179 results on '"David J Bennett"'
Search Results
2. Facilitation of sensory transmission to motoneurons during cortical or sensory‐evoked primary afferent depolarization (PAD) in humans
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Krista Metz, Isabel Concha Matos, Yaqing Li, Babak Afsharipour, Christopher K. Thompson, Francesco Negro, Katharina A. Quinlan, David J. Bennett, and Monica A. Gorassini
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Physiology - Published
- 2023
3. GABA facilitates spike propagation through branch points of sensory axons in the spinal cord
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Krishnapriya Hari, Ana M. Lucas-Osma, Krista Metz, Shihao Lin, Noah Pardell, David A. Roszko, Sophie Black, Anna Minarik, Rahul Singla, Marilee J. Stephens, Robert A. Pearce, Karim Fouad, Kelvin E. Jones, Monica A. Gorassini, Keith K. Fenrich, Yaqing Li, and David J. Bennett
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Motor Neurons ,GABAA receptor ,General Neuroscience ,Sensory system ,Optogenetics ,Biology ,Inhibitory postsynaptic potential ,Spinal cord ,Receptors, GABA-A ,Article ,Axons ,medicine.anatomical_structure ,nervous system ,Receptors, GABA-B ,Spinal Cord ,medicine ,GABAergic ,Humans ,Axon ,Receptor ,Neuroscience ,gamma-Aminobutyric Acid - Abstract
Movement and posture depend on sensory feedback that is regulated by specialized GABAergic neurons (GAD2+) that form axo-axonic contacts onto myelinated proprioceptive sensory axons and are thought to be inhibitory. However, we report here that activating GAD2+ neurons, directly with optogenetics or indirectly by cutaneous stimulation, facilitates sensory feedback to motoneurons in awake rodents and humans. GABAA receptors and GAD2+ innervation at or near nodes of Ranvier of sensory axons cause this facilitation, preventing spike propagation failure at the many axon branch points, which is otherwise common without GABA. In contrast, GABAA receptors are generally lacking from axon terminals (unlike GABAB) and do not presynaptically inhibit transmitter release onto motoneurons. GABAergic innervation near nodes and branch points allows individual branches to function autonomously, with GAD2+ neurons regulating which branches conduct, adding a computational layer to the neuronal networks generating movement and likely generalizing to other CNS axons.
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- 2022
4. General Access to Cubanes as Benzene Bioisosteres
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Mario P. Wiesenfeldt, James A. Rossi-Ashton, Ian B. Perry, Johannes Diesel, Olivia L. Garry, Florian Bartels, Susannah C. Coote, Xiaoshen Ma, Charles S. Yeung, David J. Bennett, and David W. C. MacMillan
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Multidisciplinary - Published
- 2023
5. Green operations strategy of a luxury car manufacturer.
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Breno Nunes, David J. Bennett, and Duncan Shaw
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- 2016
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6. Ambiguity, managerial ability, and growth options
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Raymond H.Y. So, Tarik Driouchi, Zhuo Lyu, David J. Bennett, and Mingyu Chen
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Value (ethics) ,Microeconomics ,Identification (information) ,Management of Technology and Innovation ,Strategy and Management ,media_common.quotation_subject ,Perspective (graphical) ,Economics ,Ambiguity ,Negative association ,Endogeneity ,General Business, Management and Accounting ,media_common - Abstract
This paper studies the role of ambiguity and managerial ability in firm growth options from the perspective of behavioural theory. We argue that managerial ability increases both the identification and exploitation of growth options opportunities, but ambiguity reduces strategic growth options value as a result of information incompleteness and non-Bayesian behaviour. Using a dataset of all US-listed firms, we test the joint effects of ambiguity and managerial ability on growth options value after controlling for standard determinants and endogeneity. The results indicate that ambiguity has a negative effect on growth options value, while ability has a positive effect. We also find that the negative association between ambiguity and growth options is less pronounced with higher managerial ability. These findings underscore the importance of firm heterogeneity in the identification, exercise, and management of strategic and innovative real options opportunities. The paper's contribution provides relevant management insights into the behavioural antecedents of real options at the firm level as well as highlights that managerial and behavioural characteristics are important determinants of growth options value.
