soleus H-reflex. The expression of these spinal interneuronal circuits during imposed sinusoidal hip movements is discussed with respect to motor recovery in humans after SCI. PMID:16782072

The Differential Expression of Calcitonin Gene Related Peptide, alpha CGRP mRNA, Choline Acetyltransferase, and Low Affinity Nerve Growth Factor Receptor in Cranial Motoneurons After Hypoglossal Nerve Injury During Postnatal Development

DTIC Science & Technology

1996-08-21

maintenance. Since the classic neurotrophic effects ofNGF are not observed when it is bound to the low affinity receptor and since the high affmity type...is not present in motoneurons after injury this may explain why the classic NGF response is not observed (Wood et aI., 1990) and suggests that perhaps...Heumann et aI., 1987; Meyer et aI., 1992; Funakoshi et aI., 1993; Friedman et aI., 1995a). This sequencing ofneurotrophic changes may be related to the

Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica.

PubMed

Kempsell, Andrew T; Fieber, Lynne A

2014-01-01

Invertebrate models have advantages for understanding the basis of behavioral aging due to their simple nervous systems and short lifespans. The potential usefulness of Aplysia californica in aging research is apparent from its long history of neurobiological research, but it has been underexploited in this model use. Aging of simple reflexes at both single sensory neuron and neural circuit levels was studied to connect behavioral aging to neurophysiological aging. The tail withdrawal reflex (TWR), righting reflex, and biting response were measured throughout sexual maturity in 3 cohorts of hatchery-reared animals of known age. Reflex times increased and reflex amplitudes decreased significantly during aging. Aging in sensory neurons of animals with deficits in measures of the TWR and biting response resulted in significantly reduced excitability in old animals compared to their younger siblings. The threshold for firing increased while the number of action potentials in response to depolarizing current injection decreased during aging in sensory neurons, but not in tail motoneurons. Glutamate receptor-activated responses in sensory neurons also decreased with aging. In old tail motoneurons, the amplitude of evoked EPSPs following tail shock decreased, presumably due to reduced sensory neuron excitability during aging. The results were used to develop stages of aging relevant to both hatchery-reared and wild-caught Aplysia. Aplysia is a viable aging model in which the contributions of differential aging of components of neural circuits may be assessed.

Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica

PubMed Central

Kempsell, Andrew T.; Fieber, Lynne A.

2014-01-01

Invertebrate models have advantages for understanding the basis of behavioral aging due to their simple nervous systems and short lifespans. The potential usefulness of Aplysia californica in aging research is apparent from its long history of neurobiological research, but it has been underexploited in this model use. Aging of simple reflexes at both single sensory neuron and neural circuit levels was studied to connect behavioral aging to neurophysiological aging. The tail withdrawal reflex (TWR), righting reflex, and biting response were measured throughout sexual maturity in 3 cohorts of hatchery-reared animals of known age. Reflex times increased and reflex amplitudes decreased significantly during aging. Aging in sensory neurons of animals with deficits in measures of the TWR and biting response resulted in significantly reduced excitability in old animals compared to their younger siblings. The threshold for firing increased while the number of action potentials in response to depolarizing current injection decreased during aging in sensory neurons, but not in tail motoneurons. Glutamate receptor-activated responses in sensory neurons also decreased with aging. In old tail motoneurons, the amplitude of evoked EPSPs following tail shock decreased, presumably due to reduced sensory neuron excitability during aging. The results were used to develop stages of aging relevant to both hatchery-reared and wild-caught Aplysia. Aplysia is a viable aging model in which the contributions of differential aging of components of neural circuits may be assessed. PMID:24847260

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

PubMed

Hariharan, Praveen; Balzer, Jeffery R; Anetakis, Katherine; Crammond, Donald J; Thirumala, Parthasarathy D

2018-01-01

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

The compensatory interaction between motor unit firing behavior and muscle force during fatigue

PubMed Central

De Luca, Carlo J.; Kline, Joshua C.

2016-01-01

Throughout the literature, different observations of motor unit firing behavior during muscle fatigue have been reported and explained with varieties of conjectures. The disagreement amongst previous studies has resulted, in part, from the limited number of available motor units and from the misleading practice of grouping motor unit data across different subjects, contractions, and force levels. To establish a more clear understanding of motor unit control during fatigue, we investigated the firing behavior of motor units from the vastus lateralis muscle of individual subjects during a fatigue protocol of repeated voluntary constant force isometric contractions. Surface electromyographic decomposition technology provided the firings of 1,890 motor unit firing trains. These data revealed that to sustain the contraction force as the muscle fatigued, the following occurred: 1) motor unit firing rates increased; 2) new motor units were recruited; and 3) motor unit recruitment thresholds decreased. Although the degree of these adaptations was subject specific, the behavior was consistent in all subjects. When we compared our empirical observations with those obtained from simulation, we found that the fatigue-induced changes in motor unit firing behavior can be explained by increasing excitation to the motoneuron pool that compensates for the fatigue-induced decrease in muscle force twitch reported in empirical studies. Yet, the fundamental motor unit control scheme remains invariant throughout the development of fatigue. These findings indicate that the central nervous system regulates motor unit firing behavior by adjusting the operating point of the excitation to the motoneuron pool to sustain the contraction force as the muscle fatigues. PMID:27385798

The compensatory interaction between motor unit firing behavior and muscle force during fatigue.

PubMed

Contessa, Paola; De Luca, Carlo J; Kline, Joshua C

2016-10-01

Throughout the literature, different observations of motor unit firing behavior during muscle fatigue have been reported and explained with varieties of conjectures. The disagreement amongst previous studies has resulted, in part, from the limited number of available motor units and from the misleading practice of grouping motor unit data across different subjects, contractions, and force levels. To establish a more clear understanding of motor unit control during fatigue, we investigated the firing behavior of motor units from the vastus lateralis muscle of individual subjects during a fatigue protocol of repeated voluntary constant force isometric contractions. Surface electromyographic decomposition technology provided the firings of 1,890 motor unit firing trains. These data revealed that to sustain the contraction force as the muscle fatigued, the following occurred: 1) motor unit firing rates increased; 2) new motor units were recruited; and 3) motor unit recruitment thresholds decreased. Although the degree of these adaptations was subject specific, the behavior was consistent in all subjects. When we compared our empirical observations with those obtained from simulation, we found that the fatigue-induced changes in motor unit firing behavior can be explained by increasing excitation to the motoneuron pool that compensates for the fatigue-induced decrease in muscle force twitch reported in empirical studies. Yet, the fundamental motor unit control scheme remains invariant throughout the development of fatigue. These findings indicate that the central nervous system regulates motor unit firing behavior by adjusting the operating point of the excitation to the motoneuron pool to sustain the contraction force as the muscle fatigues. Copyright © 2016 the American Physiological Society.

Sex differences in neuromuscular androgen receptor expression and sociosexual behavior in a sex changing fish

PubMed Central

Pradhan, Devaleena S.; Thonkulpitak, Kevin; Drilling, Cathleen; Black, Michael; Grober, Matthew S.

2017-01-01

Androgen signaling, via receptor binding, is critical for regulating the physiological and morphological foundations of male-typical reproductive behavior in vertebrates. Muscles essential for male courtship behavior and copulation are highly sensitive to androgens. Differences in the distribution and density of the androgen receptor (AR) are important for maintaining dimorphic musculature and thus may provide for anatomical identification of sexually selected traits. In Lythrypnus dalli, a bi-directional hermaphroditic teleost fish, both sexes produce agonistic approach displays, but reproductive behavior is sexually dimorphic. The male-specific courtship behavior is characterized by rapid jerky movements (involving dorsal fin erection) towards a female or around their nest. Activation of the supracarinalis muscle is involved in dorsal fin contributions to both agonistic and sociosexual behavior in other fishes, suggesting that differences in goby sexual behavior may be reflected in sexual dimorphism in AR signaling in this muscle. We examined sex differences in the local distribution of AR in supracarinalis muscle and spinal cord. Our results demonstrate that males do express more AR in the supracarinalis muscle relative to females, but there was no sex difference in the number of spinal motoneurons expressing AR. Interestingly, AR expression in the supracarinalis muscle was also related to rates of sociosexual behavior in males, providing evidence that sexual selection may influence muscle androgenic sensitivity to enhance display vigor. Sex differences in the distribution and number of cells expressing AR in the supracarinalis muscle may underlie the expression of dimorphic behaviors in L. dalli. PMID:28520775

Phrenic Motor Unit Recruitment during Ventilatory and Non-Ventilatory Behaviors

PubMed Central

Mantilla, Carlos B.; Sieck, Gary C.

2011-01-01

Phrenic motoneurons are located in the cervical spinal cord and innervate the diaphragm muscle, the main inspiratory muscle in mammals. Similar to other skeletal muscles, phrenic motoneurons and diaphragm muscle fibers form motor units which are the final element of neuromotor control. In addition to their role in sustaining ventilation, phrenic motor units are active in other non-ventilatory behaviors important for airway clearance such as coughing or sneezing. Diaphragm muscle fibers comprise all fiber types and are commonly classified based on expression of contractile proteins including myosin heavy chain isoforms. Although there are differences in contractile and fatigue properties across motor units, there is a matching of properties for the motor neuron and muscle fibers within a motor unit. Motor units are generally recruited in order such that fatigue-resistant motor units are recruited earlier and more often than more fatigable motor units. Thus, in sustaining ventilation, fatigue-resistant motor units are likely required. Based on a series of studies in cats, hamsters and rats, an orderly model of motor unit recruitment was proposed that takes into consideration the maximum forces generated by single type-identified diaphragm muscle fibers as well as the proportion of the different motor unit types. Using this model, eupnea can be accomplished by activation of only slow-twitch diaphragm motor units and only a subset of fast-twitch, fatigue-resistant units. Activation of fast-twitch fatigable motor units only becomes necessary when accomplishing tasks that require greater force generation by the diaphragm muscle, e.g., sneezing and coughing. PMID:21763470

Phrenic motor unit recruitment during ventilatory and non-ventilatory behaviors.

PubMed

Mantilla, Carlos B; Sieck, Gary C

2011-10-15

Phrenic motoneurons are located in the cervical spinal cord and innervate the diaphragm muscle, the main inspiratory muscle in mammals. Similar to other skeletal muscles, phrenic motoneurons and diaphragm muscle fibers form motor units which are the final element of neuromotor control. In addition to their role in sustaining ventilation, phrenic motor units are active in other non-ventilatory behaviors important for airway clearance such as coughing or sneezing. Diaphragm muscle fibers comprise all fiber types and are commonly classified based on expression of contractile proteins including myosin heavy chain isoforms. Although there are differences in contractile and fatigue properties across motor units, there is a matching of properties for the motor neuron and muscle fibers within a motor unit. Motor units are generally recruited in order such that fatigue-resistant motor units are recruited earlier and more often than more fatigable motor units. Thus, in sustaining ventilation, fatigue-resistant motor units are likely required. Based on a series of studies in cats, hamsters and rats, an orderly model of motor unit recruitment was proposed that takes into consideration the maximum forces generated by single type-identified diaphragm muscle fibers as well as the proportion of the different motor unit types. Using this model, eupnea can be accomplished by activation of only slow-twitch diaphragm motor units and only a subset of fast-twitch, fatigue-resistant units. Activation of fast-twitch fatigable motor units only becomes necessary when accomplishing tasks that require greater force generation by the diaphragm muscle, e.g., sneezing and coughing. Copyright © 2011 Elsevier B.V. All rights reserved.

Somatotopy in the Medullary Dorsal Horn As a Basis for Orofacial Reflex Behavior

PubMed Central

Panneton, W. Michael; Pan, BingBing; Gan, Qi

2017-01-01

The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I–V. Projections to lamina II exhibited the most focused somatotopy when individual cases were compared. Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus resulted in labeled neurons almost solely in lamina V of the trigeminocervical complex. The distribution of these labeled neurons paralleled the somatotopy of primary afferent fibers, e.g., those labeled after FG injections into a functional group of motoneurons innervating lip musculature were found most rostrally while those labeled after injections into motoneurons innervating snout, periocular and preauricular muscles, respectively, were found at progressively more caudal levels. Anterograde transport of injections of biotinylated dextran amine into lamina V at different rostrocaudal levels of the trigeminocervical complex confirmed the notion that the somatotopy of orofacial sensory fields parallels the musculotopy of facial motor neurons. These data suggest that neurons in lamina V are important interneurons in a simple orofacial reflex circuit consisting of a sensory neuron, interneuron and motor neuron. Moreover, the somatotopy of primary afferent fibers from the head and neck confirms the “onion skin hypothesis” and suggests rostral cervical dermatomes blend seamlessly with “cranial dermatomes.” The

Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When Compared with Other Brainstem Motor Systems

PubMed Central

Hernández, Rosendo G.; Silva-Hucha, Silvia; Morcuende, Sara; de la Cruz, Rosa R.; Pastor, Angel M.; Benítez-Temiño, Beatriz

2017-01-01

Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons. In brainstem samples, brain-derived neurotrophic factor was present both in extraocular and facial motoneuron somata, and to a lesser degree, in hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei, while facial and hypoglossal motoneurons were almost devoid of this protein. Finally, nerve growth factor was not present in the soma of any group of motoneurons, although it was present in dendrites of motoneurons located in the neuropil. Neuropil optical density levels were higher in extraocular motoneuron nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be originated in target muscles, since Western blot analyses revealed the presence of the three molecules in all sampled muscles, to a larger extent in extraocular muscles when compared with facial and tongue muscles. We suggest that the different neurotrophin availability could be related to the particular resistance of extraocular motoneurons to neurodegeneration. PMID:28744196

Interneuronal Mechanism for Tinbergen’s Hierarchical Model of Behavioral Choice

PubMed Central

Pirger, Zsolt; Crossley, Michael; László, Zita; Naskar, Souvik; Kemenes, György; O’Shea, Michael; Benjamin, Paul R.; Kemenes, Ildikó

2014-01-01

Summary Recent studies of behavioral choice support the notion that the decision to carry out one behavior rather than another depends on the reconfiguration of shared interneuronal networks [1]. We investigated another decision-making strategy, derived from the classical ethological literature [2, 3], which proposes that behavioral choice depends on competition between autonomous networks. According to this model, behavioral choice depends on inhibitory interactions between incompatible hierarchically organized behaviors. We provide evidence for this by investigating the interneuronal mechanisms mediating behavioral choice between two autonomous circuits that underlie whole-body withdrawal [4, 5] and feeding [6] in the pond snail Lymnaea. Whole-body withdrawal is a defensive reflex that is initiated by tactile contact with predators. As predicted by the hierarchical model, tactile stimuli that evoke whole-body withdrawal responses also inhibit ongoing feeding in the presence of feeding stimuli. By recording neurons from the feeding and withdrawal networks, we found no direct synaptic connections between the interneuronal and motoneuronal elements that generate the two behaviors. Instead, we discovered that behavioral choice depends on the interaction between two unique types of interneurons with asymmetrical synaptic connectivity that allows withdrawal to override feeding. One type of interneuron, the Pleuro-Buccal (PlB), is an extrinsic modulatory neuron of the feeding network that completely inhibits feeding when excited by touch-induced monosynaptic input from the second type of interneuron, Pedal-Dorsal12 (PeD12). PeD12 plays a critical role in behavioral choice by providing a synaptic pathway joining the two behavioral networks that underlies the competitive dominance of whole-body withdrawal over feeding. PMID:25155505

Behavioral Humanism.

ERIC Educational Resources Information Center

Thoresen, Carl E.

Behavioral humanism is defined as the synthesis of behavioral techniques with humanistic goals. Contemporary humanism, especially humanistic psychology, offers directions for the kind of behavior that individuals should be able to engage in; contemporary behaviorism offers principles and procedures to help individuals increase their humanistic…

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity

NASA Astrophysics Data System (ADS)

Horn, E.; Agricola, H.; Böser, S.; Förster, S.; Kämper, G.; Riewe, P.; Sebastian, C.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (μg). The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of μg- or 3g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Motoneuron firing in amyotrophic lateral sclerosis (ALS)

PubMed Central

de Carvalho, Mamede; Eisen, Andrew; Krieger, Charles; Swash, Michael

2014-01-01

Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials. PMID:25294995

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

PubMed

DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship

Behavioral Economics

PubMed Central

Niileksela, Christopher R.; Kaplan, Brent A.

2013-01-01

In recent years, behavioral economics has gained much attention in psychology and public policy. Despite increased interest and continued basic experimental studies, the application of behavioral economics to therapeutic settings remains relatively sparse. Using examples from both basic and applied studies, we provide an overview of the principles comprising behavioral economic perspectives and discuss implications for behavior analysts in practice. A call for further translational research is provided. PMID:25729506

Behavioral Medicine.

ERIC Educational Resources Information Center

Garfield, Sol L., Ed.

1982-01-01

Contains 18 articles discussing the uses of behavioral medicine in such areas as obesity, smoking, hypertension, and headache. Reviews include discussions of behavioral medicine and insomnia, chronic pain, asthma, peripheral vascular disease, and coronary-prone behavior. Newly emerging topics include gastrointestinal disorders, arthritis,…

Tris (2-butoxyethyl) phosphate affects motor behavior and axonal growth in zebrafish (Danio rerio) larvae.

PubMed

Jiang, Fan; Liu, Jue; Zeng, Xinyue; Yu, Liqin; Liu, Chunsheng; Wang, Jianghua

2018-05-01

Tris (2-butoxyethyl) phosphate (TBOEP) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. Recently, the reproductive and developmental toxicology of TBOEP has been reported. However, fewer studies have assessed the neurotoxic effects in zebrafish (Danio rerio) larvae. In this study, zebrafish embryos were subjected to waterborne exposure of TBOEP at 0, 50, 500, 1500 and 2500 μg/L from 2 to 144-h post-fertilization (hpf). Behavioral measurements showed that TBOEP exposure reduced embryonic spontaneous movement and decreased swimming speed of larvae in response to dark stimulation. In accordance with these motor effects, TBOEP treatment reduced neuron-specific GFP expression in transgenic Tg (HuC-GFP) zebrafish larvae and inhibited the growth of secondary motoneurons, as well as decreased expression of marker genes related to central nervous system development in TBOEP treated group. Furthermore, increased concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduction of SOD activity were detected in TBOEP exposure group. The present results showed that the alteration in motor neuron and oxidative stress could together lead to the motor behavior alterations induced by TBOEP. Copyright © 2018 Elsevier B.V. All rights reserved.

Excitotoxic lesions of the nucleus paragigantocellularis facilitate male sexual behavior but attenuate female sexual behavior in rats.

PubMed

Normandin, J J; Murphy, A Z

2011-02-23

Little is known regarding the descending inhibitory control of genital reflexes such as ejaculation and vaginal contractions. The brainstem nucleus paragigantocellularis (nPGi) projects bilaterally to the lumbosacral motoneuron pools that innervate the genital musculature of both male and female rats. Electrolytic nPGi lesions facilitate ejaculation in males, leading to the hypothesis that the nPGi is the source of descending inhibition to genital reflexes. However, the function of the nPGi in female sexual behavior remains to be elucidated. To this end, male and female rats received bilateral excitotoxic fiber-sparing lesions of the nPGi, and sexual behavior and sexual behavior-induced Fos expression were examined. In males, nPGi lesions facilitated copulation, supporting the hypothesis that the nPGi, and not fibers-of-passage, is the source of descending inhibition of genital reflexes in male rats. nPGi lesions in males did not alter sexual behavior-induced Fos expression in any brain region examined. nPGi-lesioned females spent significantly less time mating with stimulus males and had significantly longer ejaculation-return latencies compared to baseline. These results did not significantly differ from control females, but this trend warranted further analysis of the reinforcing value of sexual behavior. Both lesioned and non-lesioned females formed a conditioned place preference (CPP) for artificial vaginocervical stimulation (aVCS). However, post-reinforcement, nPGi-lesioned females did not differ in the percentage of time spent in the non-reinforced chamber versus the reinforced chamber, suggesting a weakened CPP for aVCS. nPGi lesions in females reduced sexual behavior-induced Fos expression throughout the hypothalamus and amygdala. Taken together, these results suggest that while nPGi lesions in males facilitate copulation, such lesions in females attenuate several aspects of sexual behavior resulting in a reduction in the rewarding value of copulation

Behavior Matters

PubMed Central

Fisher, Edwin B.; Fitzgibbon, Marian L.; Glasgow, Russell E.; Haire-Joshu, Debra; Hayman, Laura L.; Kaplan, Robert M.; Nanney, Marilyn S.; Ockene, Judith K.

2011-01-01

Behavior has a broad and central role in health. Behavioral interventions can be effectively used to prevent disease, improve management of existing disease, increase quality of life, and reduce healthcare costs. A summary is presented of evidence for these conclusions in cardiovascular disease/diabetes, cancer, and HIV/AIDS as well as with key risk factors: tobacco use, poor diet, physical inactivity, and excessive alcohol consumption. For each, documentation is made of (1) moderation of genetic and other fundamental biological influences by behaviors and social–environmental factors, (2) impacts of behaviors on health, (3) success of behavioral interventions in prevention, (4) disease management, (5) and quality of life, and (6) improvements in the health of populations through behavioral health promotion programs. Evidence indicates the cost effectiveness and value of behavioral interventions, especially relative to other common health services, as well as the value they add in terms of quality of life. Pertinent to clinicians and their patients as well as to health policy and population health, the benefits of behavioral interventions extend beyond impacts on a particular disease or risk factor. Rather, they include broad effects and benefits on prevention, disease management, and well-being across the life span. Among priorities for dissemination research, the application of behavioral approaches is challenged by diverse barriers, including socioeconomic barriers linked to health disparities. However, behavioral approaches including those emphasizing community and social influences appear to be useful in addressing such challenges. In sum, behavioral approaches should have a central place in prevention and health care of the 21st century. PMID:21496745

Behavioral economics

PubMed Central

Hursh, Steven R.

1984-01-01

Economics, like behavioral psychology, is a science of behavior, albeit highly organized human behavior. The value of economic concepts for behavioral psychology rests on (1) their empirical validity when tested in the laboratory with individual subjects and (2) their uniqueness when compared to established behavioral concepts. Several fundamental concepts are introduced and illustrated by reference to experimental data: open and closed economies, elastic and inelastic demand, and substitution versus complementarity. Changes in absolute response rate are analyzed in relation to elasticity and intensity of demand. The economic concepts of substitution and complementarity are related to traditional behavioral studies of choice and to the matching relation. The economic approach has many implications for the future of behavioral research and theory. In general, economic concepts are grounded on a dynamic view of reinforcement. The closed-economy methodology extends the generality of behavioral principles to situations in which response rate and obtained rate of reinforcement are interdependent. Analysis of results in terms of elasticity and intensity of demand promises to provide a more direct method for characterizing the effects of “motivational” variables. Future studies of choice should arrange heterogeneous reinforcers with varying elasticities, use closed economies, and modulate scarcity or income. The economic analysis can be extended to the study of performances that involve subtle discriminations or skilled movements that vary in accuracy or quality as opposed to rate or quantity, and thus permit examination of time/accuracy trade-offs. PMID:16812401

Behavioral epigenetics

PubMed Central

Lester, Barry M.; Tronick, Edward; Nestler, Eric; Abel, Ted; Kosofsky, Barry; Kuzawa, Christopher W.; Marsit, Carmen J.; Maze, Ian; Meaney, Michael J.; Monteggia, Lisa M.; Reul, Johannes M. H. M.; Skuse, David H.; Sweatt, J. David; Wood, Marcelo A.