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- 2022
7. Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons
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Shihao Lin, Krishnapriya Hari, Ana M. Lucas-Osma, Sophie Black, Aysan Khatmi, Karim Fouad, Monica A. Gorassini, Yaqing Li, Keith K. Fenrich, and David J. Bennett
- Abstract
When a muscle is stretched it not only responds with a reflex, but the sensory afferent feedback also depolarizes many afferents throughout the spinal cord (termed primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensory-evoked PAD is thought to be caused by a trisynaptic circuit, where sensory input activates first order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these first order neurons is unclear. Here we show that these first order neurons are propriospinal V3 neurons, since they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents (Na PICs) intrinsic to V3 neurons enable them to respond to transient inputs with long-lasting responses, explaining the long time-course of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, explaining the widespread radiation of PAD across the spinal cord. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. Additionally, we find that V3 neurons directly innervate proprioceptive afferents, causing a glutamate receptor mediated PAD (glutamate PAD). Finally, we show that increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD, perhaps contributing to spasms after SCI. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion.
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- 2022
8. Measuring up the World in Size and Distance Perception
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David J. Bennett
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Philosophy ,Logic - Published
- 2022
9. Gaining social values of wireless technology: An interpretive case study in the healthcare institutional context.
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Wenshin Chen and David J. Bennett
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- 2013
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10. Effects of Navigation and Position on Task When Presenting Diagrams.
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David J. Bennett
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- 2002
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11. Managing enterprise resource planning projects.
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Prasanta Kumar Dey, Benjamin Thomas Clegg, and David J. Bennett
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- 2010
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12. A path-dependent contingent-claims approach to capacity investments.
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Tarik Driouchi, David J. Bennett, and Gary Simpson
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- 2010
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13. Playing catch-up with China: challenges and strategies for smaller developing countries.
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Michel J. Leseure, Dinesh Hurreeram, and David J. Bennett
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- 2009
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14. Technology and business integration.
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Prasanta Kumar Dey, William Ho, Pavel Albores, and David J. Bennett
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- 2009
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15. The Precursors and Impacts of BSR on AMT Acquisition and Implementation.
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Azmawani Abd Rahman, Naomi J. Brookes, and David J. Bennett
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- 2009
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16. Bursting interneurons in the deep dorsal horn develop increased excitability and sensitivity to serotonin after chronic spinal injury
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Vicki M. Tysseling, Charles J. Heckman, Theeradej Thaweerattanasinp, Matthew C. Tresch, Derin Birch, M. C. Jiang, and David J. Bennett
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Dorsum ,Serotonin ,Spasm ,N-Methylaspartate ,Physiology ,Action Potentials ,Mice ,Bursting ,Interneurons ,Animals ,Medicine ,Spinal cord injury ,Oxazolidinones ,Spinal Cord Injuries ,Spinal injury ,5-HT receptor ,Motor Neurons ,business.industry ,Horn (anatomy) ,General Neuroscience ,Excitatory Postsynaptic Potentials ,Serotonin 5-HT1 Receptor Agonists ,medicine.disease ,Tryptamines ,Mice, Inbred C57BL ,Posterior Horn Cells ,Disease Models, Animal ,nervous system ,Chronic Disease ,NMDA receptor ,Spinal Nerve Roots ,business ,Neuroscience ,Research Article - Abstract
The loss of descending serotonin (5-HT) to the spinal cord contributes to muscle spasms in chronic spinal cord injury (SCI). Hyperexcitable motoneurons receive long-lasting excitatory postsynaptic potentials (EPSPs), which activate their persistent inward currents to drive muscle spasms. Deep dorsal horn (DDH) neurons with bursting behavior could be involved in triggering the EPSPs due to loss of inhibition in the chronically 5-HT-deprived spinal cord. Previously, in an acutely transected preparation, we found that bursting DDH neurons were affected by administration of the 5-HT(1B/1D) receptor agonist zolmitriptan, which suppressed their bursts, and by N-methyl-d-aspartate (NMDA), which enhanced their bursting behavior. Nonbursting DDH neurons were not influenced by these agents. In the present study, we investigate the firing characteristics of bursting DDH neurons following chronic spinal transection at T10 level in adult mice and examine the effects of replacing lost endogenous 5-HT with zolmitriptan. Terminal experiments using our in vitro preparation of the sacral cord were carried out ~10 wk postransection. Compared with the acute spinal stage of our previous study, DDH neurons in the chronic stage became more responsive to dorsal root stimulation, with burst duration doubling with chronic injury. The suppressive effects of zolmitriptan were stronger overall, but the facilitative effects of NMDA were weaker. In addition, the onset of DDH neuron activity preceded ventral root output and the firing rates of DDH interneurons correlated with the integrated long-lasting ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following SCI and inhibition by 5-HT. NEW & NOTEWORTHY We investigate the firing characteristics of bursting deep dorsal horn (DDH) neurons following chronic spinal transection. DDH neurons in the chronic stage are different from those in the acute stage as noted by their increase in excitability overall and their differing responses serotonin (5-HT) and N-methyl-d-aspartate (NMDA) receptor agonists. Also, there is a strong relationship between DDH neuron activity and ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following chronic spinal cord injury (SCI).