2013-01-01

Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology. This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level. PMID:21615751

Biological impacts of glyphosate on morphology, embryo biomechanics and larval behavior in zebrafish (Danio rerio).

PubMed

Zhang, Shuhui; Xu, Jia; Kuang, Xiangyu; Li, Shibao; Li, Xiang; Chen, Dongyan; Zhao, Xin; Feng, Xizeng

2017-08-01

All of these days, residues of herbicides such as glyphosate are widely distributed in the environment. The ubiquitous use of glyphosate has drawn extensive attention to its toxicity as an organic pollutant. In this study, we employed larval zebrafish as an animal model to evaluate the effect of different concentrations of glyphosate on early development via morphological, biomechanics, behavioral and physiological analyses. Morphological results showed that an obvious delay occurred in the epiboly process and body length, eye and head area were reduced at concentrations higher than 10 mg/L. The expression of ntl (no tail) shortened and krox20 (also known as Egr2b, early growth response 2b) changed as the glyphosate concentration increased, but there was no change in the expression of shh (sonic hedgehog). In addition, biomechanical analysis of the elasticity of chorion indicated that treated embryos' surface tension was declined. Furthermore, a 48-h locomotion test revealed that embryonic exposure to glyphosate significantly elevated locomotor activities, which is probably attributed to motoneuronal damage. The decreased surface tension of chorion and the increased locomotive activities may contribute to the hatching rates after glyphosate treatment. Our study enriches the researches of evaluating glyphosate toxicity and probablely plays a warning role in herbicides used in farming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder.

PubMed

Valencia Garcia, Sara; Brischoux, Frédéric; Clément, Olivier; Libourel, Paul-Antoine; Arthaud, Sébastien; Lazarus, Michael; Luppi, Pierre-Hervé; Fort, Patrice

2018-02-05

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.

Energy behavior

SciTech Connect

Stern, P.C.; Kirkpatrick, E.M.

1977-12-01

The energy crisis is approached as a social and psychological problem with solutions based on an understanding of principles of attitude and behavior change. Propaganda calling for voluntary energy conservation has had little effect, and incentive systems present several serious drawbacks. The author believes that the ideal role of both incentives and persuasion is to influence the behavior of groups who in turn would maintain individual behavior and attitudes by social pressure. Thus a program of incentives and education directed at groups of people may effectively increase conservation and change related attitudes without increasing reactance. The author presents 2 strategiesmore » to cope with the energy problem: one relies strongly on government action, combining appeal to national feelings and a threat to future coercion to change attitudes and behavior; the other uses incentives to communities for conservation and development of renewable energy resources.« less

Behavior change

USDA-ARS?s Scientific Manuscript database

This brief entry presents the mediating-moderating variable model as a conceptual framework for understanding behavior change in regard to physical activity/exercise and adiposity. The ideas are applied to real world situations....

Behavioral addictions.

PubMed

Robbins, T W; Clark, L

2015-02-01

Behavioral addictions are slowly becoming recognized as a valid category of psychiatric disorder as shown by the recent allocation of pathological gambling to this category in DSM-5. However, several other types of psychiatric disorder proposed to be examples of behavioral addictions have yet to be accorded this formal acknowledgment and are dispersed across other sections of the DSM-5. This brief review marks this important point in the evolution of this concept and looks to future investigation of behavioral addictions with the theoretical frameworks currently being used successfully to investigate substance addiction and obsessive-compulsive disorder, in a potentially new spectrum of impulsive-compulsive disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lateral rectus myositis mimicking an abducens nerve palsy in a pregnant woman.

PubMed

Haslinda, Abd-Rahim; Shatriah, Ismail; Azhany, Yaakub; Nik-Ahmad-Zuky, Nik-Lah; Yunus, Rohaizan

2014-01-01

Myositis is a rare unknown inflammatory disorder of the skeletal muscle tissue. Generalized inflammatory myopathies, polymyositis, and dermatomyositis have been reported during pregnancy. Isolated orbital myositis in pregnancy has not been previously described in the literature. The authors report a case of left isolated orbital myositis in a primigravida at 38 weeks gestation affecting the patient's left lateral rectus muscle. MRI of the orbit was consistent with the diagnosis. She showed remarkable clinical improvement with oral corticosteroids therapy.

Brain circuits for mating behavior in cats and brain activations and de-activations during sexual stimulation and ejaculation and orgasm in humans.

PubMed

Holstege, Gert; Huynh, Hieu K

2011-05-01

In cats, there exists a descending system that controls the posture necessary for mating behavior. A key role is played by the mesencephalic periaqueductal gray (PAG), which maintains strong specific projections to the nucleus retroambiguus located laterally in the most caudal medulla. The NRA, in turn, has direct access to motoneurons in the lumbosacral cord that produce the mating posture. This pathway is slightly different in males and females, but in females its strength fluctuates strongly depending on whether or not the cat is in heat. This way the PAG determines whether or not mating can take place. Via the PAG many other regions in the limbic system as well as in the prefrontal cortex and insula can influence mating behavior. In humans, the brain also controls responses to sexual stimulation as well as ejaculation in men and orgasm in women. Neuroimaging techniques show activations and de-activations but are not able to verify whether the PAG has a similar effect as in cats. PET-scanning results revealed that there is activation in the upper brainstem and cerebellum, as well as insula in men and in the somatomotor and somatosensory cortex in women. During sexual stimulation, but especially during ejaculation and orgasm there was strong de-activation mainly on the left side in the temporal lobe and ventral prefrontal cortex. These neuroimaging results show the importance of lowering the level of alertness regarding your immediate environment (left hemisphere) to have proper sexual behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Aggressive Behavior

MedlinePlus

... be outlined. Not all methods work on all children, so there will be a certain amount of trial and reassessment. Once several effective ways are found to reward good behavior and discourage bad, they can be used in establishing an approach ...

Behavior Modification

ERIC Educational Resources Information Center

Boardman, Randolph M.

2010-01-01

In a perfect world, students would never talk back to school staff and never argue or fight with each other. They would complete all their assigned tasks, and disciplinary actions never would be needed. Unfortunately, people don't live in a perfect world. Student behavior is a daily concern. Teachers continue to refer students to the office as a…

Challenging Behavior.

ERIC Educational Resources Information Center

Reichle, Joe, Ed.; DePaepe, Paris, Ed.

1991-01-01

The articles in this feature or theme issue describe successful approaches to positive, community-based management of severe challenging behavior. Programs include: a train-the-trainer strategy for inservice training used across the country; the use of student volunteers as community integration facilitators; a school-based intervention project…

Model Behavior

ERIC Educational Resources Information Center

Holloway, John

2006-01-01

There are dozens of books and hundreds of resources that address the issue of character development in students: how to raise them to be good people, how to teach them to be good citizens, how to help them to make good decisions. Little is written, however, about the character development of principals and school leaders, whose behavior is a model…

Stimulation of pontine reticular formation in monkeys with strabismus.

PubMed

Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2013-10-29

Saccade disconjugacy in strabismus could result from any of a number of factors, including abnormalities of eye muscles, the plant, motoneurons, near response cells, or atypical tuning of neurons in saccade-related areas of the brain. This study was designed to investigate the possibility that saccade disconjugacy in strabismus is associated with abnormalities in paramedian pontine reticular formation (PPRF). We applied microstimulation to 22 sites in PPRF and 20 sites in abducens nucleus in three rhesus macaque monkeys (one normal, one esotrope, and one exotrope). When mean velocity was compared between the two eyes, a slight difference was found for 1/5 sites in the normal animal. Significant differences were found for 5/6 sites in an esotrope and 10/11 sites in an exotrope. For five sites in the strabismic monkeys, the directions of evoked movements differed by more than 40° between the two eyes. When stimulation was applied to abducens nucleus (20 sites), the ipsilateral eye moved faster for 4/6 sites in the normal animal and all nine sites in the esotrope. For the exotrope, however, the left eye always moved faster, even for three sites on the right side. For the strabismic animals, stimulation of abducens nucleus often caused a different eye to move faster than stimulation of PPRF. These data suggest that PPRF is organized at least partly monocularly in strabismus and that disconjugate saccades are at least partly a consequence of unbalanced saccadic commands being sent to the two eyes.

OPEC behavior

NASA Astrophysics Data System (ADS)

Yang, Bo

This thesis aims to contribute to a further understanding of the real dynamics of OPEC production behavior and its impacts on the world oil market. A literature review in this area shows that the existing studies on OPEC still have some major deficiencies in theoretical interpretation and empirical estimation technique. After a brief background review in chapter 1, chapter 2 tests Griffin's market-sharing cartel model on the post-Griffin time horizon with a simultaneous system of equations, and an innovative hypothesis of OPEC's behavior (Saudi Arabia in particular) is then proposed based on the estimation results. Chapter 3 first provides a conceptual analysis of OPEC behavior under the framework of non-cooperative collusion with imperfect information. An empirical model is then constructed and estimated. The results of the empirical studies in this thesis strongly support the hypothesis that OPEC has operated as a market-sharing cartel since the early 1980s. In addition, the results also provide some support of the theory of non-cooperative collusion under imperfect information. OPEC members collude under normal circumstances and behave competitively at times in response to imperfect market signals of cartel compliance and some internal attributes. Periodic joint competition conduct plays an important role in sustaining the collusion in the long run. Saudi Arabia acts as the leader of the cartel, accommodating intermediate unfavorable market development and punishing others with a tit-for-tat strategy in extreme circumstances.

Behavioral epigenetics.

PubMed

Moore, David S

2017-01-01

Why do we grow up to have the traits we do? Most 20th century scientists answered this question by referring only to our genes and our environments. But recent discoveries in the emerging field of behavioral epigenetics have revealed factors at the interface between genes and environments that also play crucial roles in development. These factors affect how genes work; scientists now know that what matters as much as which genes you have (and what environments you encounter) is how your genes are affected by their contexts. The discovery that what our genes do depends in part on our experiences has shed light on how Nature and Nurture interact at the molecular level inside of our bodies. Data emerging from the world's behavioral epigenetics laboratories support the idea that a person's genes alone cannot determine if, for example, he or she will end up shy, suffering from cardiovascular disease, or extremely smart. Among the environmental factors that can influence genetic activity are parenting styles, diets, and social statuses. In addition to influencing how doctors treat diseases, discoveries about behavioral epigenetics are likely to alter how biologists think about evolution, because some epigenetic effects of experience appear to be transmissible from generation to generation. This domain of research will likely change how we think about the origins of human nature. WIREs Syst Biol Med 2017, 9:e1333. doi: 10.1002/wsbm.1333 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

A Central Mesencephalic Reticular Formation Projection to the Supraoculomotor Area in Macaque Monkeys

PubMed Central

Bohlen, Martin O.; Warren, Susan; May, Paul J.

2015-01-01

The central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system’s premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic reticular formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic reticular formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic reticular formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad. PMID:25859632

A central mesencephalic reticular formation projection to the supraoculomotor area in macaque monkeys.

PubMed

Bohlen, Martin O; Warren, Susan; May, Paul J

2016-05-01

The central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system's premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic reticular formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic reticular formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic reticular formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad.

Variations in Static Force Control and Motor Unit Behavior with Error Amplification Feedback in the Elderly.

PubMed

Chen, Yi-Ching; Lin, Linda L; Lin, Yen-Ting; Hu, Chia-Ling; Hwang, Ing-Shiou

2017-01-01

Error amplification (EA) feedback is a promising approach to advance visuomotor skill. As error detection and visuomotor processing at short time scales decline with age, this study examined whether older adults could benefit from EA feedback that included higher-frequency information to guide a force-tracking task. Fourteen young and 14 older adults performed low-level static isometric force-tracking with visual guidance of typical visual feedback and EA feedback containing augmented high-frequency errors. Stabilogram diffusion analysis was used to characterize force fluctuation dynamics. Also, the discharge behaviors of motor units and pooled motor unit coherence were assessed following the decomposition of multi-channel surface electromyography (EMG). EA produced different behavioral and neurophysiological impacts on young and older adults. Older adults exhibited inferior task accuracy with EA feedback than with typical visual feedback, but not young adults. Although stabilogram diffusion analysis revealed that EA led to a significant decrease in critical time points for both groups, EA potentiated the critical point of force fluctuations [Formula: see text], short-term effective diffusion coefficients (Ds), and short-term exponent scaling only for the older adults. Moreover, in older adults, EA added to the size of discharge variability of motor units and discharge regularity of cumulative discharge rate, but suppressed the pooled motor unit coherence in the 13-35 Hz band. Virtual EA alters the strategic balance between open-loop and closed-loop controls for force-tracking. Contrary to expectations, the prevailing use of closed-loop control with EA that contained high-frequency error information enhanced the motor unit discharge variability and undermined the force steadiness in the older group, concerning declines in physiological complexity in the neurobehavioral system and the common drive to the motoneuronal pool against force destabilization.

Variations in Static Force Control and Motor Unit Behavior with Error Amplification Feedback in the Elderly

PubMed Central

Chen, Yi-Ching; Lin, Linda L.; Lin, Yen-Ting; Hu, Chia-Ling; Hwang, Ing-Shiou

2017-01-01

Error amplification (EA) feedback is a promising approach to advance visuomotor skill. As error detection and visuomotor processing at short time scales decline with age, this study examined whether older adults could benefit from EA feedback that included higher-frequency information to guide a force-tracking task. Fourteen young and 14 older adults performed low-level static isometric force-tracking with visual guidance of typical visual feedback and EA feedback containing augmented high-frequency errors. Stabilogram diffusion analysis was used to characterize force fluctuation dynamics. Also, the discharge behaviors of motor units and pooled motor unit coherence were assessed following the decomposition of multi-channel surface electromyography (EMG). EA produced different behavioral and neurophysiological impacts on young and older adults. Older adults exhibited inferior task accuracy with EA feedback than with typical visual feedback, but not young adults. Although stabilogram diffusion analysis revealed that EA led to a significant decrease in critical time points for both groups, EA potentiated the critical point of force fluctuations <ΔFc2>, short-term effective diffusion coefficients (Ds), and short-term exponent scaling only for the older adults. Moreover, in older adults, EA added to the size of discharge variability of motor units and discharge regularity of cumulative discharge rate, but suppressed the pooled motor unit coherence in the 13–35 Hz band. Virtual EA alters the strategic balance between open-loop and closed-loop controls for force-tracking. Contrary to expectations, the prevailing use of closed-loop control with EA that contained high-frequency error information enhanced the motor unit discharge variability and undermined the force steadiness in the older group, concerning declines in physiological complexity in the neurobehavioral system and the common drive to the motoneuronal pool against force destabilization. PMID:29167637

Illness behavior.

PubMed

Sirri, Laura; Grandi, Silvana

2012-01-01

The term illness behavior was introduced by Mechanic and Volkart to describe the individuals' different ways to respond to their own health status. Pilowsky's concept of abnormal illness behavior encompasses several clinical conditions characterized by a maladaptive mode of experiencing, perceiving, evaluating and responding to one's own health status. The concept of somatization was criticized because it implies the presence of psychological distress or an underlying psychiatric disturbance when an organic cause for somatic symptoms is not found. Thus, more atheoretical terms , such as functional somatic symptoms and medically unexplained symptoms, were introduced. Both Kellner's Symptom Questionnaire and Derogatis' Symptom Checklist-90 include a scale for somatic symptoms, and other questionnaires were specifically designed to measure their frequency and severity. Kellner's Illness Attitude Scales appear to be the gold standard for the measurement of the hypochondriacal spectrum, which includes several clinical conditions, such as nosophobia, thanatophobia and health anxiety. The assessment of illness denial should consider that a certain degree of denial may sometimes prevent patients from overwhelming psychological distress resulting from life-threatening or stigmatized diseases. Denial may concern both physical and psychiatric symptoms. Specific instruments are available for both types of denial. The cognitive and emotional representations developed by subjects when they have to cope with an illness or a perceived health threat are subsumed under the concept of illness perception and may be assessed by the Brief Illness Perception Questionnaire. Copyright © 2012 S. Karger AG, Basel.

Mechanics of mouse ocular motor plant quantified by optogenetic techniques.

PubMed

Stahl, John S; Thumser, Zachary C; May, Paul J; Andrade, Francisco H; Anderson, Sean R; Dean, Paul

2015-09-01

Rigorous descriptions of ocular motor mechanics are often needed for models of ocular motor circuits. The mouse has become an important tool for ocular motor studies, yet most mechanical data come from larger species. Recordings of mouse abducens neurons indicate the mouse mechanics share basic viscoelastic properties with larger species but have considerably longer time constants. Time constants can also be extracted from the rate at which the eye re-centers when released from an eccentric position. The displacement can be accomplished by electrically stimulating ocular motor nuclei, but electrical stimulation may also activate nearby ocular motor circuitry. We achieved specific activation of abducens motoneurons through photostimulation in transgenic mice expressing channelrhodopsin in cholinergic neurons. Histology confirmed strong channelrhodopsin expression in the abducens nucleus with relatively little expression in nearby ocular motor structures. Stimulation was delivered as 20- to 1,000-ms pulses and 40-Hz trains. Relaxations were modeled best by a two-element viscoelastic system. Time constants were sensitive to stimulus duration. Analysis of isometric relaxation of isolated mouse extraocular muscles suggest the dependence is attributable to noninstantaneous decay of active forces in non-twitch fibers following stimulus offset. Time constants were several times longer than those obtained in primates, confirming that the mouse ocular motor mechanics are relatively sluggish. Finally, we explored the effects of 0.1- to 20-Hz sinusoidal photostimuli and demonstrated their potential usefulness in characterizing ocular motor mechanics, although this application will require further data on the temporal relationship between photostimulation and neuronal firing in extraocular motoneurons.

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Pastor, Angel M

2013-01-01

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might

Some verbal behavior about verbal behavior

PubMed Central

Salzinger, Kurt

2003-01-01

Beginning with behavior analysts' tendency to characterize verbal behavior as “mere” verbal behavior, the author reviews his own attempt to employ it to influence both his staff and policies of our government. He then describes its role in psychopathology, its effect on speakers in healing themselves and on engendering creativity. The paper ends by calling to our attention the role of verbal behavior in the construction of behavior analysis. PMID:22478393

Behavioral economics.

PubMed

Chambers, David W

2009-01-01

It is human nature to overestimate how rational we are, both in general and even when we are trying to be. Such irrationality is not random, and the search for and explanation of patterns of fuzzy thinking is the basis for a new academic discipline known as behavioral economics. Examples are given of some of the best understood of our foibles, including prospect theory, framing, anchoring, salience, confirmation bias, superstition, and ownership. Humans have two cognitive systems: one conscious, deliberate, slow, and rational; the other fast, pattern-based, emotionally tinged, and intuitive. Each is subject to its own kind of error. In the case of rational thought, we tend to exaggerate our capacity; for intuition, we fail to train it or recognize contexts where it is inappropriate. Humans are especially poor at estimating probabilities, or even understanding what they are. It is a common human failing to reason backwards from random outcomes that are favorable to beliefs about our power to predict the future. Five suggestions are offered for thinking within our means.

Applying Behavioral Conditioning to Identify Anticipatory Behaviors.

PubMed

Krebs, Bethany L; Torres, Erika; Chesney, Charlie; Kantoniemi Moon, Veronica; Watters, Jason V

2017-01-01

The ability to predict regular events can be adaptive for nonhuman animals living in an otherwise unpredictable environment. Animals may exhibit behavioral changes preceding a predictable event; such changes reflect anticipatory behavior. Anticipatory behavior is broadly defined as a goal-directed increase in activity preceding a predictable event and can be useful for assessing well being in animals in captivity. Anticipation may look different in different animals, however, necessitating methods to generate and study anticipatory behaviors across species. This article includes a proposed method for generating and describing anticipatory behavior in zoos using behavioral conditioning. The article also includes discussion of case studies of the proposed method with 2 animals at the San Francisco Zoo: a silverback gorilla (Gorilla gorilla gorilla) and a red panda (Ailurus fulgens). The study evidence supports anticipation in both animals. As behavioral conditioning can be used with many animals, the proposed method provides a practical approach for using anticipatory behavior to assess animal well being in zoos.

The Necessity of "Behaviorism."

ERIC Educational Resources Information Center

Schoenfeld, William N.

1993-01-01

Discusses the theory of behaviorism from a psychological perspective. Three issues are addressed: (1) the datum, including human verbal behavior; (2) the behavior stream; and (3) reduction, including a scientific viewpoint. (Contains two references.) (LRW)

Human behavior and malaria.

PubMed

Hongvivatana, T

1986-09-01

Human behavior in malaria is often narrowly referred to behavior of the target populations in transmission and control of malaria. In this presentation it was discussed that such view is too narrow. A broader framework incorporating illness behavior and human behavior in malaria control bureaucracies is needed for the success of national malaria control programme. Literature under the three broad categories of human behavior in malaria is reviewed to justify future directions in human behavior research and their significance for successful malaria control.

Fire Behavior (FB)

Treesearch

Robert E. Keane

2006-01-01

The Fire Behavior (FB) method is used to describe the behavior of the fire and the ambient weather and fuel conditions that influence the fire behavior. Fire behavior methods are not plot based and are collected by fire event and time-date. In general, the fire behavior data are used to interpret the fire effects documented in the plot-level sampling. Unlike the other...

Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury

PubMed Central

Lee, Kun-Ze; Dougherty, Brendan J.; Sandhu, Milapjit S.; Lane, Michael A.; Reier, Paul J.; Fuller, David D.

2013-01-01

Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8 wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths*min−1) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. PMID:23954215

Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

NASA Technical Reports Server (NTRS)

Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

2002-01-01

The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

Computational Analysis of Behavior.

PubMed

Egnor, S E Roian; Branson, Kristin

2016-07-08

In this review, we discuss the emerging field of computational behavioral analysis-the use of modern methods from computer science and engineering to quantitatively measure animal behavior. We discuss aspects of experiment design important to both obtaining biologically relevant behavioral data and enabling the use of machine vision and learning techniques for automation. These two goals are often in conflict. Restraining or restricting the environment of the animal can simplify automatic behavior quantification, but it can also degrade the quality or alter important aspects of behavior. To enable biologists to design experiments to obtain better behavioral measurements, and computer scientists to pinpoint fruitful directions for algorithm improvement, we review known effects of artificial manipulation of the animal on behavior. We also review machine vision and learning techniques for tracking, feature extraction, automated behavior classification, and automated behavior discovery, the assumptions they make, and the types of data they work best with.

Behavior Management: Examining the Functions of Behavior

ERIC Educational Resources Information Center

Alstot, Andrew E.; Alstot, Crystal D.

2015-01-01

Appropriate student behavior is essential for the success of a physical education lesson. Despite using effective proactive management strategies, teachers may need to also use reactive techniques to reduce problem behaviors by applying suitable consequences. For these consequences to be effective, they must be aligned with the function, or cause,…

Genes and Social Behavior

PubMed Central

Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

2011-01-01

What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

Moving Forward: Positive Behavior Support and Applied Behavior Analysis

ERIC Educational Resources Information Center

Tincani, Matt

2007-01-01

A controversy has emerged about the relationship between positive behavior support and applied behavior analysis. Some behavior analysts suggest that positive behavior support and applied behavior analysis are the same (e.g., Carr & Sidener, 2002). Others argue that positive behavior support is harmful to applied behavior analysis (e.g., Johnston,…

MEASUREMENT OF BEHAVIORAL THERMOREGULATION

EPA Science Inventory

The measurement of thermoregulatory behavior by the techniques of thermal gradient and operant conditioning allows the study of many parameters of the behavioral control of body temperature in particular species as well as the comparative study of thermo- regulatory capabilities ...

Behavior Modification in Coaching.

ERIC Educational Resources Information Center

Lynch, Annette Rutt; Stillman, Stephen M.

1979-01-01

An example of behavior modification used in athletic coaching is presented. The case study involves a member of a women's basketball team and details the use of behavior modification for both weight reduction and skill improvement. (JMF)

Behavioral Assessment: Questionnaires.

ERIC Educational Resources Information Center

Wilson, C. Chrisman

1980-01-01

This is a general discussion of the validity, reliability, function, and format of questionnaires designed to measure problem behavior, noncompliance, anxiety, social interaction, hyperactivity, drug use, and sexual behavior. Commonly used questionnaires are cited. (CP)

Child Behavior Disorders

MedlinePlus

... a death in the family may cause a child to act out. Behavior disorders are more serious. ... The behavior is also not appropriate for the child's age. Warning signs can include Harming or threatening ...

Learning and Behavior

MedlinePlus

... Aggression Sensory Processing Disorder Social Interactions Book: The Psychology of Duchenne (download) Guide: Learning & Behavior (download) Home ❯ ... a teen and adult. Additional Resources Book: The Psychology of Duchenne (download) Education Matters Guide: Learning & Behavior ( ...

Positive Behavior Support and Applied Behavior Analysis

PubMed Central

Johnston, J.M; Foxx, Richard M; Jacobson, John W; Green, Gina; Mulick, James A

2006-01-01

This article reviews the origins and characteristics of the positive behavior support (PBS) movement and examines those features in the context of the field of applied behavior analysis (ABA). We raise a number of concerns about PBS as an approach to delivery of behavioral services and its impact on how ABA is viewed by those in human services. We also consider the features of PBS that have facilitated its broad dissemination and how ABA might benefit from emulating certain practices of the PBS movement. PMID:22478452

Behavioral Objectives for English

ERIC Educational Resources Information Center

Zoellner, Robert

1972-01-01

A review-critique of On Writing Behavioral Objectives for English, by John Maxwell and Anthony Lovat, in which behavioral objectives theory is dominated by a stimulus-response rather than a stimulus-response-reinforcement psychology. The reviewer questions whether behavioral objectives can be applied accurately and without distortion of meanings,…

Knowledge, Understanding, and Behavior

DTIC Science & Technology

2003-10-04

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP021346 TITLE: Knowledge , Understanding , and Behavior DISTRIBUTION... Knowledge , Understanding , and Behavior James Albus Intelligent Systems Division , National Institute of Standards and Technology, Gaithersburg, MD 20899 301... understanding ? How does understanding the world works, and knowledge of procedures for using influence behavior? These are philosophical questions models to

Bad Behavior: Improving Reproducibility in Behavior Testing.

PubMed

Andrews, Anne M; Cheng, Xinyi; Altieri, Stefanie C; Yang, Hongyan

2018-01-24

Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.

Safety Behaviors and Stuttering.

PubMed

Lowe, Robyn; Helgadottir, Fjola; Menzies, Ross; Heard, Rob; O'Brian, Sue; Packman, Ann; Onslow, Mark

2017-05-24

Those who are socially anxious may use safety behaviors during feared social interactions to prevent negative outcomes. Safety behaviors are associated with anxiety maintenance and poorer treatment outcomes because they prevent fear extinction. Social anxiety disorder is often comorbid with stuttering. Speech pathologists reported in a recent publication (Helgadottir, Menzies, Onslow, Packman, & O'Brian, 2014a) that they often recommended procedures for clients that could be safety behaviors. This study investigated the self-reported use of safety behaviors by adults who stutter. Participants were 133 adults who stutter enrolled in an online cognitive-behavior therapy program. Participants completed a questionnaire about their use of potential safety behaviors when anxious during social encounters. Correlations were computed between safety behaviors and pretreatment scores on measures of fear of negative evaluation and negative cognitions. Of 133 participants, 132 reported that they used safety behaviors. Many of the safety behaviors correlated with higher scores for fear of negative evaluation and negative cognitions. Adults who stutter report using safety behaviors, and their use is associated with pretreatment fear of negative evaluation and unhelpful thoughts about stuttering. These results suggest that the negative effects of safety behaviors may extend to those who stutter, and further research is needed.

Behavioral Immunity in Insects

PubMed Central

de Roode, Jacobus C.; Lefèvre, Thierry

2012-01-01

Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied. PMID:26466629

Analysis of Autopilot Behavior

NASA Technical Reports Server (NTRS)

Sherry, Lance; Polson, Peter; Feay, Mike; Palmer, Everett; Null, Cynthia H. (Technical Monitor)

1998-01-01

Aviation and cognitive science researchers have identified situations in which the pilot's expectations for behavior of autopilot avionics are not matched by the actual behavior of the avionics. These "automation surprises" have been attributed to differences between the pilot's model of the behavior of the avionics and the actual behavior encoded in the avionics software. A formal technique is described for the analysis and measurement of the behavior of the cruise pitch modes of a modern Autopilot. The analysis characterizes the behavior of the Autopilot as situation-action rules. The behavior of the cruise pitch mode logic for a contemporary modern Autopilot was found to include 177 rules, including Level Change (23), Vertical Speed (16), Altitude Capture (50), and Altitude Hold (88). These rules are determined based on the values of 62 inputs. Analysis of the rule-based model also shed light on the factors cited in the literature as contributors to "automation surprises."

Understanding the extraocular muscles and oculomotor, trochlear, and abducens nerves through a simulation in physical examination training: an innovative approach.

PubMed

Zhang, Niu; He, Xiaohua

2010-01-01

The purpose of this study was to investigate the effect of an innovative exhibitory eye model simulation in a physical examination laboratory format on explaining Listing's Law concerning the individual extraocular muscle action and the rationale for cranial nerve testing. Participants were 71 volunteers in the third quarter of a chiropractic training program. The study involved a specially designed eyeball model used to explain the movements of individual extraocular muscles based on Listing's law and their cranial innervations in conjunction with the physical examination. Pre- and post-written tests were used to assess participants' understanding of the subjects taught. The test results were compared with those of nonparticipants who also took the same pre- and posttests. An independent samples t-test of the posttest showed a significant difference between the groups. The study group students achieved higher scores than their counterparts in the control group. Using an innovative approach to explain Listing's law and rationale for cranial nerve tests can improve physical examination skill and help produce more effective written test results.

Introduction to behavioral addictions.

PubMed

Grant, Jon E; Potenza, Marc N; Weinstein, Aviv; Gorelick, David A

2010-09-01

Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persistent behavior, despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have historically been conceptualized in several ways. One view posits these disorders as lying along an impulsive-compulsive spectrum, with some classified as impulse control disorders. An alternate, but not mutually exclusive, conceptualization considers the disorders as non-substance or "behavioral" addictions. Inform the discussion on the relationship between psychoactive substance and behavioral addictions. We review data illustrating similarities and differences between impulse control disorders or behavioral addictions and substance addictions. This topic is particularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natural history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiological mechanisms, and response to treatment, supporting the DSM-V Task Force proposed new category of Addiction and Related Disorders encompassing both substance use disorders and non-substance addictions. Current data suggest that this combined category may be appropriate for pathological gambling and a few other better studied behavioral addictions, e.g., Internet addiction. There is currently insufficient data to justify any classification of other proposed behavioral addictions. Proper categorization of behavioral addictions or impulse control disorders has substantial implications for the development of improved prevention and treatment strategies.

Behavioral and Neural Adaptation in Approach Behavior.

PubMed

Wang, Shuo; Falvello, Virginia; Porter, Jenny; Said, Christopher P; Todorov, Alexander

2018-06-01

People often make approachability decisions based on perceived facial trustworthiness. However, it remains unclear how people learn trustworthiness from a population of faces and whether this learning influences their approachability decisions. Here we investigated the neural underpinning of approach behavior and tested two important hypotheses: whether the amygdala adapts to different trustworthiness ranges and whether the amygdala is modulated by task instructions and evaluative goals. We showed that participants adapted to the stimulus range of perceived trustworthiness when making approach decisions and that these decisions were further modulated by the social context. The right amygdala showed both linear response and quadratic response to trustworthiness level, as observed in prior studies. Notably, the amygdala's response to trustworthiness was not modulated by stimulus range or social context, a possible neural dynamic adaptation. Together, our data have revealed a robust behavioral adaptation to different trustworthiness ranges as well as a neural substrate underlying approach behavior based on perceived facial trustworthiness.

Sociopathic behavior and dementia.

PubMed

Cipriani, Gabriele; Borin, Gemma; Vedovello, Marcella; Di Fiorino, Andrea; Nuti, Angelo

2013-06-01

The maintenance of appropriate social behavior is a very complex process with many contributing factors. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. Damage to these systems may lead to distinct social behavior abnormalities. When patients present with dysmoral behavior for the first time, as a change from a prior pervasive pattern of behavior, clinicians need to consider a possible, causative brain disorder. The aim is to explore sociopathy as a manifestation of dementia. We searched electronic databases and key journals for original research and review articles on sociopathy in demented patients using the search terms "sociopathy, acquired sociopathy, sociopathic behavior, dementia, and personality". In conclusion, dementia onset may be heralded by changes in personality including alteration in social interpersonal behavior, personal regulation, and empathy. The sociopathy of dementia differs from antisocial/psychopathic personality disorders.

[Addictive behavior disorders].

PubMed

Masaki, Daiki; Tsuchida, Hideto; Kitabayashi, Yurinosuke; Tani, Naosuke; Fukui, Kenji

2007-10-01

"Addiction" used to remind anyone of the use or abuse of chemical substances. In recent years, however, researchers and clinicians have begun to classify other excessive behaviors including gambling, eating shopping and self-injury into the addictive behavior. Above all, pathological gambling and bulimia nervosa patients often make trouble for psychiatrists and psychologists, not only for their family. On the other hand, the neural substrata underlying substance dependence have been revealed. Especially, it is implicated that the mesolimbic neuron plays a crucial role on the reward system. The recent studies suggest that reduced activation of the reward system might be related to the addictive behaviors such as pathological gambling, binge eating and sexual behavior. Further biological researches about the addictive behavior would help our deeper understanding of its disorders. As to the pharmacotherapy, many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating the addictive behaviors.

Behavior dynamics: One perspective

PubMed Central

Marr, M. Jackson

1992-01-01

Behavior dynamics is a field devoted to analytic descriptions of behavior change. A principal source of both models and methods for these descriptions is found in physics. This approach is an extension of a long conceptual association between behavior analysis and physics. A theme common to both is the role of molar versus molecular events in description and prediction. Similarities and differences in how these events are treated are discussed. Two examples are presented that illustrate possible correspondence between mechanical and behavioral systems. The first demonstrates the use of a mechanical model to describe the molar properties of behavior under changing reinforcement conditions. The second, dealing with some features of concurrent schedules, focuses on the possible utility of nonlinear dynamical systems to the description of both molar and molecular behavioral events as the outcome of a deterministic, but chaotic, process. PMID:16812655

Fetal behavioral teratology.

PubMed

Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

2010-10-01

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Cognitive-Behavioral Therapy.

PubMed

An, Hong; He, Ri-Hui; Zheng, Yun-Rong; Tao, Ran

2017-01-01

Cognitive-behavioral therapy (CBT) is the main method of psychotherapy generally accepted in the field of substance addiction and non-substance addiction. This chapter mainly introduces the methods and technology of cognitive-behavior therapy of substance addiction, especially in order to prevent relapse. In the cognitive-behavior treatment of non-substance addiction, this chapter mainly introduces gambling addiction and food addiction.

BEHAVIOR THERAPY FOR TRANSSEXUALISM

PubMed Central

Andrade, A. Chitra; Kumaraiah, V.; Mishra, H.; Chatterji, S.; Andrade, Chittaranjan

1995-01-01

Transsexualism is a rare disorder, and there is little literature available on its treatment. A case is presented of transsexualism with homosexual orientation in a 24 year old male. Since the disorder appeared to have behavioral antecedents, it was treated with a behavior therapy package comprising relaxation, aversion therapy with aversion relief, modelling, hypnosis, orgasmic reconditioning, behavioral counselling and sex education. Therapy resulted in normalization of gender identity, but the homosexual orientation persisted. PMID:21743738

Suicide and Suicidal Behavior

PubMed Central

Nock, Matthew K.; Borges, Guilherme; Bromet, Evelyn J.; Cha, Christine B.; Kessler, Ronald C.; Lee, Sing

2008-01-01

Suicidal behavior is a leading cause of injury and death worldwide. Information about the epidemiology of such behavior is important for policy-making and prevention. The authors reviewed government data on suicide and suicidal behavior and conducted a systematic review of studies on the epidemiology of suicide published from 1997 to 2007. The authors' aims were to examine the prevalence of, trends in, and risk and protective factors for suicidal behavior in the United States and cross-nationally. The data revealed significant cross-national variability in the prevalence of suicidal behavior but consistency in age of onset, transition probabilities, and key risk factors. Suicide is more prevalent among men, whereas nonfatal suicidal behaviors are more prevalent among women and persons who are young, are unmarried, or have a psychiatric disorder. Despite an increase in the treatment of suicidal persons over the past decade, incidence rates of suicidal behavior have remained largely unchanged. Most epidemiologic research on suicidal behavior has focused on patterns and correlates of prevalence. The next generation of studies must examine synergistic effects among modifiable risk and protective factors. New studies must incorporate recent advances in survey methods and clinical assessment. Results should be used in ongoing efforts to decrease the significant loss of life caused by suicidal behavior. PMID:18653727

Behavioral economics without anomalies.

PubMed Central

Rachlin, H

1995-01-01

Behavioral economics is often conceived as the study of anomalies superimposed on a rational system. As research has progressed, anomalies have multiplied until little is left of rationality. Another conception of behavioral economics is based on the axiom that value is always maximized. It incorporates so-called anomalies either as conflicts between temporal patterns of behavior and the individual acts comprising those patterns or as outcomes of nonexponential time discounting. This second conception of behavioral economics is both empirically based and internally consistent. PMID:8551195

Rule-governed behavior and behavioral anthropology

PubMed Central

Malott, Richard W.

1988-01-01

According to cultural materialism, cultural practices result from the materialistic outcomes of those practices, not from sociobiological, mentalistic, or mystical predispositions (e.g., Hindus worship cows because, in the long run, that worship results in more food, not less food). However, according to behavior analysis, such materialistic outcomes do not reinforce or punish the cultural practices, because such outcomes are too delayed, too improbable, or individually too small to directly reinforce or punish the cultural practices (e.g., the food increase is too delayed to reinforce the cow worship). Therefore, the molar, materialistic contingencies need the support of molecular, behavioral contingencies. And according to the present theory of rule-governed behavior, the statement of rules describing those molar, materialistic contingencies can establish the needed molecular contingencies. Given the proper behavioral history, such rule statements combine with noncompliance to produce a learned aversive condition (often labeled fear, anxiety, or guilt). The termination of this aversive condition reinforces compliance, just as its presentation punishes noncompliance (e.g., the termination of guilt reinforces the tending to a sick cow). In addition, supernatural rules often supplement these materialistic rules. Furthermore, the production of both materialistic and supernatural rules needs cultural designers who understand the molar, materialistic contingencies. PMID:22478012

Safety Behaviors and Stuttering

ERIC Educational Resources Information Center

Lowe, Robyn; Helgadottir, Fjola; Menzies, Ross; Heard, Rob; O'Brian, Sue; Packman, Ann; Onslow, Mark

2017-01-01

Purpose: Those who are socially anxious may use safety behaviors during feared social interactions to prevent negative outcomes. Safety behaviors are associated with anxiety maintenance and poorer treatment outcomes because they prevent fear extinction. Social anxiety disorder is often comorbid with stuttering. Speech pathologists reported in a…

Adolescents' Demonstrative Behavior Research

ERIC Educational Resources Information Center

Parfilova, Gulfiya G.; Karimova, Lilia Sh.

2016-01-01

The problem of demonstrative behavior is very topical among teenagers and this issue has become the subject of systematic scientific research. Demonstrative manifestations in adolescents disrupt the favorable socialization; therefore, understanding, prevention and correction of demonstrative behavior at this age is relevant and requires special…

Explaining Human Behavior.

ERIC Educational Resources Information Center

Olson, Alton T.; And Others

The Deductive-Nomological (D-N) model of human behavior is useful and provides the most objective explanation when it is appropriate but it is not necessarily an all-inclusive statement. For instance, explaining human behavior is always an act that entails languages and theories that are value laden and reveal human choices; however the D-N model…

Zen and Behavior Analysis

ERIC Educational Resources Information Center

Bass, Roger

2010-01-01

Zen's challenge for behavior analysis is to explain a repertoire that renders analysis itself meaningless--a result following not from scientific or philosophical arguments but rather from a unique verbal history generated by Zen's methods. Untying Zen's verbal knots suggests how meditation's and koans' effects on verbal behavior contribute to…

The Behavior Analysis Classroom.

ERIC Educational Resources Information Center

Bushell, Don, Jr.

In a Behavior Analysis classroom the first step is to define instructional objectives for academic or social skills. The second step is to determine how much the child already knows about what is to be taught. An Entry Behavior Inventory and diagnostic tests help teachers decide where each child needs to begin working in the sequence leading to…

Health Behaviors of Psychotherapists.

ERIC Educational Resources Information Center

Royak-Schaler, Renee; Feldman, Robert H. L.

1984-01-01

Examined the health behaviors practiced by psychotherapists (N=86) themselves and the extent to which they focus on these behaviors with their clients. Results indicated that psychotherapists actively evaluate and make recommendations to their clients in the areas of diet, physical exercise, and relaxation practice. (JAC)

Testosterone and Social Behavior

ERIC Educational Resources Information Center

Booth, Alan; Granger, Douglas A.; Mazur, Allan; Kivlighan, Katie T.

2006-01-01

Popular perceptions of the effect of testosterone on "manly" behavior are inaccurate. We need to move away from such simplistic notions by treating testosterone as one component along with other physiological, psychological and sociological variables in interactive and reciprocal models of behavior. Several hormones can now be measured in saliva,…

Professors' Irritating Behavior Study

ERIC Educational Resources Information Center

Malikow, Max

2007-01-01

The purpose of this study was to quantify the irritating behaviors of professors as experienced and reported by 232 Le Moyne College students. In this study, "irritating behavior" was understood as "actions that vex, annoy, bother, pester, frustrate, or provoke anger." The survey used in this study was developed by Larry M. Ludewig, Ph.D.,…

Behavior, Expectations and Status

ERIC Educational Resources Information Center

Webster, Jr, Murray; Rashotte, Lisa Slattery

2010-01-01

We predict effects of behavior patterns and status on performance expectations and group inequality using an integrated theory developed by Fisek, Berger and Norman (1991). We next test those predictions using new experimental techniques we developed to control behavior patterns as independent variables. In a 10-condition experiment, predictions…

Nascent Leadership Behaviors

ERIC Educational Resources Information Center

Payette, Dennis L.; Libertella, Anthony F.

2011-01-01

This paper is a compendium of leadership behaviors that emerging or aspirant leaders could choose to enhance their management and leadership skills. These behaviors were drawn directly from the experience of the authors, both of whom have held senior leadership and management positions in business, law, and higher education. This paper is an…

Behavior Analysis: Methodological Foundations.

ERIC Educational Resources Information Center

Owen, James L.

Behavior analysis provides a unique way of coming to understand intrapersonal and interpersonal communication behaviors, and focuses on control techniques available to a speaker and counter-control techniques available to a listener. "Time-series methodology" is a convenient term because it subsumes under one label a variety of baseline…

Symbiotic Optimization of Behavior

DTIC Science & Technology

2015-05-01

SYMBIOTIC OPTIMIZATION OF BEHAVIOR UNIVERSITY OF WASHINGTON MAY 2015 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED...2014 4. TITLE AND SUBTITLE SYMBIOTIC OPTIMIZATION OF BEHAVIOR 5a. CONTRACT NUMBER FA8750-12-1-0304 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT

Stability of Aggressive Behavior.

ERIC Educational Resources Information Center

Eron, Leonard D.; Huesmann, L. Rowell

As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

Behavior Therapy of Impotence

ERIC Educational Resources Information Center

Dengrove, Edward

1971-01-01

Behavior therapy approaches to the treatment of male sexual impotence, specifically premature ejaculation and erective impotence, are discussed. Included in the behavioral therapies are systematic desensitization, active graded therapy, assertive techniques, sexual responses, operant approaches and others. Often marriage counseling is also…

Personalizing Behavior Modification.

ERIC Educational Resources Information Center

White, Debra G.; And Others

1987-01-01

Process reinforcement is proposed as a reinforcement method that is more comfortable, personal, comprehensive, and interactive than traditional behavior modification. Process reinforcement strengthens desired behaviors by engaging learners in a one-on-one examination of how they achieved correct responses and by practicing comfortable eye contact…

Health Behavior in Hypochondriasis.

PubMed

Schwind, Julia; Neng, Julia M B; Höfling, Volkmar; Weck, Florian

2015-07-01

The relationship between health behavior and hypochondriasis has not yet been sufficiently examined, as previous studies investigated only individual dimensions of health behavior. In the present study, we extend current literature by examining multiple dimensions of health behavior. One hundred twenty-six participants, consisting of 40 participants with a primary diagnosis of hypochondriasis, 41 participants with a primary diagnosis of anxiety disorder, and 45 healthy controls, completed a multidimensional questionnaire for the assessment of health behavior and other measures for the evaluation of general psychopathology, illness anxiety, depression, and general anxiety. Patients with hypochondriasis revealed a less active way of life (d = 0.89) and lower hygiene (d = 0.60) than healthy controls, but did not differ from healthy controls regarding their compliance to medical recommendations. No differences were found in substance avoidance, security orientation, and diet. Hypochondriasis-specific behavior should be monitored in the treatment of the disorder.