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- 2020
17. Meeting technology needs of enterprises for national competitiveness.
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David J. Bennett and Kirit Vaidya
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- 2005
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18. Kinematic calibration by direct estimation of the Jacobian matrix.
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David J. Bennett, John M. Hollerbach, and Paul D. Henri
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- 1992
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19. Impacts and relationships between three evolving disciplines.
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Anders Drejer, David J. Bennett, and Amrik S. Sohal
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- 2002
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20. Technology transfer to China: a study of strategy in 20 EU industrial companies.
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David J. Bennett, Xiaming Liu, David Parker 0005, Fred Steward, and Kirit Vaidya
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- 2001
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21. 5-HT1Dreceptors inhibit the monosynaptic stretch reflex by modulating C-fiber activity
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Ana M. Lucas-Osma, Yaqing Li, Marilee J. Stephens, Sophie Black, Andrew H. Ahn, Keith K. Fenrich, Katie Murray, David J. Bennett, Karim Fouad, Charles J. Heckman, and Shihao Lin
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Reflex, Stretch ,Physiology ,Serotonin 5-HT1 Receptor Antagonists ,medicine ,Animals ,Spasticity ,Stretch reflex ,Fiber ,Receptor ,Spinal cord injury ,Spinal Cord Injuries ,Serotonin Plasma Membrane Transport Proteins ,Nerve Fibers, Unmyelinated ,Chemistry ,General Neuroscience ,Serotonin 5-HT1 Receptor Agonists ,medicine.disease ,Afferent transmission ,Rats ,Nociception ,medicine.anatomical_structure ,Receptor, Serotonin, 5-HT1D ,Female ,Serotonin ,medicine.symptom ,Neuroscience ,Research Article - Abstract
The monosynaptic stretch reflex (MSR) plays an important role in feedback control of movement and posture but can also lead to unstable oscillations associated with tremor and clonus, especially when increased with spinal cord injury (SCI). To control the MSR and clonus after SCI, we examined how serotonin regulates the MSR in the sacrocaudal spinal cord of rats with and without a chronic spinal transection. In chronic spinal rats, numerous 5-HT receptor agonists, including zolmitriptan, methylergonovine, and 5-HT, inhibited the MSR with a potency highly correlated to their binding affinity to 5-HT1Dreceptors and not other 5-HT receptors. Selective 5-HT1Dreceptor antagonists blocked this agonist-induced inhibition, although antagonists alone had no action, indicating a lack of endogenous or constitutive receptor activity. In normal uninjured rats, the MSR was likewise inhibited by 5-HT, but at much higher doses, indicating a supersensitivity after SCI. This supersensitivity resulted from the loss of the serotonin transporter SERT with spinal transection, because normal and injured rats were equally sensitive to 5-HT after SERT was blocked or to agonists not transported by SERT (zolmitriptan). Immunolabeling revealed that the 5-HT1Dreceptor was confined to superficial lamina of the dorsal horn, colocalized with CGRP-positive C-fibers, and eliminated by dorsal rhizotomy. 5-HT1Dreceptor labeling was not found on large proprioceptive afferents or α-motoneurons of the MSR. Thus serotonergic inhibition of the MSR acts indirectly by modulating C-fiber activity, opening up new possibilities for modulating reflex function and clonus via pain-related pathways.NEW & NOTEWORTHY Brain stem-derived serotonin potently inhibits afferent transmission in the monosynaptic stretch reflex. We show that serotonin produces this inhibition exclusively via 5-HT1Dreceptors, and yet these receptors are paradoxically mostly confined to C-fibers. This suggests that serotonin acts by gating of C-fiber activity, which in turn modulates afferent transmission to motoneurons. We also show that the classic supersensitivity to 5-HT after spinal cord injury results from a loss of SERT, and not 5-HT1Dreceptor plasticity.
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- 2019
22. Extrasynaptic α5GABAA receptors on proprioceptive afferents produce a tonic depolarization that modulates sodium channel function in the rat spinal cord
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Ana M. Lucas-Osma, Rahul Singla, David J. Bennett, Sophie Black, Yaqing Li, Keith K. Fenrich, Shihao Lin, and Karim Fouad
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0301 basic medicine ,Proprioception ,Physiology ,GABAA receptor ,Chemistry ,General Neuroscience ,Sodium channel ,Depolarization ,Spinal cord ,Tonic (physiology) ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,GABAergic ,Receptor ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Activation of GABAA receptors on sensory axons produces a primary afferent depolarization (PAD) that modulates sensory transmission in the spinal cord. While axoaxonic synaptic contacts of GABAergic interneurons onto afferent terminals have been extensively studied, less is known about the function of extrasynaptic GABA receptors on afferents. Thus, we examined extrasynaptic α5GABAA receptors on low-threshold proprioceptive (group Ia) and cutaneous afferents. Afferents were impaled with intracellular electrodes and filled with neurobiotin in the sacrocaudal spinal cord of rats. Confocal microscopy was used to reconstruct the afferents and locate immunolabelled α5GABAA receptors. In all afferents α5GABAA receptors were found throughout the extensive central axon arbors. They were most densely located at branch points near sodium channel nodes, including in the dorsal horn. Unexpectedly, proprioceptive afferent terminals on motoneurons had a relative lack of α5GABAA receptors. When recording intracellularly from these afferents, blocking α5GABAA receptors (with L655708, gabazine, or bicuculline) hyperpolarized the afferents, as did blocking neuronal activity with tetrodotoxin, indicating a tonic GABA tone and tonic PAD. This tonic PAD was increased by repeatedly stimulating the dorsal root at low rates and remained elevated for many seconds after the stimulation. It is puzzling that tonic PAD arises from α5GABAA receptors located far from the afferent terminal where they can have relatively little effect on terminal presynaptic inhibition. However, consistent with the nodal location of α5GABAA receptors, we find tonic PAD helps produce sodium spikes that propagate antidromically out the dorsal roots, and we suggest that it may well be involved in assisting spike transmission in general. NEW & NOTEWORTHY GABAergic neurons are well known to form synaptic contacts on proprioceptive afferent terminals innervating motoneurons and to cause presynaptic inhibition. However, the particular GABA receptors involved are unknown. Here, we examined the distribution of extrasynaptic α5GABAA receptors on proprioceptive Ia afferents. Unexpectedly, these receptors were found preferentially near nodal sodium channels throughout the afferent and were largely absent from afferent terminals. These receptors produced a tonic afferent depolarization that modulated sodium spikes, consistent with their location.