Towards Behavioral Reflexion Models

NASA Technical Reports Server (NTRS)

Ackermann, Christopher; Lindvall, Mikael; Cleaveland, Rance

2009-01-01

Software architecture has become essential in the struggle to manage today s increasingly large and complex systems. Software architecture views are created to capture important system characteristics on an abstract and, thus, comprehensible level. As the system is implemented and later maintained, it often deviates from the original design specification. Such deviations can have implication for the quality of the system, such as reliability, security, and maintainability. Software architecture compliance checking approaches, such as the reflexion model technique, have been proposed to address this issue by comparing the implementation to a model of the systems architecture design. However, architecture compliance checking approaches focus solely on structural characteristics and ignore behavioral conformance. This is especially an issue in Systems-of- Systems. Systems-of-Systems (SoS) are decompositions of large systems, into smaller systems for the sake of flexibility. Deviations of the implementation to its behavioral design often reduce the reliability of the entire SoS. An approach is needed that supports the reasoning about behavioral conformance on architecture level. In order to address this issue, we have developed an approach for comparing the implementation of a SoS to an architecture model of its behavioral design. The approach follows the idea of reflexion models and adopts it to support the compliance checking of behaviors. In this paper, we focus on sequencing properties as they play an important role in many SoS. Sequencing deviations potentially have a severe impact on the SoS correctness and qualities. The desired behavioral specification is defined in UML sequence diagram notation and behaviors are extracted from the SoS implementation. The behaviors are then mapped to the model of the desired behavior and the two are compared. Finally, a reflexion model is constructed that shows the deviations between behavioral design and implementation. This

How research in behavioral pharmacology informs behavioral science.

PubMed

Branch, Marc N

2006-05-01

Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its conceptualizations and theory. In this article, I outline three general strategies in behavioral pharmacology research that have been employed to increase understanding of behavioral processes. Examples are provided of the general characteristics of the strategies and of implications of previous research for behavior theory. Behavior analysis will advance as its theories are challenged.

How Research in Behavioral Pharmacology Informs Behavioral Science

ERIC Educational Resources Information Center

Branch, Marc N.

2006-01-01

Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its…

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters.

PubMed

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E

2009-09-20

The sense of taste is crucial in an animal's determination as to what is edible and what is not. This gustatory function is especially important in goldfish, who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe, which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons that have radially directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca(++)-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3-hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediate neurotransmission between reflex interneurons and vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system.

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish Cellular organization and neurotransmitters

PubMed Central

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E.

2009-01-01

The sense of taste is crucial in an animal’s determination as to what is edible and what is not. This gustatory function is especially important in goldfish who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons which have radially-directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca++-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (±)-α-amino-3-hydroxy-5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediates neurotransmission between reflex interneurons and vagal motoneurons. Thus the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system. PMID:19598285

Alcohol and risky behaviors.

PubMed

Corte, Colleen M; Sommers, Marilyn Sawyer

2005-01-01

The purpose of this chapter is to review and critique the literature on risky drinking, driving, and sexual behaviors. To complete this review, electronic searches using databases from the disciplines of nursing, medicine, and psychology were used with keywords alcohol and risky behavior, risky drinking, risky driving, risky sex, and sexual aggression, as well as other relevant terms. The basic tenets of contemporary theoretical models of risky behaviors are used as a framework for reviewing the literature. Most relevant to the discussion are the relationships among the behaviors, risk and protective factors, and major unresolved theoretical and methodological issues. In the literature, sensation seeking was differentially associated with risky drinking, driving, and sex, but causal assertions are premature. Important conceptual and physiological issues are clarified. First, unconventionality contributes to risky drinking, risky driving, and, among adolescents, risky sex. Second, the pharmacologic effects of alcohol on cognitive processing contribute to risky sex, but only among persons who feel conflicted about risky sex (e.g., condom use). This perception may be particularly true for men who have a belief that alcohol will enhance sex. Third, sexual aggression appears to stem from a variety of factors, including the pharmacologic effects of alcohol on aggression and stereotypes about drinking women. Exploration of risk and protective factors adds breadth and depth to the discussion of risk taking. Risk factors include (1) high tolerance for deviance, (2) unconventional attitudes and behaviors such as early alcohol use and precocious sex, (3) peer norms for deviance, (4) high sensation seeking, and, to a lesser extent, (5) disturbed risk perception and positive beliefs about alcohol. Protective factors appear to mitigate risk and include (1) conventional attitudes and behaviors and (2) having peers that model conventional attitudes and behaviors. Although

Introduction to Behavioral Addictions

PubMed Central

Grant, Jon E.; Potenza, Marc N.; Weinstein, Aviv; Gorelick, David A.

2011-01-01

Background Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persistent behavior despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have historically been conceptualized in several ways. One view posits these disorders as lying along an impulsive-compulsive spectrum, with some classified as impulse control disorders. An alternate, but not mutually exclusive, conceptualization considers the disorders as non-substance or “behavioral” addictions. Objectives Inform the discussion on the relationship between psychoactive substance and behavioral addictions. Methods: We review data illustrating similarities and differences between impulse control disorders or behavioral addictions and substance addictions. This topic is particularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Results Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natural history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiological mechanisms, and response to treatment, supporting the DSM-V Task Force proposed new category of Addiction and Related Disorders encompassing both substance use disorders and non-substance addictions. Current data suggest that this combined category may be appropriate for pathological gambling and a few other better studied behavioral addictions, e.g., Internet addiction. There is currently insufficient data to justify any classification of other proposed behavioral addictions. Conclusions and Scientific Significance Proper categorization of behavioral addictions or impulse control disorders has substantial implications for the development of improved prevention and treatment strategies. PMID:20560821

On operator strategic behavior

NASA Technical Reports Server (NTRS)

Hancock, P. A.

1991-01-01

Deeper and more detailed knowledge as to how human operators such as pilots respond, singly and in groups, to demands on their performance which arise from technical systems will support the manipulation of such systems' design in order to accommodate the foibles of human behavior. Efforts to understand how self-autonomy impacts strategic behavior and such related issues as error generation/recognition/correction are still in their infancy. The present treatment offers both general and aviation-specific definitions of strategic behavior as precursors of prospective investigations.

Behavioral Health Program Element

NASA Technical Reports Server (NTRS)

Leveton, Lauren B.

2006-01-01

The project goal is to develop behavioral health prevention and maintenance system for continued crew health, safety, and performance for exploration missions. The basic scope includes a) Operationally-relevant research related to clinical cognitive and behavioral health of crewmembers; b) Ground-based studies using analog environments (Antarctic, NEEMO, simulations, and other testbeds; c) ISS studies (ISSMP) focusing on operational issues related to behavioral health outcomes and standards; d) Technology development activities for monitoring and diagnostic tools; and e) Cross-disciplinary research (e.g., human factors and habitability research, skeletal muscle, radiation).

Invitation to Consumer Behavior Analysis

ERIC Educational Resources Information Center

Foxall, Gordon R.

2010-01-01

This article presents an introduction to consumer behavior analysis by describing the Behavioral Perspective Model of consumer choice and showing how research has, first, confirmed this framework and, second, opened up behavior analysis and behavioral economics to the study of consumer behavior in natural settings. It concludes with a discussion…

Mechanisms of behavior modification in clinical behavioral medicine in China.

PubMed

Yang, Zhiyin; Su, Zhonghua; Ji, Feng; Zhu, Min; Bai, Bo

2014-08-01

Behavior modification, as the core of clinical behavioral medicine, is often used in clinical settings. We seek to summarize behavior modification techniques that are commonly used in clinical practice of behavioral medicine in China and discuss possible biobehavioral mechanisms. We reviewed common behavior modification techniques in clinical settings in China, and we reviewed studies that explored possible biobehavioral mechanisms. Commonly used clinical approaches of behavior modification in China include behavior therapy, cognitive therapy, cognitive-behavioral therapy, health education, behavior management, behavioral relaxation training, stress management intervention, desensitization therapy, biofeedback therapy, and music therapy. These techniques have been applied in the clinical treatment of a variety of diseases, such as chronic diseases, psychosomatic diseases, and psychological disorders. The biobehavioral mechanisms of these techniques involve the autonomic nervous system, neuroendocrine system, neurobiochemistry, and neuroplasticity. Behavior modification techniques are commonly used in the treatment of a variety of somatic and psychological disorders in China. Multiple biobehavioral mechanisms are involved in successful behavior modification.

Experiments in Animal Behavior

ERIC Educational Resources Information Center

Polt, James M.

1971-01-01

Describes experiments in conditioning, sensory processes, social behavior, imprinting, innate preferences for color and form, and discrimination learning suitable for secondary school students. Mealworms, crickets, and chicks are used as subjects. (AL)

Inelastic column behavior

NASA Technical Reports Server (NTRS)

Duberg, John E; Wilder, Thomas W , III

1952-01-01

The significant findings of a theoretical study of column behavior in the plastic stress range are presented. When the behavior of a straight column is regarded as the limiting behavior of an imperfect column as the initial imperfection (lack of straightness) approaches zero, the departure from the straight configuration occurs at the tangent-modulus load. Without such a concept of the behavior of a straight column, one is led to the unrealistic conclusion that lateral deflection of the column can begin at any load between the tangent-modulus value and the Euler load, based on the original elastic modulus. A family of curves showing load against lateral deflection is presented for idealized h-section columns of various lengths and of various materials that have a systematic variation of their stress-strain curves.

Normal Child Behavior

MedlinePlus

... that they are embarrassed by in public. The parents' own temperament, usual mood, and daily pressures will also influence how they interpret the child's behavior. Easygoing parents may accept a wider range ...

Monthly fire behavior patterns

Treesearch

Mark J. Schroeder; Craig C. Chandler

1966-01-01

From tabulated frequency distributions of fire danger indexes for a nationwide network of 89 stations, the probabilities of four types of fire behavior ranging from 'fire out' to 'critical' were calculated for each month and are shown in map form.

Driver behavior in traffic.

DOT National Transportation Integrated Search

2012-02-01

Existing traffic analysis and management tools do not model the ability of drivers to recognize their environment and respond to it with behaviors that vary according to the encountered driving situation. The small body of literature on characterizin...

Sensation during Active Behaviors

PubMed Central

Cardin, Jessica A.; Chiappe, M. Eugenia; Halassa, Michael M.; McGinley, Matthew J.; Yamashita, Takayuki

2017-01-01

A substantial portion of our sensory experience happens during active behaviors such as walking around or paying attention. How do sensory systems work during such behaviors? Neural processing in sensory systems can be shaped by behavior in multiple ways ranging from a modulation of responsiveness or sharpening of tuning to a dynamic change of response properties or functional connectivity. Here, we review recent findings on the modulation of sensory processing during active behaviors in different systems: insect vision, rodent thalamus, and rodent sensory cortices. We discuss the circuit-level mechanisms that might lead to these modulations and their potential role in sensory function. Finally, we highlight the open questions and future perspectives of this exciting new field. PMID:29118211

Francis Bacon's behavioral psychology.

PubMed

MacDonald, Paul S

2007-01-01

Francis Bacon offers two accounts of the nature and function of the human mind: one is a medical-physical account of the composition and operation of spirits specific to human beings, the other is a behavioral account of the character and activities of individual persons. The medical-physical account is a run-of-the-mill version of the late Renaissance model of elemental constituents and humoral temperaments. The other, less well-known, behavioral account represents an unusual position in early modern philosophy. This theory espouses a form of behavioral psychology according to which (a) supposed mental properties are "hidden forms" best described in dispositional terms, (b) the true character of an individual can be discovered in his observable behavior, and (c) an "informed" understanding of these properties permits the prediction and control of human behavior. Both of Bacon's theories of human nature fall under his general notion of systematic science: his medical-physical theory of vital spirits is theoretical natural philosophy and his behavioral theory of disposition and expression is operative natural philosophy. Because natural philosophy as a whole is "the inquiry of causes and the production of effects," knowledge of human nature falls under the same two-part definition. It is an inquisition of forms that pertains to the patterns of minute motions in the vital spirits and the production of effects that pertains both to the way these hidden motions produce behavioral effects and to the way in which a skillful agent is able to produce desired effects in other persons' behavior. (c) 2007 Wiley Periodicals, Inc.

Behavioral genetics and taste

PubMed Central

Boughter, John D; Bachmanov, Alexander A

2007-01-01

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste. PMID:17903279

Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout Muscle Morphology, and Exploratory Behavior.

PubMed

Katharesan, Viythia; Lewis, Martin David; Vink, Robert; Johnson, Ian Paul

2016-01-01

An overall increase in inflammatory cytokines with age in both the blood and the central nervous system (CNS) has been proposed to explain many aspects of ageing, including decreased motor function and neurodegeneration. This study tests the hypothesis that age-related increases in inflammatory cytokines in the blood and CNS lead to facial motor neuron degeneration. Groups of 3-5 female Sprague-Dawley rats aged 3, 12-18, and 24 months were used. Twelve cytokines interleukin (IL)-1α, IL-β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNFα), interferon-γ, and granulocyte macrophage-colony stimulating factor were measured in blood plasma and compared with those in the brainstem after first flushing blood from its vessels. The open-field test was used to measure exploratory behavior, and the morphology of the peripheral target muscle of facial motor neurons quantified. Total numbers of facial motor neurons were determined stereologically in separate groups of 3- and 24-month-old rats. Ageing rats showed a significant 30-42% decrease in blood plasma (peripheral) concentrations of IL-12p70 and TNFα and a significant 43-49% increase in brainstem (central) concentrations of IL-1α, IL-2, IL-4, IL-10, and TNFα. They also showed significant reductions in motor neuron number in the right but not left facial nucleus, reduced exploratory behavior, and increase in peripheral target muscle size. Marginal age-related facial motoneuronal loss occurs in the ageing rat and is characterized by complex changes in the inflammatory signature, rather than a general increase in inflammatory cytokines.

HIV Behavioral Research Online

PubMed Central

Parsons, Jeffrey T.; Tesoriero, James M.; Carballo-Dieguez, Alex; Hirshfield, Sabina; Remien, Robert H.

2006-01-01

Internet access has caused a global revolution in the way people of all ages and genders interact. Many have turned to the Internet to seek love, companionship, and sex, prompting researchers to move behavioral studies online. The sexual behavior of men who have sex with men (MSM) has been more closely studied than that of any other group online given the abundance of gay-oriented websites and concerns about increasing transmission of HIV and other sexually transmitted infections. Not only does the Internet provide a new medium for the conduct of behavioral research and for participant recruitment into an array of research studies, it has the as yet unrealized potential to reach huge numbers of MSM with innovative harm reduction and prevention messages tailored to individualized needs, interests, and risk behavior. Internet-based research on sexual behavior has many advantages in rapidity of recruitment of diverse samples which include individuals unreachable through conventional methods (i.e., non-gay identified and geographically and socially isolated MSM, etc.). Internet-based research also presents some new methodologic challenges in study design, participant recruitment, survey implementation, and interpretation of results. In addition, there are ethical issues unique to online research including difficulties in verifying informed consent, obstacles to surveying minors, and the ability to assure anonymity. This paper presents a review of Internet-based research on sexual behavior in MSM, a general discussion of the methodologic and ethical challenges of Internet-based research, and recommendations for future interdisciplinary research. PMID:16736356

HIV behavioral research online.

PubMed

Chiasson, Mary Ann; Parsons, Jeffrey T; Tesoriero, James M; Carballo-Dieguez, Alex; Hirshfield, Sabina; Remien, Robert H

2006-01-01

Internet access has caused a global revolution in the way people of all ages and genders interact. Many have turned to the Internet to seek love, companionship, and sex, prompting researchers to move behavioral studies online. The sexual behavior of men who have sex with men (MSM) has been more closely studied than that of any other group online given the abundance of gay-oriented websites and concerns about increasing transmission of HIV and other sexually transmitted infections. Not only does the Internet provide a new medium for the conduct of behavioral research and for participant recruitment into an array of research studies, it has the as yet unrealized potential to reach huge numbers of MSM with innovative harm reduction and prevention messages tailored to individualized needs, interests, and risk behavior. Internet-based research on sexual behavior has many advantages in rapidity of recruitment of diverse samples which include individuals unreachable through conventional methods (i.e., non-gay identified and geographically and socially isolated MSM, etc.). Internet-based research also presents some new methodologic challenges in study design, participant recruitment, survey implementation, and interpretation of results. In addition, there are ethical issues unique to online research including difficulties in verifying informed consent, obstacles to surveying minors, and the ability to assure anonymity. This paper presents a review of Internet-based research on sexual behavior in MSM, a general discussion of the methodologic and ethical challenges of Internet-based research, and recommendations for future interdisciplinary research.

Nonlinearities in Behavioral Macroeconomics.

PubMed

Gomes, Orlando

2017-07-01

This article undertakes a journey across the literature on behavioral macroeconomics, with attention concentrated on the nonlinearities that the behavioral approach typically suggests or implies. The emphasis is placed on thinking the macro economy as a living organism, composed of many interacting parts, each one having a will of its own, which is in sharp contrast with the mechanism of the orthodox view (well represented by the neoclassical or new Keynesian dynamic stochastic general equilibrium - DSGE - model). The paper advocates that a thorough understanding of individual behavior in collective contexts is the only possible avenue to further explore macroeconomic phenomena and the often observed 'anomalies' that the benchmark DSGE macro framework is unable to explain or justify. After a reflection on the role of behavioral traits as a fundamental component of a new way of thinking the economy, the article proceeds with a debate on some of the most relevant frameworks in the literature that somehow link macro behavior and nonlinearities; covered subjects include macro models with disequilibrium rules, agent-based models that highlight interaction and complexity, evolutionary switching frameworks, and inattention based decision problems. These subjects have, as a fundamental point in common, the use of behavioral elements to transform existing interpretations of the economic reality, making it more evident how irregular fluctuations emerge and unfold on the aggregate.

Physiology, behavior, and conservation.

PubMed

Cooke, Steven J; Blumstein, Daniel T; Buchholz, Richard; Caro, Tim; Fernández-Juricic, Esteban; Franklin, Craig E; Metcalfe, Julian; O'Connor, Constance M; St Clair, Colleen Cassady; Sutherland, William J; Wikelski, Martin

2014-01-01

Many animal populations are in decline as a result of human activity. Conservation practitioners are attempting to prevent further declines and loss of biodiversity as well as to facilitate recovery of endangered species, and they often rely on interdisciplinary approaches to generate conservation solutions. Two recent interfaces in conservation science involve animal behavior (i.e., conservation behavior) and physiology (i.e., conservation physiology). To date, these interfaces have been considered separate entities, but from both pragmatic and biological perspectives, there is merit in better integrating behavior and physiology to address applied conservation problems and to inform resource management. Although there are some institutional, conceptual, methodological, and communication-oriented challenges to integrating behavior and physiology to inform conservation actions, most of these barriers can be overcome. Through outlining several successful examples that integrate these disciplines, we conclude that physiology and behavior can together generate meaningful data to support animal conservation and management actions. Tangentially, applied conservation and management problems can, in turn, also help advance and reinvigorate the fundamental disciplines of animal physiology and behavior by providing advanced natural experiments that challenge traditional frameworks.

Behavior and Performance Project

NASA Technical Reports Server (NTRS)

Washburn, David A.; Rumbaugh, Duane M.; Shlyk, Galina; Vassilieva, Oxana; Richardson, W. Kirk

1998-01-01

Behavior is an overt manifestation of underlying biology. As such, alterations in biological systems that result from spaceflight would be expected to evidence themselves in subtle or even pronounced changes in the behavior of that organism. These alterations in visible behavior may then indicate or even be diagnostic of alterations in the physical well-being of humans and other animals as they adapt to space environments or readapt to Earth--alterations that might not otherwise be detected without relatively invasive and frequently expensive procedures. Moreover, behavior and performance constitute the central standard for evaluating the mission success of spaceflight ventures. The success or failure of any excursion into space is primarily indexed by the ability of astronauts and cosmonauts to perform the tasks and experiments of any particular mission, to land a re-entry vehicle after extended exposure to microgravity (as with the space shuttle), or to make time-critical and life-saving repairs or other decisions while in orbit (as with the recent Mir events). Thus, understanding the effects spaceflight on behavior and performance is inherently important, in addition to those insights that behavior can provide about the physiological consequences of space adaptation.

Behavior Modification in the Classroom

ERIC Educational Resources Information Center

Whitman, Mryon; Whitman, Joan

1971-01-01

This article presents the theoretical rationale for behavior modification, principally through its comparison with traditional psychotherapies, and suggests some behavior modification techniques for the classroom management of maladaptive behavior. (Author)

Facilitator control as automatic behavior: A verbal behavior analysis

PubMed Central

Hall, Genae A.

1993-01-01

Several studies of facilitated communication have demonstrated that the facilitators were controlling and directing the typing, although they appeared to be unaware of doing so. Such results shift the focus of analysis to the facilitator's behavior and raise questions regarding the controlling variables for that behavior. This paper analyzes facilitator behavior as an instance of automatic verbal behavior, from the perspective of Skinner's (1957) book Verbal Behavior. Verbal behavior is automatic when the speaker or writer is not stimulated by the behavior at the time of emission, the behavior is not edited, the products of behavior differ from what the person would produce normally, and the behavior is attributed to an outside source. All of these characteristics appear to be present in facilitator behavior. Other variables seem to account for the thematic content of the typed messages. These variables also are discussed. PMID:22477083

Human Rights and Behavior Modification

ERIC Educational Resources Information Center

Roos, Philip

1974-01-01

Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

Behavioral Indicators and Behaviors Related to Sexting among Undergraduate Students

ERIC Educational Resources Information Center

Hudson, Heather K.; Fetro, Joyce V.; Ogletree, Roberta

2014-01-01

Background: Empirical studies on sexting are limited, and many sexting studies only assessed sexting behaviors. Few studies have assessed attitudes, subjective norms, or behavioral intentions related to sexting. Purpose: The purpose of this study was to assess attitudes, subjective norms, behavioral intentions, and behaviors related to sexting…

Surveying Professionals' Views of Positive Behavior Support and Behavior Analysis

ERIC Educational Resources Information Center

Filter, Kevin J.; Tincani, Matt; Fung, Daniel

2009-01-01

Positive behavior support (PBS) is an empirically driven approach to improve quality of life influenced by the science of behavior analysis. Recent discussions have evolved around PBS, behavior analysis, and their relationship within education and human services fields. To date, few data have been offered to guide behaviorally oriented…

Epilepsy, cognition and behavior.

PubMed

Gulati, Sheffali; Yoganathan, Sangeetha; Chakrabarty, Biswaroop

2014-10-01

Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have intellectual disability and behavioral co-morbidities to the tune of up to 25 and 75% respectively. Various factors like underlying etiology, socioeconomic environment at home, age at onset, seizure semiology, seizure descriptors like duration, severity and frequency, therapy related adverse effects secondary to antiepileptic drugs and epilepsy surgery have been implicated for the causation of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has emerged as a specific entity. This may manifest as a transient behavioral or cognitive change, insidous onset subacute to chronic encephalopathy or more catastrophic in the form of nonconvulsive status epilepticus. Cognitive impairment seen in epileptic children include difficulties in learning, memory, problem solving as well as concept formation. Anxiety, depression and attention deficit hyperkinetic disorders are the most common psychiatric co-morbidities seen. Investigating a child with epilepsy for cognitive and behavioral impairment is difficult as these tests would require cooperation from the patient's side to a significant extent. A rational approach towards treatment would be judicious selection of antiepileptic drugs, treatment of underlying cause, appropriate management of behavioral co-morbidities including psychopharmacotherapy and a trial of immunotherapy (particularly in cognitive epilepsies), wherever appropriate.

Behavior medicine specialist.

PubMed

Tuso, Phillip

2014-01-01

Total Health is a vision for the future and a strategy to prevent preventable disease, save lives, and make health care more affordable. Total Health means health of mind (behavior health) and health of body (physical health). To achieve Total Health we need healthy people in healthy communities. A behavior medicine specialist is a psychologist who works in the medical home with the primary care physician instead of in the Mental Health Department with a psychiatrist. The key to achieving Total Health will be to transform our current health care system from a focus on treating disease to a focus on preventing disease. This transformation will require complex behavior change interventions and services not usually provided in the medical home. The behavior medicine specialist will bring the knowledge and experience used to treat mental illness into the medical home to help the primary care physician improve the care of all patients in the medical home. The behavior medicine specialist will help improve outcomes in synergy with the primary care physician by universal screening of high-risk diseases, stepped care protocols, and efficient use of all resources available to care for patients in the medical home (health education classes, wellness coaches, and online social networking lifestyle management programs). These interventions should increase patient satisfaction, increase access to specialty care (psychiatry), and help us achieve Total Health.

Behavioral and Pharmacogenetics of Aggressive Behavior

PubMed Central

Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

2013-01-01

Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or

Feedback and efficient behavior

PubMed Central

2017-01-01

Feedback is an effective tool for promoting efficient behavior: it enhances individuals’ awareness of choice consequences in complex settings. Our study aims to isolate the mechanisms underlying the effects of feedback on achieving efficient behavior in a controlled environment. We design a laboratory experiment in which individuals are not aware of the consequences of different alternatives and, thus, cannot easily identify the efficient ones. We introduce feedback as a mechanism to enhance the awareness of consequences and to stimulate exploration and search for efficient alternatives. We assess the efficacy of three different types of intervention: provision of social information, manipulation of the frequency, and framing of feedback. We find that feedback is most effective when it is framed in terms of losses, that it reduces efficiency when it includes information about inefficient peers’ behavior, and that a lower frequency of feedback does not disrupt efficiency. By quantifying the effect of different types of feedback, our study suggests useful insights for policymakers. PMID:28430787

Adventure Behavior Seeking Scale

PubMed Central

Próchniak, Piotr

2017-01-01

This article presents a new tool—the Adventure Behavior Seeking Scale (ABSS). The Adventure Behavior Seeking Scale was developed to assess individuals’ highly stimulating behaviors in natural environments. An exploratory factor analysis was conducted with 466 participants and resulted in one factor. The internal consistency was 0.80. A confirmatory factor analysis was performed using another sample of 406 participants, and results verified the one-factor structure. The findings indicate that people with a lot of experience in outdoor adventure have a higher score on the ABSS scale than control groups without such experience. The results also suggest that the 8-item ABSS scores were highly related to sensation seeking. The author discusses findings in regard to the ABSS as an instrument to measure outdoor adventure. However, further studies need to be carried out in other sample groups to further validate the scale. PMID:28555018

Drugs and sexual behavior.

PubMed

Bruno, Antonio; Scimeca, Giuseppe; Marino, Antonio G; Mento, Carmela; Micò, Umberto; Romeo, Vincenzo M; Pandolfo, Gianluca; Zoccali, Rocco; Muscatello, Maria R A

2012-01-01

This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed.

Prosocial behavior: multilevel perspectives.

PubMed

Penner, Louis A; Dovidio, John F; Piliavin, Jane A; Schroeder, David A

2005-01-01

Current research on prosocial behavior covers a broad and diverse range of phenomena. We argue that this large research literature can be best organized and understood from a multilevel perspective. We identify three levels of analysis of prosocial behavior: (a) the "meso" level--the study of helper-recipient dyads in the context of a specific situation; (b) the micro level--the study of the origins of prosocial tendencies and the sources of variation in these tendencies; and (c) the macro level--the study of prosocial actions that occur within the context of groups and large organizations. We present research at each level and discuss similarities and differences across levels. Finally, we consider ways in which theory and research at these three levels of analysis might be combined in future intra- and interdisciplinary research on prosocial behavior.

Prevention of suicidal behavior

PubMed Central

Hegerl, Ulrich

2016-01-01

More than 800 000 people die every year from suicide, and about 20 times more attempt suicide. In most countries, suicide risk is highest in older males, and risk of attempted suicide is highest in younger females. The higher lethal level of suicidal acts in males is explained by the preference for more lethal methods, as well as other factors. In the vast majority of cases, suicidal behavior occurs in the context of psychiatric disorders, depression being the most important one. Improving the treatment of depression, restricting access to lethal means, and avoiding the Werther effect (imitation suicide) are central aspects of suicide prevention programs. In several European regions, the four-level intervention concept of the European Alliance Against Depression (www.EAAD.net), simultaneously targeting depression and suicidal behavior, has been found to have preventive effects on suicidal behavior. It has already been implemented in more than 100 regions in Europe. PMID:27489458

Behavior treatment: general considerations.

PubMed

Gardner, William I

2005-01-01

The principal goal of behavior treatment for retarded clients is that of modifying behavior as it occurs in a given environment in such a manner that it becomes more appropriate to that environment. The therapeutic or change agents can involve a variety of persons other than the counselor, teacher, and client--this may include parents, peers, work supervisors and others who can provide supportive influences. Education and rehabilitation programs should be tailored to the occupational and social environment of the retarded client and designed to teach those behavior patterns that are relevant to that environment. Additionally, the work tasks for which retarded clients are trained should be highly structured and routine. Excessive demand for adaptability or decision making is a major cause of training failure for retarded clients.

Hatching behavior in turtles.

PubMed

Spencer, Ricky-John; Janzen, Fredric J

2011-07-01

Incubation temperature plays a prominent role in shaping the phenotypes and fitness of embryos, including affecting developmental rates. In many taxa, including turtles, eggs are deposited in layers such that thermal gradients alter developmental rates within a nest. Despite this thermal effect, a nascent body of experimental work on environmentally cued hatching in turtles has revealed unexpected synchronicity in hatching behavior. This review discusses environmental cues for hatching, physiological mechanisms behind synchronous hatching, proximate and ultimate causes for this behavior, and future directions for research. Four freshwater turtle species have been investigated experimentally, with hatching in each species elicited by different environmental cues and responding via various physiological mechanisms. Hatching of groups of eggs in turtles apparently involves some level of embryo-embryo communication and thus is not a purely passive activity. Although turtles are not icons of complex social behavior, life-history theory predicts that the group environment of the nest can drive the evolution of environmentally cued hatching.

Rationality and social behavior.

PubMed

Tullberg, Jan

2003-10-21

This article penetrates the relationship between social behavior and rationality. A critical analysis is made of efforts to classify some behaviors as altruistic, as they simultaneously meet criteria of rationality by not truly being self-destructive. Newcomb's paradox is one attempt to create a hybrid behavior that is both irrational and still meets some criterion of rationality. Such dubious rationality is often seen as a source of altruistic behavior. Group selection is a controversial topic. Sober and Wilson (Unto Others--The Evolution and Psychology of Unselfish Behavior, Harvard University Press, Cambridge, MA, 1998) suggest that a very wide concept of group selection might be used to explain altruism. This concept also includes kin selection and reciprocity, which blurs its focus. The latter mechanisms hardly need further arguments to prove their existence. This article suggests that it is group selection in a strict sense that should be investigated to limit semantic neologism and confusion. In evaluation, the effort to muster a mechanism for altruism out of group selection has not been successful. However, this is not the end to group selection, but rather a good reason to investigate more promising possibilities. There is little reason to burden group selection with the instability of altruism caused by altruistic members of a group having lower fitness than egoistic members. Group selection is much more likely to develop in combination with group egoism. A common project is supported by incitement against free riding, where conformist members joined in solidarity achieve a higher fitness than members pursuing more individualistic options. Group egoism is in no conflict with rationality, and the effects of group selection will be supported rather than threatened by individual selection. Empirical evidence indicates a high level of traits such as conformism and out-group antagonism in line with group egoism. These traits are also likely candidates for

Is extraordinary prosocial behavior more valuable than ordinary prosocial behavior?

PubMed

Futamura, Ikumi

2018-01-01

This study examined how people evaluate ordinary and extraordinary prosocial behaviors, especially their predictions of the likelihood of future prosocial behaviors of ordinary and extraordinary prosocial actors (Study 1). Further, it examined the individual effects of ordinary and extraordinary prosocial behaviors of an actor on the evaluation of his/her trait by considering the cases where the actor engages in and does not engage in the other behavior (Study 2). Study 1 revealed that the likelihood of future prosocial behaviors of ordinary and extraordinary prosocial actors was perceived asymmetrically. Specifically, while the likelihood of ordinary prosocial actors to engage in ordinary prosocial behaviors was perceived as high, the same perception was not observed for extraordinary prosocial behaviors. On the other hand, extraordinary prosocial actors were perceived as highly likely to engage in both ordinary and extraordinary prosocial behaviors. Study 2 revealed that the evaluation of actors who engaged in extraordinary prosocial behaviors but not ordinary prosocial behaviors did not exceed the evaluation of actors who engaged in ordinary prosocial behaviors but not extraordinary prosocial behaviors. Additionally, the effect of extraordinary prosocial behaviors was more when the actor also engaged in ordinary prosocial behaviors. These results suggest that extraordinary prosocial actors are evaluated highly when they also engage in ordinary prosocial behaviors.

Is extraordinary prosocial behavior more valuable than ordinary prosocial behavior?

PubMed Central

2018-01-01

This study examined how people evaluate ordinary and extraordinary prosocial behaviors, especially their predictions of the likelihood of future prosocial behaviors of ordinary and extraordinary prosocial actors (Study 1). Further, it examined the individual effects of ordinary and extraordinary prosocial behaviors of an actor on the evaluation of his/her trait by considering the cases where the actor engages in and does not engage in the other behavior (Study 2). Study 1 revealed that the likelihood of future prosocial behaviors of ordinary and extraordinary prosocial actors was perceived asymmetrically. Specifically, while the likelihood of ordinary prosocial actors to engage in ordinary prosocial behaviors was perceived as high, the same perception was not observed for extraordinary prosocial behaviors. On the other hand, extraordinary prosocial actors were perceived as highly likely to engage in both ordinary and extraordinary prosocial behaviors. Study 2 revealed that the evaluation of actors who engaged in extraordinary prosocial behaviors but not ordinary prosocial behaviors did not exceed the evaluation of actors who engaged in ordinary prosocial behaviors but not extraordinary prosocial behaviors. Additionally, the effect of extraordinary prosocial behaviors was more when the actor also engaged in ordinary prosocial behaviors. These results suggest that extraordinary prosocial actors are evaluated highly when they also engage in ordinary prosocial behaviors. PMID:29684088

Behavioral Nutraceuticals and Diets.

PubMed

Orlando, Jillian M

2018-05-01

Behavioral problems of companion animals are becoming more widely recognized. As a result, there are a growing number of behavioral nutraceuticals and diets on the market. These products may be useful for the treatment of mild conditions, for clients who are hesitant to give their pet a psychopharmacologic agent, or sometimes in conjunction with psychopharmacologic agents. Veterinarians should critically review the research associated with nutraceuticals and diets, and have an understanding of the functional ingredients and their mechanisms of action before prescribing treatment. This article provides an overview of nutraceuticals, their mechanisms of action, and relevant research regarding their use. Copyright © 2018 Elsevier Inc. All rights reserved.

Zen and Behavior Analysis

PubMed Central

Bass, Roger

2010-01-01

Zen's challenge for behavior analysis is to explain a repertoire that renders analysis itself meaningless—a result following not from scientific or philosophical arguments but rather from a unique verbal history generated by Zen's methods. Untying Zen's verbal knots suggests how meditation's and koans' effects on verbal behavior contribute to Enlightenment and Samādhi. The concept of stimulus singularity is introduced to account for why, within Zen's frame of reference, its methods can be studied but its primary outcomes (e.g., Samādhi and Satori) cannot be described in any conventional sense. PMID:22479128

Suicidal Behavior among Latino Youth.

ERIC Educational Resources Information Center

Canino, Glorisa; Roberts, Robert E.

2001-01-01

Reviews the scientific literature related to suicidal behavior among Latino youth. Discusses the conceptualizations of culture, and how culture may influence behavior and psychopathology, in particular, suicidal behavior. Reviews the literature that discusses rates of suicidal behavior, risk, and protective factors associated with this behavior…

Behavioral Tolerance to Anticholinergic Agents

DTIC Science & Technology

1986-11-20

Medicine , 47, 137-141. 7. Kurtz, P.J. (1977) Behavioral and biochemical effects of the carbamate insecticide, mobam. Pharmacology Biochemistry & Behavior...tolerance to marihuana in rats. Pharmacology Biochemistry and Behavior, 1, 73-76. 43 40. Olson, J. and Carder, B. (1974) Behavioral tolerance to... marihuana as a function of amount of prior training. Pharmacology Biochemistry and Behavior, 2, 243-247. 41. Sidman, M. (1960) Tactics of Scientific

Promoting Adolescents' Prosocial Behavior

ERIC Educational Resources Information Center

Kidron, Yael; Fleischman, Steve

2006-01-01

Saying a kind word to a classmate, acknowledging other students' feelings, sharing books and advice, defending a victim of bullying--these are just a few of the prosocial behaviors that can enhance students' social and academic lives at school. Because children do not develop social values in a vacuum, educators, policymakers, and researchers are…

Prosocial behavior and gender

PubMed Central

Espinosa, María Paz; Kovářík, Jaromír

2015-01-01

This study revisits different experimental data sets that explore social behavior in economic games and uncovers that many treatment effects may be gender-specific. In general, men and women do not differ in “neutral” baselines. However, we find that social framing tends to reinforce prosocial behavior in women but not men, whereas encouraging reflection decreases the prosociality of males but not females. The treatment effects are sometimes statistically different across genders and sometimes not but never go in the opposite direction. These findings suggest that (i) the social behavior of both sexes is malleable but each gender responds to different aspects of the social context; and (ii) gender differences observed in some studies might be the result of particular features of the experimental design. Our results contribute to the literature on prosocial behavior and may improve our understanding of the origins of human prosociality. We discuss the possible link between the observed differential treatment effects across genders and the differing male and female brain network connectivity, documented in recent neural studies. PMID:25926783

Shaping Adolescent Gambling Behavior.

ERIC Educational Resources Information Center

Arcuri, Alan F.; And Others

1985-01-01

Surveyed the incidence of casino gambling by adolescents. Results indicated that 64 percent of the students at one Atlantic City high school had gambled at the casinos. The dangers of shaping compulsive gambling behavior through societal acceptance of legalized gambling are discussed. (Author/BL)

Studies of Supervisory Behavior.

ERIC Educational Resources Information Center

Sistrunk, Walter E.

A series of supervisory behavior studies that began at Mississippi State University in 1980 are summarized. The studies were instigated because of interest in effective supervision and dissatisfaction with an indepth literature search of supervision literature. The theories disclosed were fragmentary, contradictory, and impractical for use by…

Brain Chemistry and Behavior.

ERIC Educational Resources Information Center

Spaziano, Vincent T.; Gibbons, Judith L.

1986-01-01

Describes an interdisciplinary course providing basic background in behavior, pharmacology, neuroanatomy, neurotransmitters, drugs, and specific brain disorders. Provides rationale, goals, and operational details. Discusses a research project as a tool to improve critical evaluation of science reporting and writing skills. (JM)

Measuring Neurotic Behavior.

ERIC Educational Resources Information Center

Blai, Boris, Jr.

An exploratory study concerned with the measurement of perseveration, or persistence, as a personality variable was based on the work of G.V. Hamilton, an early investigator in the field. Persistently maladaptive behavior was hypothesized to be a chief characteristic of neurosis. An experimental problem-solving situation was designed to…

Effective Principal Behaviors.

ERIC Educational Resources Information Center

Research for Better Schools, Inc., Philadelphia, PA.

This paper summarizes research findings related to the performance behaviors of effective school principals. It identifies eight characteristics of effective schools: (1) schoolwide measurement and recognition of academic success; (2) high emphasis on curriculum articulation; (3) support for instructional tasks; (4) high expectations and clear…

Diabetes and Behavior.

ERIC Educational Resources Information Center

Surwit, Richard S.; And Others

1983-01-01

Suggests that the problem of effective care of diabetes mellitus presents an opportunity for the emerging field of health psychology. Discusses behavioral interventions that aid in treatment of this disease by reducing its energy mobilizing effects on the nervous system. (Author/AOS)

Television and Human Behavior.

ERIC Educational Resources Information Center

Comstock, George; And Others

To compile a comprehensive review of English language scientific literature regarding the effects of television on human behavior, the authors of this book evaluated more than 2,500 books, articles, reports, and other documents. Rather than taking a traditional approach, the authors followed a new model for the retrieval and synthesis of…

Uncertainty in Wildfire Behavior

NASA Astrophysics Data System (ADS)

Finney, M.; Cohen, J. D.

2013-12-01

The challenge of predicting or modeling fire behavior is well recognized by scientists and managers who attempt predictions of fire spread rate or growth. At the scale of the spreading fire, the uncertainty in winds, moisture, fuel structure, and fire location make accurate predictions difficult, and the non-linear response of fire spread to these conditions means that average behavior is poorly represented by average environmental parameters. Even more difficult are estimations of threshold behaviors (e.g. spread/no-spread, crown fire initiation, ember generation and spotting) because the fire responds as a step-function to small changes in one or more environmental variables, translating to dynamical feedbacks and unpredictability. Recent research shows that ignition of fuel particles, itself a threshold phenomenon, depends on flame contact which is absolutely not steady or uniform. Recent studies of flame structure in both spreading and stationary fires reveals that much of the non-steadiness of the flames as they contact fuel particles results from buoyant instabilities that produce quasi-periodic flame structures. With fuel particle ignition produced by time-varying heating and short-range flame contact, future improvements in fire behavior modeling will likely require statistical approaches to deal with the uncertainty at all scales, including the level of heat transfer, the fuel arrangement, and weather.

Compulsive Sexual Behavior

MedlinePlus

... to hurt yourself or someone else, you report sexual abuse of a child, or you report abuse or neglect of someone in a vulnerable population. Seek treatment right away Seek immediate ... uncontrolled sexual behavior You have other problems with impulse control, ...

Behavioral management of obesity

USDA-ARS?s Scientific Manuscript database

The behavioral management of obesity is an approach designed to provide individuals with a set of skills that promote a healthier weight. A number of strategies are used to assist individuals in making gradual changes that can realistically be incorporated into their lives. Evidence is promising f...

Girls' Aggressive Behavior

ERIC Educational Resources Information Center

Owens, Larry; Shute, Rosalyn; Slee, Phillip

2004-01-01

In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

Japanese Patterns of Behavior.

ERIC Educational Resources Information Center

Lebra, Takie Sugiyama

This book attempts to shed light on the seemingly contradictory aspects of Japanese behavior. Separate chapters, grounded in interaction-oriented social scientific theory, focus on the themes of social relativism, belongingness, empathy, dependency, occupying the proper place, reciprocity, situational interaction, early socialization, selfhood,…

Behavioral Task Analysis

DTIC Science & Technology

2010-01-01

and related tech- nologies . Washington, DC: National Academies Press. Neisser , U . (1967) . Cognitive psychology. New York: Appleton-Century-Crofts...behavior (see Neisser [1967] for a review of the early stages of information processing). The result is a characterization of human tasks as involving

Managing Surface Behaviors.

ERIC Educational Resources Information Center

Marable, Michele A.; Raimondi, Sharon L.

1995-01-01

Nonverbal and verbal techniques that teachers can use to manage surface behaviors are suggested, including planned ignoring, eye contact, facial expression, body posture, close proximity, touch control, limitation of space, redirection to another activity, ventilation, distraction, understanding and reassurance, modeling, humor, one-to-one…

Behavioral Screening for Toxicology

EPA Science Inventory

Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols use...

Food Affects Human Behavior.

ERIC Educational Resources Information Center

Kolata, Gina

1982-01-01

A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

Neuroticism and proxemic behavior.

PubMed

De Julio, S; Duffy, K

1977-08-01

The relationship between proxemic behavior and neuroticism was examined. 50 male and 43 female subjects individually self-selected seats in a classroom where they were administered the Eysenck Personality Inventory by one of four experimenters (two male, two female). A significant relationship was found between proxemic distance and both neuroticism and experimenter's sex.

Variations in Sexual Behavior.

ERIC Educational Resources Information Center

Juhasz, Anne McCreary

1983-01-01

Questions are raised about the difficulty of defining normal and atypical sexual behavior. Variations from normalcy that students, parents, and educators are most likely to encounter are discussed. The importance of dealing with variations in ways that are best for the individual and the group is emphasized. (PP)

Exercise and Compulsive Behavior.

ERIC Educational Resources Information Center

Polivy, Janet; Clendenen, Vanessa

Although reports on the positive effects of fitness and exercise predominate in the exercise literature, some researchers describe frequent exercise as compulsive or addictive behavior. This paper addresses these "negative addictions" of exercise. As early as 1970, researchers recognized the addictive qualities of exercise. Short-term…

Neurobiology of aggressive behavior.

PubMed

Delgado, J M

1976-10-30

Causality, neurological mechanisms, and behavioral manifestations may be heterogeneous in different forms of aggressive behavior, but some elements are shared by all forms of violence, including the necessity of sensory inputs, the coding and decoding of information according to acquired frames of reference, and the activation of pre-established patterns of response. Understanding and prevention of violence requires a simultaneous study of its social, cultural, and economic aspects, at parity with an investigation of its neurological mechanisms. Part of the latter information may be obtained through animal experimentation, preferably in non-human primates. Feline predatory behavior has no equivalent in man, and therefore its hypothalamic representation probably does not exist in the human brain. Codes of information, frames of reference for sensory perception, axis to evaluate threats, and formulas for aggressive performance are not established genetically but must be learned individually. We are born with the capacity to learn aggressive behavior, but not with established patterns of violence. Mechanisms for fighting which are acquired by individual experience may be triggered in a similar way by sensory cues, volition, and by electrical stimulation of specific cerebral areas. In monkeys, aggressive responses may be modified by changing the hierarchical position of the stimulated animal, indicating the physiological quality of the neurological mechanisms electrically activated.