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- 2018
23. Rehabilitative training improves skilled forelimb motor function after cervical unilateral contusion spinal cord injury in rats
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Ana M, Lucas-Osma, Emma K A, Schmidt, Romana, Vavrek, David J, Bennett, Karim, Fouad, and Keith K, Fenrich
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Disease Models, Animal ,Behavioral Neuroscience ,Behavior, Animal ,Motor Skills ,Contusions ,Physical Conditioning, Animal ,Forelimb ,Neurological Rehabilitation ,Animals ,Cervical Cord ,Spinal Cord Injuries ,Exercise Therapy ,Rats - Abstract
Animal models of cervical spinal cord injury (SCI) have frequently utilized partial transection injuries to evaluate plasticity promoting treatments such as rehabilitation training of skilled reaching and grasping tasks. Though highly useful for studying the effects of cutting specific spinal tracts that are important for skilled forelimb motor function, cervical partial-transection SCI-models underappreciate the extensive spread of most human SCIs, thus offering poor predictability for the clinical setting. Conversely, moderate cervical contusion SCI models targeting the spinal tracts important for skilled reaching and grasping can better replicate the increased size of most human SCIs and are often considered more clinically relevant. However, it is unknown whether animals with moderate cervical contusion SCIs that damage key spinal motor tracts can train in skilled reaching and grasping tasks. In this study, we quantify the impact of injury size and distribution on recovery in a skilled motor task called the single pellet reaching, grasping and retrieval (SPRGR) task in rats with cervical unilateral contusion injuries (UCs), and compare to rats with a partial transection SCIs (i.e., dorsolateral quadrant transection; DLQ). We found that UCs damage key tracts important for performing skilled motor tasks, similar to DLQs, but UCs also produce more extensive grey matter damage and more ventral white matter damage than DLQs. We also compared forelimb functionality at 1, 3, and 5 weeks of rehabilitative motor training between trained and untrained rats and found a more severe drop in SPRGR performance than in DLQ SCIs. Nevertheless, despite more severe injuries and initially low SPRGR performance, rehabilitative training for contusion animals resulted in significant improvements in SPRGR performance and proportionally more recovery than DLQ rats. Our findings show that rehabilitative motor training can facilitate considerable amounts of motor recovery despite extensive spinal cord damage, especially grey matter damage, thus supporting the use of contusion or compression SCI models and showing that ventral grey and white matter damage are not necessarily detrimental to recovery after training.
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- 2022
24. Estimation of self-sustained activity produced by persistent inward currents using firing rate profiles of multiple motor units in humans
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Jennifer Duchcherer, Katharina A. Quinlan, Nagib Manzur, Keith F Fenrich, Christopher K. Thompson, Babak Afsharipour, Monica A. Gorassini, David J. Bennett, and Francesco Negro
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Adult ,Male ,Recruitment, Neurophysiological ,Persistent inward currents ,Tibialis anterior ,Physiology ,High-density surface EMG ,Electromyography ,Sodium current ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,medicine ,Humans ,Muscle, Skeletal ,030304 developmental biology ,Physics ,Motor Neurons ,0303 health sciences ,medicine.diagnostic_test ,General Neuroscience ,musculoskeletal, neural, and ocular physiology ,Inward calcium ,Depolarization ,Middle Aged ,Synaptic Potentials ,Motoneurons ,nervous system ,Female ,Recruitment threshold ,Neuroscience ,030217 neurology & neurosurgery ,Research Article - Abstract
Persistent inward calcium and sodium currents (I(P)) activated during motoneuron recruitment help synaptic inputs maintain self-sustained firing until derecruitment. Here, we estimate the contribution of the I(P) to self-sustained firing in human motoneurons of varying recruitment threshold by measuring the difference in synaptic input needed to maintain minimal firing once the I(P) is fully activated compared with the larger synaptic input required to initiate firing before full I(P) activation. Synaptic input to ≈20 dorsiflexor motoneurons simultaneously recorded during ramp contractions was estimated from firing profiles of motor units decomposed from high-density surface electromyography (EMG). To avoid errors introduced when using high-threshold units firing in their nonlinear range, we developed methods where the lowest threshold units firing linearly with force were used to construct a composite (control) unit firing rate profile to estimate synaptic input to higher threshold (test) units. The difference in the composite firing rate (synaptic input) at the time of test unit recruitment and derecruitment (ΔF = F(recruit) − F(derecruit)) was used to measure I(P) amplitude that sustained firing. Test units with recruitment thresholds 1–30% of maximum had similar ΔF values, which likely included both slow and fast motor units activated by small and large motoneurons, respectively. This suggests that the portion of the I(P) that sustains firing is similar across a wide range of motoneuron sizes. NEW & NOTEWORTHY A new method of estimating synaptic drive to multiple, simultaneously recorded motor units provides evidence that the portion of the depolarizing drive from persistent inward currents that contributes to self-sustained firing is similar across motoneurons of different sizes.