Mathematics as verbal behavior.

PubMed

Marr, M Jackson

2015-04-01

"Behavior which is effective only through the mediation of other persons has so many distinguishing dynamic and topographical properties that a special treatment is justified and indeed demanded" (Skinner, 1957, p. 2). Skinner's demand for a special treatment of verbal behavior can be extended within that field to domains such as music, poetry, drama, and the topic of this paper: mathematics. For centuries, mathematics has been of special concern to philosophers who have continually argued to the present day about what some deem its "special nature." Two interrelated principal questions have been: (1) Are the subjects of mathematical interest pre-existing in some transcendental realm and thus are "discovered" as one might discover a new planet; and (2) Why is mathematics so effective in the practices of science and engineering even though originally such mathematics was "pure" with applications neither contemplated or even desired? I argue that considering the actual practice of mathematics in its history and in the context of acquired verbal behavior one can address at least some of its apparent mysteries. To this end, I discuss some of the structural and functional features of mathematics including verbal operants, rule-and contingency-modulated behavior, relational frames, the shaping of abstraction, and the development of intuition. How is it possible to understand Nature by properly talking about it? Essentially, it is because nature taught us how to talk. Copyright © 2015 Elsevier B.V. All rights reserved.

Applied Behavior Analysis

ERIC Educational Resources Information Center

Szapacs, Cindy

2006-01-01

Teaching strategies that work for typically developing children often do not work for those diagnosed with an autism spectrum disorder. However, teaching strategies that work for children with autism do work for typically developing children. In this article, the author explains how the principles and concepts of Applied Behavior Analysis can be…

Cosmetic Behavior Therapy.

ERIC Educational Resources Information Center

Jones, W. Paul

1980-01-01

Discusses the theoretical and practical applications of cosmetic behavior therapy in a private practice. Enhancement of physical appearance will frequently result in an enhancement of self-concept, and the client's attainment of physical attractiveness contributes to the probability of success in current culture. (Author/JAC)

An opinion-driven behavioral dynamics model for addictive behaviors

NASA Astrophysics Data System (ADS)

Moore, Thomas W.; Finley, Patrick D.; Apelberg, Benjamin J.; Ambrose, Bridget K.; Brodsky, Nancy S.; Brown, Theresa J.; Husten, Corinne; Glass, Robert J.

2015-04-01

We present a model of behavioral dynamics that combines a social network-based opinion dynamics model with behavioral mapping. The behavioral component is discrete and history-dependent to represent situations in which an individual's behavior is initially driven by opinion and later constrained by physiological or psychological conditions that serve to maintain the behavior. Individuals are modeled as nodes in a social network connected by directed edges. Parameter sweeps illustrate model behavior and the effects of individual parameters and parameter interactions on model results. Mapping a continuous opinion variable into a discrete behavioral space induces clustering on directed networks. Clusters provide targets of opportunity for influencing the network state; however, the smaller the network the greater the stochasticity and potential variability in outcomes. This has implications both for behaviors that are influenced by close relationships verses those influenced by societal norms and for the effectiveness of strategies for influencing those behaviors.

Increasing the on-Task Homework Behavior of Youth with Behavior Disorders Using Functional Behavioral Assessment

ERIC Educational Resources Information Center

Hawkins, Renee O.; Axelrod, Michael I.

2008-01-01

Research has shown a positive correlation between time spent on homework and learning. However, students often engage in off-task behaviors to escape the demands of homework. Youth with emotional or behavioral disorders (EBD) are especially likely to engage in off-task behaviors. Effective interventions to increase on-task behavior during homework…

Maternal Antisocial Behavior, Parenting Practices, and Behavior Problems in Boys at Risk for Antisocial Behavior

ERIC Educational Resources Information Center

Ehrensaft, Miriam K.; Wasserman, Gail A.; Verdelli, Lena; Greenwald, Steven; Miller, Laurie S.; Davies, Mark

2003-01-01

We investigated the independent contributions of maternal history of antisocial behavior and parenting practices to the worsening course of sons' behavior problems in a sample of young urban boys at risk for antisocial behavior. Mothers reported on boys' behavior problems at baseline and one year later, as well as on their own history of…

Behaviorism, Private Events, and the Molar View of Behavior

PubMed Central

Baum, William M

2011-01-01

Viewing the science of behavior (behavior analysis) to be a natural science, radical behaviorism rejects any form of dualism, including subjective–objective or inner–outer dualism. Yet radical behaviorists often claim that treating private events as covert behavior and internal stimuli is necessary and important to behavior analysis. To the contrary, this paper argues that, compared with the rejection of dualism, private events constitute a trivial idea and are irrelevant to accounts of behavior. Viewed in the framework of evolutionary theory or for any practical purpose, behavior is commerce with the environment. By its very nature, behavior is extended in time. The temptation to posit private events arises when an activity is viewed in too small a time frame, obscuring what the activity does. When activities are viewed in an appropriately extended time frame, private events become irrelevant to the account. This insight provides the answer to many philosophical questions about thinking, sensing, and feeling. Confusion about private events arises in large part from failure to appreciate fully the radical implications of replacing mentalistic ideas about language with the concept of verbal behavior. Like other operant behavior, verbal behavior involves no agent and no hidden causes; like all natural events, it is caused by other natural events. In a science of behavior grounded in evolutionary theory, the same set of principles applies to verbal and nonverbal behavior and to human and nonhuman organisms. PMID:22532740

The brain stem saccadic burst generator encodes gaze in three-dimensional space.

PubMed

Van Horn, Marion R; Sylvestre, Pierre A; Cullen, Kathleen E

2008-05-01

When we look between objects located at different depths the horizontal movement of each eye is different from that of the other, yet temporally synchronized. Traditionally, a vergence-specific neuronal subsystem, independent from other oculomotor subsystems, has been thought to generate all eye movements in depth. However, recent studies have challenged this view by unmasking interactions between vergence and saccadic eye movements during disconjugate saccades. Here, we combined experimental and modeling approaches to address whether the premotor command to generate disconjugate saccades originates exclusively in "vergence centers." We found that the brain stem burst generator, which is commonly assumed to drive only the conjugate component of eye movements, carries substantial vergence-related information during disconjugate saccades. Notably, facilitated vergence velocities during disconjugate saccades were synchronized with the burst onset of excitatory and inhibitory brain stem saccadic burst neurons (SBNs). Furthermore, the time-varying discharge properties of the majority of SBNs (>70%) preferentially encoded the dynamics of an individual eye during disconjugate saccades. When these experimental results were implemented into a computer-based simulation, to further evaluate the contribution of the saccadic burst generator in generating disconjugate saccades, we found that it carries all the vergence drive that is necessary to shape the activity of the abducens motoneurons to which it projects. Taken together, our results provide evidence that the premotor commands from the brain stem saccadic circuitry, to the target motoneurons, are sufficient to ensure the accurate control shifts of gaze in three dimensions.

Lateralized hyperkinetic motor behavior.

PubMed

Krishnaiah, Balaji; Acharya, Jayant; Ahmed, Aiesha

2018-01-01

Seizures are followed by a post-ictal period, which is characterized by usual slowing of brain activity. This case report describes a 68-year old woman who presented with right-sided rhythmic, non-voluntary, semi-purposeful motor behavior that started 2 days after an episode of generalized seizure. Her initial electroencephalogram (EEG) showed beta activity with no evidence of epileptiform discharges. Computed tomography scan showed hypodensity in the left parieto-occipital region. Magnetic resonance imaging (MRI) showed restricted diffusion/fluid-attenuated inversion recovery hyperintensities in the left precentral and post-central gyrus. Unilateral compulsive motor behavior during the post-ictal state should be considered, and not confused with partial status epilepticus to avoid unnecessary treatment. Abnormal magnetic resonance imaging (MRI) findings, which are reversible, can help with the diagnostic and therapeutic approach.

Media and risky behaviors.

PubMed

Escobar-Chaves, Soledad Liliana; Anderson, Craig A

2008-01-01

Liliana Escobar-Chaves and Craig Anderson investigate two important trends among American youth and examine the extent to which the two trends might be related. First, the authors note that U.S. youth are spending increasing amounts of time using electronic media, with the average American youngster now spending one-third of each day with some form of electronic media. Second, the authors demonstrate that American adolescents are engaging in a number of unhealthful behaviors that impose huge societal costs. Escobar-Chaves and Anderson detail the extent of five critical types of adolescent health risk behaviors identified by the Centers for Disease Control and Prevention-obesity, smoking, drinking, sexual risk taking, and violence. Obesity, the authors note, has become an epidemic among America's young people. Cigarette smoking among adolescents is one of the ten leading health indicators of greatest government concern. Alcohol abuse and alcohol dependence are widespread problems among the nation's youth and are the source of the three leading causes of death among youth. More than 20 percent of American high school students have sexual intercourse for the first time before they reach the age of fourteen. And twelve- to twenty-year-olds perpetrated 28 percent of the single-offender and 41 percent of multiple-offender violent crimes in the United States in 2005. Escobar-Chaves and Anderson present and evaluate research findings on the influence of electronic media on these five risk behaviors among adolescents. Researchers, they say, have found modest evidence that media consumption contributes to the problem of obesity, modest to strong evidence that it contributes to drinking and smoking, and strong evidence that it contributes to violence. Research has been insufficient to find links between heavy media exposure and early sexual initiation. The authors note the need for more large-scale longitudinal studies that specifically examine the cumulative effects of

Consumer behavior: a quadrennium.

PubMed

Jacoby, J; Johar, G V; Morrin, M

1998-01-01

Consumer behavior continued to attract additional researchers and publication outlets from 1993 through 1996. Both general interest and domain-specific scholarly contributions are discussed, along with limitations and suggested areas for future research. A concluding section observes that the integrity of consumer research is unnecessarily compromised by the failure of the major scholarly association in the field to develop and adopt a code of researcher ethics.

Behavioral Genetic Analyses of Prosocial Behavior in Adolescents

ERIC Educational Resources Information Center

Gregory, Alice M.; Light-Hausermann, Jade H.; Rijsdijk, Fruhling; Eley, Thalia C.

2009-01-01

Prosocial behavior is an important aspect of normal social and psychological development. Adult and child twin studies typically estimate the heritability of prosocial behavior to be between 30 and 50%, although relatively little is known about genetic and environmental influences upon prosocial behavior in adolescence. We therefore examined…

Predictors of Health Behavior from a Behavior-Analytic Orientation.

ERIC Educational Resources Information Center

Birkimer, John C.; And Others

1996-01-01

Discovers a high correlation between positive emotional states, supportive self talk, and specific healthy behaviors in college students. The correlated health behaviors were vigorous exercise, mild exercise, seat belts, and avoidance of alcohol and junk food. Considers the impact of negative self talk on the avoidance of negative behavior. (MJP)

The Impact of Skinner's "Verbal Behavior" on Organizational Behavior Management

ERIC Educational Resources Information Center

Fox, Eric J.; VanStelle, Sarah E.

2010-01-01

In the book "Verbal Behavior," Skinner provided a comprehensive, behavioral account of language. While the impact of Skinner's analysis on empirical research has been examined broadly, this review of the literature focused on studies relevant to organizational behavior management (OBM). Both empirical and nonempirical journal articles in OBM were…

Early Adolescent Risk Behavior Outcomes of Childhood Externalizing Behavioral Trajectories

ERIC Educational Resources Information Center

Thompson, Richard; Tabone, Jiyoung Kim; Litrownik, Alan J.; Briggs, Ernestine C.; Hussey, Jon M.; English, Diana J.; Dubowitz, Howard

2011-01-01

Little is known about the early childhood indicators of adolescent risk. The link between trajectories of externalizing behavioral problems and early adolescent risk behavior was examined in a longitudinal sample of 875 child participants in the LONGSCAN studies. Five trajectory groups of children defined by externalizing behavior problems were…

Dementia - behavior and sleep problems

MedlinePlus

... gov/ency/patientinstructions/000029.htm Dementia - behavior and sleep problems To use the sharing features on this ... sleep and stay asleep Tips for Behavior and Sleep Problems Having a daily routine may help. Calmly ...

Ethical Relativism and Behavior Therapy.

ERIC Educational Resources Information Center

Kitchener, Richard F.

1980-01-01

Argues that behavior therapists are really ethical relativists and sometimes ethical skeptics. Ethical naturalism found in operant behavior therapy does entail ethical relativism. Other authors respond to these views. (Author)

Antecedent influences on behavior disorders.

PubMed Central

Smith, R G; Iwata, B A

1997-01-01

The influence of antecedent events on behavior disorders has been relatively understudied by applied behavior analysts. This lack of research may be due to a focus on consequences as determinants of behavior and a historical disagreement on a conceptual framework for describing and interpreting antecedent variables. We suggest that antecedent influences can be described using terms derived from basic behavioral principles and that their functional properties can be adequately interpreted as discriminative and establishing operations. A set of studies on assessment and treatment of behavior disorders was selected for review based on their relevance to the topic of antecedent events. These studies were categorized as focusing on assessment of antecedent events, antecedent treatments for behavior disorders maintained by either positive or negative reinforcement, and special cases of antecedent events in behavior disorders. Some directions for future research on antecedent influences in the analysis and treatment of behavior disorders are discussed. PMID:9210312

Habit and Behavioral Intentions as Predictors of Social Behavior.

PubMed

Landis, Dan; Triandis, Harry C; Adamopoulos, John

1978-12-01

This research assessed the relative impact of habit and behavioral intentions in predicting classroom teacher behavior, using a model proposed by Triandis. Responses from a behavioral differential, as well as two hours of classroom observations, were taken on 77 male and female black and white junior high school teachers. The classroom observation technique (STOIC) obtained the frequencies of emitted behaviors (both verbal and nonverbal), categorized by race and sex of the target child. Results indicated that habit was a more potent predictor of classroom behavior than intentions. However, a post-hoc analysis supported the notion that intentions become important when the habit component can be suppressed.

Nurses' Spirituality Improves Caring Behavior

ERIC Educational Resources Information Center

Bakar, Abu; Nursalam; Adriani, Merryana; Kusnanto; Qomariah, Siti Nur; Hidayati, Laily; Pratiwi, Ika Nur; Ni'mah, Lailatun

2017-01-01

Caring is a behavior of giving holistic assistance to individuals. In fact, this important behavior still has not routinely performed in current nursing practice. Personality and sipirituality are important factors in forming one's caring behavior. Spirituality is a passion or impulse to perform noble action. The objective of this study was to…

Behavior Management in Afterschool Settings

ERIC Educational Resources Information Center

Mahoney, Joseph L.

2014-01-01

Although behavioral management is one of the most challenging aspects of working in an afterschool setting, staff do not typically receive formal training in evidence-based approaches to handling children's behavior problems. Common approaches to behavioral management such as punishment or time-out are temporary solutions because they do not…

Behavior Plan, Does It Work?

ERIC Educational Resources Information Center

Gonzalez, Blanca M.; Brown, D.

2015-01-01

As educators, we are responsible for teaching academic skills. However, some students not only need to learn academic skills but they need behavior support, due to problematic behaviors that are happening in the school setting. In this article, we will learn more of what are the implications, requirements and best strategies for a behavior plan.…

BEHAVIORAL TECHNOLOGY AND MANPOWER DEVELOPMENT.

ERIC Educational Resources Information Center

COOK, DONALD A.; MECHNER, FRANCIS

A BRIEF HISTORIC SURVEY WHICH PLACES PROGRAMED INSTRUCTION IN THE PROPER PERSPECTIVE RELATIVE TO BEHAVIORAL TECHNOLOGY AS A WHOLE IS PRESENTED. BEHAVIORAL TECHNOLOGY IS THE APPLICATION OF LEARNING THEORY TO PRACTICAL PROBLEMS OF TRAINING AND EDUCATION. THE APPLICATION OF BEHAVIORAL TECHNOLOGY TO THE TEACHING OF CERTAIN VERBAL AND INTELLECTUAL…

Behavior: My Problem or Yours?

ERIC Educational Resources Information Center

Trede, Mildred

1991-01-01

Activities are described for learning about problem classroom behaviors, the impact of one's manner of attire on one's behavior, and personal responsibility for one's behavior. Learning activities include role playing, making math puzzles, writing personal anecdotes, drawing a persuasive cartoon concerning smoking and discipline, and making bar…

Risky Behavior, Ecstasy, and Education

ERIC Educational Resources Information Center

Callier, Heather H.

2011-01-01

Ecstasy is a risky behavior that continues to be a concern in the education system today. The review of the Ecstasy literature focused on the definition of risky behavior, prevalence, and other basis aspects of Ecstasy; discovering life events that are associated with Ecstasy use, the function of this behavior, interventions for substance abuse,…

Factors Effecting Undergraduate Leadership Behaviors

ERIC Educational Resources Information Center

Gallagher, Margie Lee; Marshall, Jeffrey C.; Pories, Mary Lisa; Daughety, Morgan

2014-01-01

Leadership behaviors of undergraduates (n = 1,103) were examined using the Student Leadership Practice Inventory (SLPI). The practice of leadership behaviors increased significantly from freshman to juniors and from juniors to seniors. However, each class was significantly less likely to practice the Challenge the Process behavior and…

Adolescent Suicide and Suicidal Behavior

ERIC Educational Resources Information Center

Bridge, Jeffrey A.; Goldstein, Tina R.; Brent, David A.

2006-01-01

This review examines the descriptive epidemiology, and risk and protective factors for youth suicide and suicidal behavior. A model of youth suicidal behavior is articulated, whereby suicidal behavior ensues as a result of an interaction of socio-cultural, developmental, psychiatric, psychological, and family-environmental factors. On the basis of…

Problem Behaviors & Tourette Syndrome. Revised.

ERIC Educational Resources Information Center

Bruun, Ruth Dowling; And Others

This pamphlet discusses behavioral problems which are sometimes associated with Tourette Syndrome (TS), along with suggestions for parents to help manage these behaviors. Consideration is given to the following problems: obsessive-compulsive symptoms; attention deficit hyperactivity disorder; aggressive and explosive behaviors; self-injurious…

Disturbing Behavior Checklists" Technical Manual

ERIC Educational Resources Information Center

Algozzine, Bob

2012-01-01

Ecological theorists have suggested that "disturbance" may result from an interaction between a child's behavior and reactions to that behavior within ecosystems such as schools. In this context, behavior is viewed as "disturbing" rather than "disturbed" and equal emphasis is given to the child and to individuals with whom the child interacts when…

Counselors' Perceptions of Ethical Behaviors

ERIC Educational Resources Information Center

Neukrug, Edward S.; Milliken, Tammi

2011-01-01

A random sample of American Counseling Association members was asked to respond to a 77-item survey of counselor behaviors and identify whether each behavior was ethical or unethical. Results are categorized by behaviors in which 90% of counselors agreed, 75% to 90% agreed, and 25% to 50% disagreed. Also, changes in ethics education were reviewed…

Changing Health Behavior in Youth

ERIC Educational Resources Information Center

Hochbaum, Godfrey M.

2010-01-01

In this article, the author considers the need for changing health behavior in youth. The author begins by discussing how people learn health behavior which could help educators in understanding the reasons why it is often difficult to effect changes--and how educators may succeed. If the aim of health educators is to change behavior, the author…

Falling Barometer--Failing Behavior.

ERIC Educational Resources Information Center

Scagliotta, Edward G.

1980-01-01

Observations of 127 boys with behavior problems (ages 9 to 13) were made to study the correlation between air pressure and adverse behavior in the Ss. Results showed that, with each change in barometric pressure, there was an obvious change in the Ss' behavior. (PHR)

A Behavioral Theory of Timing.

ERIC Educational Resources Information Center

Killeen, Peter R.; Fetterman, J. Gregor

1988-01-01

A theory of timing is proposed, based on the observation that signals of reinforcement elicit adjunctive behaviors. Transitions between these behaviors are described as a Poisson process. These behaviors may come to serve as the basis for conditional discriminations of the passage of time. (SLD)

Basing assessment and treatment of problem behavior on behavioral momentum theory: Analyses of behavioral persistence.

PubMed

Schieltz, Kelly M; Wacker, David P; Ringdahl, Joel E; Berg, Wendy K

2017-08-01

The connection, or bridge, between applied and basic behavior analysis has been long-established (Hake, 1982; Mace & Critchfield, 2010). In this article, we describe how clinical decisions can be based more directly on behavioral processes and how basing clinical procedures on behavioral processes can lead to improved clinical outcomes. As a case in point, we describe how applied behavior analyses of maintenance, and specifically the long-term maintenance of treatment effects related to problem behavior, can be adjusted and potentially enhanced by basing treatment on Behavioral Momentum Theory. We provide a brief review of the literature including descriptions of two translational studies that proposed changes in how differential reinforcement of alternative behavior treatments are conducted based on Behavioral Momentum Theory. We then describe current clinical examples of how these translations are continuing to impact the definitions, designs, analyses, and treatment procedures used in our clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Behavior change communication strategies.

PubMed

Aggleton, P

1997-04-01

Appropriate and effective communication is central to the success of interventions to reduce the risk of HIV infection. This paper reviews what has been learned about the nature of communication in the behavior change process. It examines the contexts in which communication occurs, as well as the contribution of communication theory, social marketing theory, and structural intervention theory to intervention development. Guidance is offered on the most appropriate ways in which to communicate with different groups and audiences, and future priorities for research and intervention are identified.

Giving behavior of millionaires.

PubMed

Smeets, Paul; Bauer, Rob; Gneezy, Uri

2015-08-25

This paper studies conditions influencing the generosity of wealthy people. We conduct incentivized experiments with individuals who have at least €1 million in their bank account. The results show that millionaires are more generous toward low-income individuals in a giving situation when the other participant has no power, than in a strategic setting, where the other participant can punish unfair behavior. Moreover, the level of giving by millionaires is higher than in any other previous study. Our findings have important implications for charities and financial institutions that deal with wealthy individuals.

Giving behavior of millionaires

PubMed Central

Smeets, Paul; Bauer, Rob; Gneezy, Uri

2015-01-01

This paper studies conditions influencing the generosity of wealthy people. We conduct incentivized experiments with individuals who have at least €1 million in their bank account. The results show that millionaires are more generous toward low-income individuals in a giving situation when the other participant has no power, than in a strategic setting, where the other participant can punish unfair behavior. Moreover, the level of giving by millionaires is higher than in any other previous study. Our findings have important implications for charities and financial institutions that deal with wealthy individuals. PMID:26261327

Nutrition and behavior of lemurs.

PubMed

Junge, Randall E; Williams, Cathy V; Campbell, Jennifer

2009-05-01

Attention to nutritional and behavioral factors is important for appropriate care of lemurs in captivity. Although only a few species are commonly held in captivity, differences between them are important. Knowledge of feeding ecology and natural diet guide nutrition guidelines, as well as management and prevention of common nutrition-related disorders, including obesity, diabetes, and iron-storage disease. Behavioral characteristics that influence captive management are related to social organization, reproductive behavior, territoriality, and infant care. Housing animals in appropriate social groupings in adequately complex environments reduces abnormal behaviors, and addition of enrichment activities and operant conditioning encourages normal behaviors.

Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring

ERIC Educational Resources Information Center

Ogren, Marilee P.; Lombroso, Paul J.

2008-01-01

The article highlights the field of epigenetics and its relevance in determining the effects of maternal nurturing on behavioral patterns in offsprings. Results concluded that maternal behavior influences the offspring's behavior to stress in adulthood and the effects are transgenerational through epigenetic mechanisms.

[Terrorism and human behavior].

PubMed

Leistedt, S J

2018-04-01

Theories of religion are essential for understanding current trends in terrorist activities. The aim of this work is to clarify religion's role in facilitating terror and outline in parallel with recent theoretical developments on terrorism and human behaviour. Several databases were used such as PubCentral, Scopus, Medline and Science Direct. The search terms "terrorism", "social psychology", "religion", "evolution", and "cognition" were used to identify relevant studies in the databases. This work examines, in a multidimensional way, how terrorists employ these features of religion to achieve their goals. In the same way, it describes how terrorists use rituals to conditionally associate emotions with sanctified symbols that are emotionally evocative and motivationally powerful, fostering group solidarity, trust, and cooperation. Religious beliefs, including promised rewards in the afterlife, further serve to facilitate cooperation by altering the perceived payoffs of costly actions, including suicide bombing. The adolescent pattern of brain development is unique, and young adulthood presents an ideal developmental stage to attract recruits and enlist them in high-risk behaviors. This work offers insights, based on this translational analysis, concerning the links between religion, terrorism and human behavior. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Role of the trochlear nerve in eye abduction and frontal vision of the red-eared slider turtle (Trachemys scripta elegans).

PubMed

Dearworth, J R; Ashworth, A L; Kaye, J M; Bednarz, D T; Blaum, J F; Vacca, J M; McNeish, J E; Higgins, K A; Michael, C L; Skrobola, M G; Jones, M S; Ariel, M

2013-10-15

Horizontal head rotation evokes significant responses from trochlear motoneurons of turtle that suggests they have a functional role in abduction of the eyes like that in frontal-eyed mammals. The finding is unexpected given that the turtle is generally considered lateral-eyed and assumed to have eye movements instead like that of lateral-eyed mammals, in which innervation of the superior oblique muscle by the trochlear nerve (nIV) produces intorsion, elevation, and adduction (not abduction). Using an isolated turtle head preparation with the brain removed, glass suction electrodes were used to stimulate nIV with trains of current pulses. Eyes were monitored via an infrared camera with the head placed in a gimble to quantify eye rotations and their directions. Stimulations of nIV evoked intorsion, elevation, and abduction. Dissection of the superior oblique muscle identified lines of action and a location of insertion on the eye, which supported kinematics evoked by nIV stimulation. Eye positions in alert behaving turtles with their head extended were compared with that when their heads were retracted in the carapace. When the head was retracted, there was a reduction in interpupillary distance and an increase in binocular overlap. Occlusion of peripheral fields by the carapace forces the turtle to a more frontal-eyed state, perhaps the reason for the action of abduction by the superior oblique muscle. These findings support why trochlear motoneurons in turtle respond in the same way as abducens motoneurons to horizontal rotations, an unusual characteristic of vestibulo-ocular physiology in comparison with other mammalian lateral-eyed species. Copyright © 2013 Wiley Periodicals, Inc.

Compendium of crane behavior. Part 1: Individual (nonsocial) behavior

USGS Publications Warehouse

Ellis, D.H.; Archibald, George W.; Swengel, S.R.; Kepler, C.B.; Harris, James

1991-01-01

This paper provides the organizational framework, nomenclature, and abbreviated descriptions for all conspicuous nonsocial behavioral units for all 15 species of crane. We present eight generalized functional classes of behavior. These classes include about 90 discrete motor patterns that constitute the nonsocial repertoire of all cranes. We present this compendium to facilitate information exchanges among students of crane behavior and to encourage interest in future detailed studies of the descriptive ethology of each species.

Behavioral intervention reduces unhealthy eating behaviors in preschool children via a behavior card approach.

PubMed

Lin, Ming; Pan, Li-Ping; Han, Juan; Li, Li; Jiang, Jing-Xiong; Jin, Run-Ming

2016-12-01

Many eating behaviors form in childhood, and some unhealthy behaviors may persist into adulthood and have potential impacts on people's health. This study evaluated the effectiveness of behavioral intervention in reducing consumption of Western fast food, sweetened beverages, fried food in preschool children, and changing parents' rewarding behaviors that encourage the consumption of the unhealthy foods. The research was a cluster randomized trial of seven kindergartens, involving 1138 children aged 3-6 years and their parents in Beijing, China. Parents and children allocated to the intervention group received two lectures and printed resources, including behavior cards, educational sheets. Children's behavior cards, applied with behavior-changing techniques, were used to intervene, and monitor behavior changes over time. Children in the control group just followed their usual health education curriculum in kindergartens. Intervention effects on food consumption behaviors were assessed by examining pre- and post-questionnaires. Of the 1138 children screened at baseline, 880 (77.3%) were measured at the end of the intervention period. The intervention lasted from March to June in 2010. The results showed that consumption of Western fast food, sweetened beverages, and fried food was decreased among the intervention group (P<0.001). Proportions of parents using Western fast food as rewards for their children were decreased (P=0.002). From March to June 2010, the frequency of each target behavior in children tended to decrease over the intervention period (P<0.001). Most parents favored regularly-delivered behavior cards or materials for behavioral intervention. In conclusion, the behavioral intervention encourages the healthier eating behaviors of children and reduces the parents' practice of using unhealthy foods as reward.

Explaining Moral Behavior.

PubMed

Osman, Magda; Wiegmann, Alex

2017-03-01

In this review we make a simple theoretical argument which is that for theory development, computational modeling, and general frameworks for understanding moral psychology researchers should build on domain-general principles from reasoning, judgment, and decision-making research. Our approach is radical with respect to typical models that exist in moral psychology that tend to propose complex innate moral grammars and even evolutionarily guided moral principles. In support of our argument we show that by using a simple value-based decision model we can capture a range of core moral behaviors. Crucially, the argument we propose is that moral situations per se do not require anything specialized or different from other situations in which we have to make decisions, inferences, and judgments in order to figure out how to act.

Neuropeptides, Microbiota, and Behavior.

PubMed

Holzer, P

2016-01-01

The gut microbiota and the brain interact with each other through multiple bidirectional signaling pathways in which neuropeptides and neuroactive peptide messengers play potentially important mediator roles. Currently, six particular modes of a neuropeptide link are emerging. (i) Neuropeptides and neurotransmitters contribute to the mutual microbiota-host interaction. (ii) The synthesis of neuroactive peptides is influenced by microbial control of the availability of amino acids. (iii) The activity of neuropeptides is tempered by microbiota-dependent autoantibodies. (iv) Peptide signaling between periphery and brain is modified by a regulatory action of the gut microbiota on the blood-brain barrier. (v) Within the brain, gut hormones released under the influence of the gut microbiota turn into neuropeptides that regulate multiple aspects of brain activity. (vi) Cerebral neuropeptides participate in the molecular, behavioral, and autonomic alterations which the brain undergoes in response to signals from the gut microbiota. © 2016 Elsevier Inc. All rights reserved.

Behavior analytic approaches to problem behavior in intellectual disabilities.

PubMed

Hagopian, Louis P; Gregory, Meagan K

2016-03-01

The purpose of the current review is to summarize recent behavior analytic research on problem behavior in individuals with intellectual disabilities. We have focused our review on studies published from 2013 to 2015, but also included earlier studies that were relevant. Behavior analytic research on problem behavior continues to focus on the use and refinement of functional behavioral assessment procedures and function-based interventions. During the review period, a number of studies reported on procedures aimed at making functional analysis procedures more time efficient. Behavioral interventions continue to evolve, and there were several larger scale clinical studies reporting on multiple individuals. There was increased attention on the part of behavioral researchers to develop statistical methods for analysis of within subject data and continued efforts to aggregate findings across studies through evaluative reviews and meta-analyses. Findings support continued utility of functional analysis for guiding individualized interventions and for classifying problem behavior. Modifications designed to make functional analysis more efficient relative to the standard method of functional analysis were reported; however, these require further validation. Larger scale studies on behavioral assessment and treatment procedures provided additional empirical support for effectiveness of these approaches and their sustainability outside controlled clinical settings.

An opinion-driven behavioral dynamics model for addictive behaviors

DOE PAGES

Moore, Thomas W.; Finley, Patrick D.; Apelberg, Benjamin J.; ...

2015-04-08

We present a model of behavioral dynamics that combines a social network-based opinion dynamics model with behavioral mapping. The behavioral component is discrete and history-dependent to represent situations in which an individual’s behavior is initially driven by opinion and later constrained by physiological or psychological conditions that serve to maintain the behavior. Additionally, individuals are modeled as nodes in a social network connected by directed edges. Parameter sweeps illustrate model behavior and the effects of individual parameters and parameter interactions on model results. Mapping a continuous opinion variable into a discrete behavioral space induces clustering on directed networks. Clusters providemore » targets of opportunity for influencing the network state; however, the smaller the network the greater the stochasticity and potential variability in outcomes. Furthermore, this has implications both for behaviors that are influenced by close relationships verses those influenced by societal norms and for the effectiveness of strategies for influencing those behaviors.« less

Does Early Childhood Callous-Unemotional Behavior Uniquely Predict Behavior Problems or Callous-Unemotional Behavior in Late Childhood?

ERIC Educational Resources Information Center

Waller, Rebecca; Dishion, Thomas J.; Shaw, Daniel S.; Gardner, Frances; Wilson, Melvin N.; Hyde, Luke W.

2016-01-01

Callous-unemotional (CU) behavior has been linked to behavior problems in children and adolescents. However, few studies have examined whether CU behavior in "early childhood" predicts behavior problems or CU behavior in "late childhood". This study examined whether indicators of CU behavior at ages 2-4 predicted aggression,…

Sexual Behavior in Germany.

PubMed

Haversath, Julia; Gärttner, Kathrin M; Kliem, Sören; Vasterling, Ilka; Strauss, Bernhard; Kröger, Christoph

2017-08-21

There have not been any population-based surveys in Germany to date on the frequency of various types of sexual behavior. The topic is of interdisciplinary interest, particularly with respect to the prevention and treatment of sexually transmitted infections. Within the context of a survey that dealt with multiple topics, information was obtained from 2524 persons about their sexual orientation, sexual practices, sexual contacts outside relationships, and contraception. Most of the participating women (82%) and men (86%) described themselves as heterosexual. Most respondents (88%) said they had engaged in vaginal intercourse at least once, and approximately half said they had engaged in oral intercourse at least once (either actively or passively). 4% of the men and 17% of the women said they had been the receptive partner in anal intercourse at least once. 5% of the respondents said they had had unprotected sexual intercourse outside their primary partnership on a single occasion, and 8% said they had done so more than once; only 2% of these persons said they always used a condom during sexual intercourse with their primary partner. Among persons reporting unprotected intercourse outside their primary partnership, 25% said they had undergone a medical examination afterward because of concern about a possible sexually transmitted infection. Among some groups of persons, routine sexual-medicine examinations may help contain the spread of sexually transmitted infections. One component of such examinations should be sensitive questioning about the types of sexual behavior that are associated with a high risk of infection. Information should be provided about the potential modes of transmission, including unprotected vaginal, oral, and anal intercourse outside the primary partnership.

Consistency of Helping-Behavior Measures.

ERIC Educational Resources Information Center

Bar-Tal, Daniel; Raviv, Amiram

1979-01-01

Examines the consistency of various methods of measuring helping behavior. Questionnaires concerning helping behavior among 280 sixth graders and teachers' ratings were compared to measures of altruistic behavior and behavioral intention administered 2 years later. (CM)

Cellular Analogs of Operant Behavior.

DTIC Science & Technology

1992-07-31

confirmed at the behavioral level in parallel studies of hippocampal and intravenous self-administration. The results are consistent with the hypothesis...research is to elucidate the cellular reinforcement mechanisms underlying goal-directed or operant behavior. The specific aim here was to study the... studies and behavioral operant conditioning studies . Most of the research reported was initiated and completed in the present project period. Also

Effective strategies for behavior change.

PubMed

Coleman, Mary Thoesen; Pasternak, Ryan H

2012-06-01

Strategies that are most effective in both prevention and management of chronic disease consider factors such as age, ethnicity, community, and technology. Most behavioral change strategies derive their components from application of the health belief model, the theory of reasoned action/theory of planned behavior, transtheoretical model, and social cognitive theory. Many tools such as the readiness ruler and personalized action plan form are available to assist health care teams to facilitate healthy behavior change. Primary care providers can support behavior changes by providing venues for peer interventions and family meetings and by making new partnerships with community organizations. Copyright © 2012 Elsevier Inc. All rights reserved.

Unobtrusive measures in behavioral assessment

PubMed Central

Kazdin, Alan E.

1979-01-01

A major distinguishing characteristic of behavioral assessment is the direct assessment of overt behavior. Direct assessment is assumed to provide a sample of behavior that reflects client performance in the situation in which behavior is assessed, even if the assessment procedures were not implemented. Yet, in the majority of investigations, behavioral assessment procedures are obtrusive, i.e., subjects are aware that their behavior is being assessed. The potential problem with obtrusive assessment is that it may be reactive, i.e., affect how subjects perform. Recent research has demonstrated that obtrusive observations often are reactive and that behaviors assessed under obtrusive and unobtrusive conditions bear little relation. From methodological and applied perspectives, additional attention needs to be given to unobtrusive measures of behavior change. The present paper illustrates unobtrusive measures in behavior modification including direct observations, archival records, and physical traces of performance. In addition, validation and assessment problems, questions about the obtrusiveness of the measures, and ethical issues are discussed. PMID:16795622

Changing Norms to Change Behavior.

PubMed

Miller, Dale T; Prentice, Deborah A

2016-01-01

Providing people with information about the behavior and attitudes of their peers is a strategy commonly employed by those seeking to reduce behavior deemed harmful either to individuals (e.g., high alcohol consumption) or the collective (e.g., high energy consumption). We review norm-based interventions, detailing the logic behind them and the various forms they can take. We give special attention to interventions designed to decrease college students' drinking and increase environment-friendly behaviors. We identify the conditions under which norm information has the highest likelihood of changing the targeted behavior and discuss why this is the case.

The Attitude-Behavior Linkage in Behavioral Cascades

ERIC Educational Resources Information Center

Friedkin, Noah E.

2010-01-01

The assumption that individual behavior has an antecedent evaluative foundation is an important component of theories in sociology, psychology, political science, and economics. In its simplest form, the antecedent evaluation is a positive or negative attitude toward an object that may affect an individual's object-related behavior. This attitude…

Parent Behavior Importance and Parent Behavior Frequency Questionnaires: Psychometric Characteristics

ERIC Educational Resources Information Center

Mowder, Barbara A.; Sanders, Michelle

2008-01-01

This study examined the psychometric characteristics of two parenting measures: the Parent Behavior Importance Questionnaire (PBIQ) and Parent Behavior Frequency Questionnaire (PBFQ). Both research questionnaires are based on the parent development theory (PDT) and offer parent as well as non-parent respondents the opportunity to rate 38 parenting…

Acceptability of Behavioral Treatments: Influence of Knowledge of Behavioral Principles.

ERIC Educational Resources Information Center

Rasnake, L. Kaye; And Others

1993-01-01

Fifty-seven direct care staff members from an intermediate care facility for adults with mental retardation rated the acceptability of interventions used for self-injurious behavior and completed a measure of knowledge about behavioral principles. Results indicated that staff age and educational attainment were related to knowledge scores, but…

Behavior Modification Project: Reducing and Controlling Calling Out Behaviors.

ERIC Educational Resources Information Center

James, Deborah Anne

The purpose of this study was to determine which behavior modification procedures were the most effective in reducing and controlling the inappropriate calling out behavior of a fifth-grade socially and emotionally disturbed student. Three phases of interventions were involved. As the study began, the resource room instructor was using a behavior…

Is Game Behavior Related to Behavior in Any Other Situation?

ERIC Educational Resources Information Center

McTavish, Jeanne

This paper begins by reviewing previous research concerning the external validity of mixed-motive games as models of international conflict, interpersonal behavior, and behavior in large-scale social dilemmas. Two further experiments are then described, both of which cast further doubt upon the usefulness of such games as models of any real-world…

Use of a Behavioral Graphic Organizer to Reduce Disruptive Behavior

ERIC Educational Resources Information Center

McDaniel, Sara C.; Flower, Andrea

2015-01-01

Students with challenging behavior spend substantial amounts of time away from instruction due to behavioral problems. Time away from instruction reduces their opportunities for learning, which are critical as these students typically demonstrate academic performance below their same-age peers. After removal from instruction due to behavioral…

Behavioral assessment in youth sports: coaching behaviors and children's attitudes.

PubMed

Smith, R E; Zane, N W; Smoll, F L; Coppel, D B

1983-01-01

To define the characteristics and dimensional patterning of coaching behaviors, 15,449 behaviors of 31 youth basketball coaches were coded in terms of a 10-category system. Post-season attitude and self-esteem data were obtained from players on 23 teams and were related to the behavioral measures. Compared with rates of reinforcement, encouragement, and technical instruction, punitive responses occurred relatively infrequently. Factor analysis of the coaching behaviors indicated that supportive and punitive behavioral dimensions were orthogonal or statistically independent of one another rather than opposite ends of the same dimension. Punitive and instructional categories were part of the same behavior cluster. The relationship between coaching behaviors and the various player attitudes were highly specific in nature. Coaching behaviors accounted for about half of the variance in post-season attitudes toward the coach and the sport, but for significantly less variance in measures of team solidarity and self-esteem. Surprisingly, the rate of positive reinforcement was unrelated to any of the attitudinal measures. Punishment was negatively related to liking for the coach. In general, technical instruction categories were the strongest predictors of basketball player attitudes.

[Practice of Behavioral Activation in Cognitive-behavioral Therapy].

PubMed

Kitagawa, Nobuki

2015-01-01

An approach focusing on behavioral activation (BA) was adopted in the cognitive therapy of A. T. Beck, and it came to be considered that BA can play an important role in cognitive-behavioral therapy (CBT) for depression. Therefore, in recent years, BA based on clinical behavior analysis has been developed as a new treatment (Martell, et al.). The core characteristics are as follows: 1) focusing attention on context in daily life to promote the behavior control of patients and avoidance of a hatred experience ; 2) breaking the vicious circle; 3) promoting the behavior according to the purpose that the patients originally expect; 4) recognizing a relationship between behavior and the situation (contingency), thereby recovering self-efficacy tied to the long-term results that one originally expects. This does not increase pleasant activity at random when the patient is inactive, or give a sense of accomplishment. We know that depression is maintained by conducting functional analysis of detailed life behavior, and encourage the patients to have healthy behavior according to individual values. We help them to complete schedules regardless of mood and reflect on the results patiently. It is considered that those processes are important. BA may be easy to apply in clinical practice and effective for the chronic cases, or the patients in a convalescent stage. Also, in principle in the CBT for major depression, it may be effective that behavioral activation is provided in an early stage, and cognitive reconstruction in a latter stage. However, an approach to carry out functional analysis by small steps with careful activity monitoring is essential when the symptoms are severe. Furthermore, it should be considered that the way of psychoeducation requires caution because we encourage rest in the treatment of depression in our country. In particular, we must be careful not to take an attitude that an inactive behavior pattern is unproductive only based model cases.

[Environment and addictive behaviors].

PubMed

Touzeau, Didier; Raynal, Marie-Line

2012-12-01

Consumer society creates the emergence of addictive behaviors and environments of the subject "shape" the use of psychoactive substances. The family approach is to search out a guilt of members to understand family dynamics and enable young people to emancipate themselves from the family model. The social environment contributes to the marginalization of drug users "pathologizing" his conduct. Offer help without preconditions and a relationship based on a therapeutic alliance can contribute decisively to the recovery of an addict. The prison is a place of initiation of use and consumption of psychoactive substances despite the offer of specialized treatment. Measures of risk reduction of HCV/HIV infection and alternatives to incarceration should complete it. At workplace, consumption can be considered as a mean of doping to be more "efficient", but also as an attempt to withstand the stresses and changes in working conditions in the context of individualization and a loss of marks related to the new way of organizing work. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Stress and Eating Behaviors

PubMed Central

Yau, Yvonne H. C.; Potenza, Marc N.

2014-01-01

Obesity is a heterogeneous construct that, despite multiple and diverse attempts, has been difficult to treat. One conceptualization gaining media and research attention in recent years is that foods, particularly hyperpalatable (e.g., high-fat, high sugar) ones, may possess addictive qualities. Stress is an important factor in the development of addiction and in addiction relapse, and may contribute to an increased risk for obesity and other metabolic diseases. Uncontrollable stress changes eating patterns and the salience and consumption of hyperpalatable foods; over time, this could lead to changes in allostatic load and trigger neurobiological adaptations that promote increasingly compulsively behavior. This association may be mediated by alterations in the hypothalamic-pituitary-adrenal (HPA) axis, glucose metabolism, insulin sensitivity, and other appetite-related hormones and hypothalamic neuropeptides. At a neurocircuitry level, chronic stress may affect the mesolimbic dopaminergic system and other brain regions involved in stress/motivation circuits. Together, these may synergistically potentiate reward sensitivity, food preference, and the wanting and seeking of hyperpalatable foods, as well as induce metabolic changes that promote weight and body fat mass. Individual differences in susceptibility to obesity and types of stressors may further moderate this process. Understanding the associations and interactions between stress, neurobiological adaptations, and obesity is important in the development of effective prevention and treatment strategies for obesity and related metabolic diseases. PMID:24126546

[Neurobiology of addictive behavior].

PubMed

Ivlieva, N Iu

2011-01-01

Addictive behavior developes after repeated substance use and it typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to the drug use than to other activities. Relapse, the resumption of drug taking after periods of abstinence, remains the major problem for the treatment of addiction. The process of drug addiction shares striking commonalities with neural plasticity associated with natural reward learning and memory and is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. The switch from controlled to compulsive drug seeking represents a transition at the neural level from prefrontal cortical to striatal control. Current neurophysiologic evidence suggests that the development of addiction is to some extent due to neurochemical stimulation of the midbrain dopaminergic system that is traditionally considered as a 'common neural currency' for rewards of most kinds. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity. Environmental factors are crucial in addiction vulnerability and resistese too.

Heat pipe dynamic behavior

NASA Technical Reports Server (NTRS)

Issacci, F.; Roche, G. L.; Klein, D. B.; Catton, I.

1988-01-01

The vapor flow in a heat pipe was mathematically modeled and the equations governing the transient behavior of the core were solved numerically. The modeled vapor flow is transient, axisymmetric (or two-dimensional) compressible viscous flow in a closed chamber. The two methods of solution are described. The more promising method failed (a mixed Galerkin finite difference method) whereas a more common finite difference method was successful. Preliminary results are presented showing that multi-dimensional flows need to be treated. A model of the liquid phase of a high temperature heat pipe was developed. The model is intended to be coupled to a vapor phase model for the complete solution of the heat pipe problem. The mathematical equations are formulated consistent with physical processes while allowing a computationally efficient solution. The model simulates time dependent characteristics of concern to the liquid phase including input phase change, output heat fluxes, liquid temperatures, container temperatures, liquid velocities, and liquid pressure. Preliminary results were obtained for two heat pipe startup cases. The heat pipe studied used lithium as the working fluid and an annular wick configuration. Recommendations for implementation based on the results obtained are presented. Experimental studies were initiated using a rectangular heat pipe. Both twin beam laser holography and laser Doppler anemometry were investigated. Preliminary experiments were completed and results are reported.

Hygrothermal behavior of polybenzimidazole

DOE PAGES

Liu, Peng; Mullins, Michael; Bremner, Tim; ...

2016-04-11

Poly[2,2’-(m-phenylene)-5,5’-bibenzimidazole] (PBI) is used in extremely high temperature harsh environment applications. It is a unique engineering material that is formed into parts by powder-sintering at temperatures as high as 500 °C. Recently, ever increasing demands for high temperature polymers have led to significant interest in PBI such that engineering guidelines could be established for its application in high temperature and highly humid environments. The goal of this work was to understand the material science of PBI in hot-wet environments at temperatures up to 288 °C. Thermal gravimetric analysis and mass spectrometry were employed to identify the degraded volatile products. Themore » molecular scale damping behavior of PBI was probed using dynamic mechanical analysis. The changes in tensile properties and fracture toughness due to environmental exposure were also characterized. Upon heating above 250 °C, moisture-containing PBI exhibits obvious molecular structure change. Evidence of crosslinking and degradation is observed. With 288 °C hot water treatment severe degradation of PBI is observed. As a result, fundamental structure-property relationships of PBI affected by these higher temperature, high moisture content environments are discussed.« less

Roger T. Kelleher, Behavior Analyst

ERIC Educational Resources Information Center

Branch, Marc N.

2006-01-01

Roger T. Kelleher, rightly known as one of the foremost contributors to behavioral pharmacology, also made many important contributions to the experimental analysis of behavior. He participated significantly in the development of the discipline, through both his research and his editorial contributions to this journal. This article summarizes his…

Behavioral assessment of personality disorders.

PubMed

Nelson-Gray, R O; Farmer, R F

1999-04-01

This article examines the definition of personality disorders (PDs) from a functional analytical framework and discusses the potential utility of such a framework to account for behavioral tendencies associated with PD pathology. Also reviewed are specific behavioral assessment methods that can be employed in the assessment of PDs, and how information derived from these assessments may be linked to specific intervention strategies.

Mediational Modification of Creative Behaviors.

ERIC Educational Resources Information Center

Russell, Crawford L.

1981-01-01

Adapting the cognitive behavior modification work of Bandura and Mahoney, the author suggests a "mediational approach" to teaching creativity in the art classroom; here the desired behavior is modeled, guided experience is offered for practice, then reward in the form of approval is given for successful completion of the event. (Editor/SJL)

Genes, Environment, and Human Behavior.

ERIC Educational Resources Information Center

Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

Empathy, Communication, and Prosocial Behavior.

ERIC Educational Resources Information Center

Stiff, James B.; And Others

To explain the role of empathy in forms of prosocial behavior, two studies were conducted to examine the relationships among different dimensions of empathy, communication, and prosocial behavior. Study one tested three models hypothesized to explain this process, an altruistic model, an egoistic model, and a dual-process model combining aspects…

Changing Attitudes Through Behavior Modification.

ERIC Educational Resources Information Center

Whipple, W. Scott

This article describes the philosophy and methods used by the staff at the Granite Alternative School in changing student attitudes through behavior modification. The students involved all have a failure syndrome or low self-image, and are dropouts from traditional high schools. Among the techniques used are: (1) reinforcing good behavior (praise…

Learning Behaviors and Learning Spaces

ERIC Educational Resources Information Center

Bennett, Scott

2011-01-01

What specific learning behaviors are important to students and faculty members? Does the campus provide spaces that foster these behaviors? Where are those spaces? Asking these three questions at six colleges and universities reveals notable differences in the ways students and faculty members answer them. Student and faculty member answers also…

The Behavioral Aspects of Smoking.

ERIC Educational Resources Information Center

Krasnegor, Norman A., Ed.

These five papers present a compact summary of current biological, behavioral and psychosocial research on cigarette smoking behavior. They focus especially on the addictive and dependence processes related to smoking and its effects on health. While much is known, recommendations for further research are suggested on topics including: nicotine,…

Evaluating Behavioral Health Surveillance Systems.

PubMed

Azofeifa, Alejandro; Stroup, Donna F; Lyerla, Rob; Largo, Thomas; Gabella, Barbara A; Smith, C Kay; Truman, Benedict I; Brewer, Robert D; Brener, Nancy D

2018-05-10

In 2015, more than 27 million people in the United States reported that they currently used illicit drugs or misused prescription drugs, and more than 66 million reported binge drinking during the previous month. Data from public health surveillance systems on drug and alcohol abuse are crucial for developing and evaluating interventions to prevent and control such behavior. However, public health surveillance for behavioral health in the United States has been hindered by organizational issues and other factors. For example, existing guidelines for surveillance evaluation do not distinguish between data systems that characterize behavioral health problems and those that assess other public health problems (eg, infectious diseases). To address this gap in behavioral health surveillance, we present a revised framework for evaluating behavioral health surveillance systems. This system framework builds on published frameworks and incorporates additional attributes (informatics capabilities and population coverage) that we deemed necessary for evaluating behavioral health-related surveillance. This revised surveillance evaluation framework can support ongoing improvements to behavioral health surveillance systems and ensure their continued usefulness for detecting, preventing, and managing behavioral health problems.

Evaluating Behavioral Health Surveillance Systems

PubMed Central

Azofeifa, Alejandro; Lyerla, Rob; Largo, Thomas; Gabella, Barbara A.; Smith, C. Kay; Truman, Benedict I.; Brewer, Robert D.; Brener, Nancy D.

2018-01-01

In 2015, more than 27 million people in the United States reported that they currently used illicit drugs or misused prescription drugs, and more than 66 million reported binge drinking during the previous month. Data from public health surveillance systems on drug and alcohol abuse are crucial for developing and evaluating interventions to prevent and control such behavior. However, public health surveillance for behavioral health in the United States has been hindered by organizational issues and other factors. For example, existing guidelines for surveillance evaluation do not distinguish between data systems that characterize behavioral health problems and those that assess other public health problems (eg, infectious diseases). To address this gap in behavioral health surveillance, we present a revised framework for evaluating behavioral health surveillance systems. This system framework builds on published frameworks and incorporates additional attributes (informatics capabilities and population coverage) that we deemed necessary for evaluating behavioral health–related surveillance. This revised surveillance evaluation framework can support ongoing improvements to behavioral health surveillance systems and ensure their continued usefulness for detecting, preventing, and managing behavioral health problems. PMID:29752804

Four Investigations of Animal Behavior.

ERIC Educational Resources Information Center

Cheverton, John

1997-01-01

Describes four techniques for investigating animal behavior in situations where it is relatively easy to obtain meaningful data. Presents investigations for attention responses and habituation of domestic animals to sound stimuli, interaction of lambs and ewes, behavior of lambs in a simple T-maze, and vigilance in birds at a feeder. (JRH)

Human Listening: Processes and Behavior.

ERIC Educational Resources Information Center

Weaver, Carl H.

This book is divided into three conceptual areas: a general presentation of listening behavior and its place in the communication process, the major social and psychological processes involved in the selection and cognition of aurally received data, and remedial measures for both the speaker and the auditor. "Listening behavior: an overview"…

Division of Behavioral Health: FAQ

Science.gov Websites

State Employees Behavioral Health DHSS State of Alaska Home Divisions and Agencies Alaska Pioneer Homes Behavioral Health Office of Children's Services Office of the Commissioner Office of Substance Misuse and Addiction Prevention Finance & Management Services Health Care Services Juvenile Justice Public

Biosocial Influences on Fraudulent Behaviors

ERIC Educational Resources Information Center

Beaver, Kevin M.; Holtfreter, Kristy

2009-01-01

A wealth of empirical research has revealed that antisocial behavioral phenotypes result from genetic and environmental factors working independently and interactively. However, much of this research has focused on traditional forms of antisocial behavior, such as aggression and violence. At the same time, research has been slow to examine whether…

The structure of recreation behavior

Treesearch

Thomas A. More; James R. Averill

2003-01-01

We present a meta-theoretical analysis of recreation concepts as an argument about organizing and explaining recreation behavior. Recreation activities are behavioral constructions that people build from both prototypic subsystems (those present in virtually all instances of the activity) and design subsystems (optional subsystems that adapt the activity to serve...

Reactive Behavior Patterns Go Online.

ERIC Educational Resources Information Center

Dziuban, Charles D.; Moskal, Patsy D.; Dziuban, Emily K.

2000-01-01

Surveys of all online students at the University of Central Florida during summer 1997 and spring 1998 provided 381 useable survey instruments assessing learner reactive behavior patterns with the Long-Dziuban Reactive Behavior Protocol. Results indicated that students in online courses tended not to be the independent learners. (PGS)

Depression, Pain, and Pain Behavior.

ERIC Educational Resources Information Center

Keefe, Francis J.; And Others

1986-01-01

Examined the degree to which depression predicted pain and pain behavior. The Beck Depression Inventory was administered to 207 low back pain patients. Depression and physical findings were the most important predictors of pain and pain behavior. Depression proved significant even after controlling for important demographic and medical status…

A Behavioral Conceptualization of Aphasia

ERIC Educational Resources Information Center

Baker, Jonathan C.; LeBlanc, Linda A.; Raetz, Paige B.

2008-01-01

Aphasia is an acquired language impairment that affects over 1 million individuals, the majority of whom are over age 65 (Groher, 1989). This disorder has typically been conceptualized within a cognitive neuroscience framework, but a behavioral interpretation of aphasia is also possible. Skinner's (1957) analysis of verbal behavior proposes a…

Neuroscientific Measures of Covert Behavior

ERIC Educational Resources Information Center

Ortu, Daniele

2012-01-01

In radical behaviorism, the difference between overt and covert responses does not depend on properties of the behavior but on the sensitivity of the measurement tools employed by the experimenter. Current neuroscientific research utilizes technologies that allow measurement of variables that are undetected by the tools typically used by behavior…

Salmonid behavior and water temperature

Treesearch

Sally T. Sauter; John McMillan; Jason B. Dunham

2001-01-01

Animals react not only to immediate changes in their environment but also to cues that signal long-term changes to which they must adapt to survive. A proximate factor stimulates an animal’s immediate behavioral response, whereas what is known as an ultimate factor causes an animal to adjust its behavior to evolving conditions, thereby increasing its fitness and...

Sniffing behavior communicates social hierarchy.

PubMed

Wesson, Daniel W

2013-04-08

Sniffing is a specialized respiratory behavior that is essential for the acquisition of odors [1-4]. Perhaps not independent of this, sniffing is commonly displayed during motivated [5-7] and social behaviors [8, 9]. No measures of sniffing among interacting animals are available, however, calling into question the utility of this behavior in the social context. From radiotelemetry recordings of nasal respiration, I found that investigation by one rat toward the facial region of a conspecific often elicits a decrease in sniffing frequency in the conspecific. This reciprocal display of sniffing was found to be dependent upon the rat's social status in two separate paradigms, with subordinates reliably decreasing their sniffing frequency upon being investigated in the face by dominant rats. Failure of subordinates to decrease their sniffing frequency shortened the latency for agonistic behavior by dominant rats, reflecting that decreases in sniffing serve as appeasement signals during social interactions. Rats rendered unable to smell persisted in displaying reciprocal sniffing behavior, demonstrating the independence of this behavior from olfaction. Oxytocin treatment in rats with established social hierarchies abolished agonistic behaviors and reciprocal sniffing displays. Together, these findings demonstrate that rodents utilize sniffing behaviors communicatively, not only to collect [6, 10-14] but also to convey information. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inventory behavior at remote sites

NASA Technical Reports Server (NTRS)

Lewis, William C., Jr.

1987-01-01

An operations research study was conducted concerning inventory behavior on the space station. Historical data from the Space Shuttle was used. The results demonstrated a high logistics burden if Space Shuttle reliability technology were to be applied without modification to space station design (which it was not). Effects of rapid resupply and on board repair capabilities on inventory behavior were investigated.

Pathways of Adolescent Suicidal Behavior.

ERIC Educational Resources Information Center

Munzer, Jane; And Others

Suicide attempts and suicidal ideation among adolescents have been increasing faster than those for adults. This study addresses three questions on adolescent suicidal behavior: (1) Why do some adolescents with psychiatric disorders have a history of suicidal behaviors and some do not?; (2) How do intrapsychic and interpersonal underpinnings of…

Validating Measures of Brinkmanship Behaviors.

ERIC Educational Resources Information Center

Melancon, Janet G.; Thompson, Bruce

This study investigated the validity of measures of teacher brinkmanship behaviors. These are behaviors which challenge the authority system of the school while avoiding its negative sanctions. These acts are generally satirical in nature. The subjects were teachers and principals representing schools located in a metropolitan school system in the…

Estimating wildfire behavior and effects

Treesearch

Frank A. Albini

1976-01-01

This paper presents a brief survey of the research literature on wildfire behavior and effects and assembles formulae and graphical computation aids based on selected theoretical and empirical models. The uses of mathematical fire behavior models are discussed, and the general capabilities and limitations of currently available models are outlined.

Perceptions of Teacher Brinkmanship Behaviors.

ERIC Educational Resources Information Center

Melancon, Jan G.; Thompson, Bruce

Brinkmanship behaviors are challenges to authority expressed in such a mannner that expected negative sanctions are typically avoided. They are usually extemporaneous, involve satire or sarcasm, and take place in front of an audience. This study investigated 43 principals' and 137 teachers' perceptions of teacher brinkmanship behaviors and sought…

Handbook of Applied Behavior Analysis

ERIC Educational Resources Information Center

Fisher, Wayne W., Ed.; Piazza, Cathleen C., Ed.; Roane, Henry S., Ed.

2011-01-01

Describing the state of the science of ABA, this comprehensive handbook provides detailed information about theory, research, and intervention. The contributors are leading ABA authorities who present current best practices in behavioral assessment and demonstrate evidence-based strategies for supporting positive behaviors and reducing problem…

Suicidal Behavior among Early Adolescents.

ERIC Educational Resources Information Center

Gover, F. Jill

There is a great deal of concern about teenage suicide. This study obtained a prevalence rate of suicidal behaviors among non-psychiatric early adolescents (ages 11-16) and investigated personal and family variables that may characterize the young teenagers who report varying degrees of suicidal behavior. A self-report questionnaire was…

Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment.

PubMed

Dorfman, Verónica Berta; Rey-Funes, Manuel; Bayona, Julio César; López, Ester María; Coirini, Héctor; Loidl, César Fabián

2009-04-01

Perinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full-term fetuses in a water bath at 37 degrees C for 19 or 20 min (PA19 or PA20) or at 15 degrees C for 20 min (hypothermia during PA-HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA-HPA). Full-term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60-day-old PA20 rats, with increased NADPH-d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH-d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia.

Pollen Processing Behavior of Heliconius Butterflies: A Derived Grooming Behavior

PubMed Central

Hikl, Anna-Laetitia; Krenn, Harald W.

2011-01-01

Pollen feeding behaviors Heliconius and Laparus (Lepidoptera: Nymphalidae) represent a key innovation that has shaped other life history traits of these neotropical butterflies. Although all flower visiting Lepidoptera regularly come in contact with pollen, only Heliconius and Laparus butterflies actively collect pollen with the proboscis and subsequently take up nutrients from the pollen grains. This study focused on the behavior of pollen processing and compared the movement patterns with proboscis grooming behavior in various nymphalid butterflies using video analysis. The proboscis movements of pollen processing behavior consisted of a lengthy series of repeated coiling and uncoiling movements in a loosely coiled proboscis position combined with up and down movements and the release of saliva. The proboscis-grooming behavior was triggered by contamination of the proboscis in both pollen feeding and non-pollen feeding nymphalid butterflies. Proboscis grooming movements included interrupted series of coiling and uncoiling movements, characteristic sideways movements, proboscis lifting, and occasionally full extension of the proboscis. Discharge of saliva was more pronounced in pollen feeding species than in non-pollen feeding butterfly species. We conclude that the pollen processing behavior of Heliconius and Laparus is a modified proboscis grooming behavior that originally served to clean the proboscis after contamination with particles. PMID:22208893

Behavioral variability in an evolutionary theory of behavior dynamics.

PubMed

Popa, Andrei; McDowell, J J

2016-03-01

McDowell's evolutionary theory of behavior dynamics (McDowell, 2004) instantiates populations of behaviors (abstractly represented by integers) that evolve under the selection pressure of the environment in the form of positive reinforcement. Each generation gives rise to the next via low-level Darwinian processes of selection, recombination, and mutation. The emergent patterns can be analyzed and compared to those produced by biological organisms. The purpose of this project was to explore the effects of high mutation rates on behavioral variability in environments that arranged different reinforcer rates and magnitudes. Behavioral variability increased with the rate of mutation. High reinforcer rates and magnitudes reduced these effects; low reinforcer rates and magnitudes augmented them. These results are in agreement with live-organism research on behavioral variability. Various combinations of mutation rates, reinforcer rates, and reinforcer magnitudes produced similar high-level outcomes (equifinality). These findings suggest that the independent variables that describe an experimental condition interact; that is, they do not influence behavior independently. These conclusions have implications for the interpretation of high levels of variability, mathematical undermatching, and the matching theory. The last part of the discussion centers on a potential biological counterpart for the rate of mutation, namely spontaneous fluctuations in the brain's default mode network. © 2016 Society for the Experimental Analysis of Behavior.

Understanding proenvironmental intentions and behaviors: The importance of considering both the behavior setting and the type of behavior.

PubMed

Maki, Alexander; Rothman, Alexander J

2017-01-01

To better understand the consistency of people's proenvironmental intentions and behaviors, we set out to examine two sets of research questions. First, do people perform (1) different types of proenvironmental behaviors consistently, and (2) the same proenvironmental behavior consistently across settings? Second, are there consistent predictors of proenvironmental behavioral intentions across behavior and setting type? Participants reported four recycling and conservation behaviors across three settings, revealing significant variability in rates of behaviors across settings. Prior behavior, attitudes toward the behavior, and importance of the behaviour consistently predicted proenvironmental intentions. However, perceived behavioral control tended to predict intentions to perform proenvironmental behavior outside the home. Future research aimed at understanding and influencing different proenvironmental behaviors should carefully consider how settings affect intentions and behavior.

Behavioral aspects of development of eating behavior and nutrition status.

PubMed

Vazir, Shahnaz

2002-05-01

Studies on the development of eating behavior in rural India indicated that mothers of young children made food choices that fit into their budgets, and were also influenced by new information. Their choices were still immersed in traditional beliefs, some of which had positive effects on nutrition. Specific childrearing behaviors influenced positive deviance in the growth and psychosocial development of infants and preschoolers. A life-cycle approach to the development of eating behavior that deciphers needs at each stage and linkages between stages is necessary. Cost-benefit needs to be considered when devising strategies for future intervention programs.

Bridging Behavioral Assessment and Behavioral Intervention: Finding Your Inner Behavior Analyst

ERIC Educational Resources Information Center

Johnson, LeAnne D.; Monn, Emily

2015-01-01

The persistence of challenging behaviors for some children highlights a need and an opportunity to explore several key principles of behavioral intervention that are necessary for effective decision- making when more personalized interventions must be layered on top of high-quality universal supports. In the absence of expert support,…

The behavioral economics of violence.

PubMed

Rachlin, Howard

2004-12-01

From the viewpoint of teleological behaviorism the first question to ask in attempting to understand any behavior, including violent behavior, is: What are its contingencies of reward and punishment? Or, to put the question in economic terms: What are the short-term and long-term costs and benefits that such behavior entails? Let us therefore consider the costs and benefits of youth violence. Among the short-term costs of violent behavior are the physical effort of the act, the possibility of immediate physical retaliation, immediate social disapproval, and the opportunity cost of other social acts that the violent behavior takes the place of (you can't be affectionate and violent at the same time, for instance). Among the immediate benefits of violent behavior are the intrinsic satisfaction of the violent act itself and any extrinsic benefit; if A violently appropriates B's new sneakers then obtaining the sneakers reinforces A's violence. These immediate benefits may well outweigh the costs in many contexts. Among the long-term costs of violent behavior are delayed retaliation, possible social disapproval and loss of social support, rejection from a social group, job loss, and health risks associated with a violent lifestyle. Among the long-term benefits are long-term intimidation of others (your neighbor is less likely to build a fence on your property if you have a reputation for violence), and a possibly exciting lifestyle. These long-term benefits may well be outweighed by the long-term costs. Opposition of long-term net costs to short-term net benefits, where it exists, creates a personal self-control trap: Overall satisfaction may decrease monotonically with rate of the target behavior but, regardless of its rate, the immediate satisfaction of doing it is always higher than that of not doing it. In the case of violent behavior, this trap is exacerbated by the fact that as a person's violence increases, net immediate reinforcement also increases (due to

Behavioral dimensions of food security

PubMed Central

Timmer, C. Peter

2012-01-01

The empirical regularities of behavioral economics, especially loss aversion, time inconsistency, other-regarding preferences, herd behavior, and framing of decisions, present significant challenges to traditional approaches to food security. The formation of price expectations, hoarding behavior, and welfare losses from highly unstable food prices all depends on these behavioral regularities. At least when they are driven by speculative bubbles, market prices for food staples (and especially for rice, the staple food of over 2 billion people) often lose their efficiency properties and the normative implications assigned by trade theory. Theoretical objections to government efforts to stabilize food prices, thus, have reduced saliency, although operational, financing, and implementation problems remain important, even critical. The experience of many Asian governments in stabilizing their rice prices over the past half century is drawn on in this paper to illuminate both the political mandates stemming from behavioral responses of citizens and operational problems facing efforts to stabilize food prices. Despite the theoretical problems with free markets, the institutional role of markets in economic development remains. All policy instruments must operate compatibly with prices in markets. During policy design, especially for policies designed to alter market prices, incentive structures need to be compatible with respect to both government capacity (bureaucratic and budgetary) and empirical behavior on the part of market participants who will respond to planned policy changes. A new theoretical underpinning to political economy analysis is needed that incorporates this behavioral perspective, with psychology, sociology, and anthropology all likely to make significant contributions. PMID:20855628