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- 2020
25. Branching points of primary afferent fibers are vital for the modulation of fiber excitability by epidural DC polarization and by GABA in the rat spinal cord
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Ingela Hammar, Yaqing Li, Krishnapriya Hari, David J. Bennett, Ana M. Lucas-Osma, Keith K. Fenrich, and Elzbieta Jankowska
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Agonist ,Epidural Space ,Male ,Physiology ,Myelinated nerve fiber ,medicine.drug_class ,Sensory system ,Stimulation ,Nerve Fibers, Myelinated ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,medicine ,Animals ,Anesthesia ,GABA-A Receptor Agonists ,GABA-A Receptor Antagonists ,Neurons, Afferent ,Peripheral Nerves ,gamma-Aminobutyric Acid ,Neuronal Plasticity ,Chemistry ,GABAA receptor ,General Neuroscience ,Bicuculline ,Spinal cord ,Electric Stimulation ,Electrophysiological Phenomena ,Rats ,medicine.anatomical_structure ,Muscimol ,Spinal Cord ,Biophysics ,Female ,medicine.drug ,Research Article - Abstract
The aim of the study was to examine whether the sustained increases in the excitability of afferent fibers traversing the dorsal columns evoked by their polarization depend on the branching points of these fibers. To this end, the effects of epidural polarization were compared in four spinal regions in deeply anesthetized rats; two with the densest collateralization of muscle afferent fibers (above motor nuclei and Clarke’s column) and two where the collateralization is more sparse (rostral and caudal to motor nuclei, respectively. The degree of collateralization in different segments was reconstructed in retrogradely labeled afferent fibers in the rat. Nerve volleys evoked in peripheral nerves by electrical stimulation of the dorsal columns within these regions were used as a measure of the excitability of the stimulated fibers. Potent increases in the excitability were evoked by polarization above motor nuclei and Clarke’s column, both during constant direct current (DC) polarization (1 µA for 1 min) and for at least 30 min following DC polarization. Smaller excitability increases occurred during the polarization within other regions and were thereafter either absent or rapidly declined after its termination. The postpolarization increases in excitability were counteracted by the GABA(A) receptor antagonist bicuculline and the (α5)GABA(A) extrasynaptic receptor antagonist L655708 and enhanced by the GABA(A) receptor agonist muscimol and by ionophoretically applied GABA. As extrasynaptic (α5)GABA(A) receptors have been found close to Na channels within branching points, these results are consistent with the involvement of branching points in the induction of the sustained postpolarization increases in fiber excitability. NEW & NOTEWORTHY Polarization of sensory fibers traversing dorsal columns of the spinal cord may considerably increase the excitability of these fibers. We show that this involves the effects of current at branching points of afferent fibers and depends on extrasynaptic effects of GABA. These results contribute to our understanding of the mechanism underlying plasticity of activation of nerve fibers and may be used to increase the effectiveness of epidural stimulation in humans and recovery of spinal functions.
- Published
- 2020
26. Self-directed rehabilitation training intensity thresholds for efficient recovery of skilled forelimb function in rats with cervical spinal cord injury
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Pamela J. F. Raposo, Karim Fouad, Abel Torres-Espín, David J. Bennett, Keith K. Fenrich, Romana Vavrek, John E. Misiaszek, and Ben W. Hallworth
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0301 basic medicine ,medicine.medical_specialty ,media_common.quotation_subject ,medicine.medical_treatment ,education ,Task (project management) ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Developmental Neuroscience ,Neuroplasticity ,Forelimb ,medicine ,Animals ,Function (engineering) ,Spinal cord injury ,Spinal Cord Injuries ,media_common ,Rehabilitation ,business.industry ,Motor control ,Cervical Cord ,Recovery of Function ,medicine.disease ,Rats ,Self Care ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Motor Skills ,Rats, Inbred Lew ,Corticospinal tract ,Female ,business ,030217 neurology & neurosurgery - Abstract
Task specific rehabilitation training is commonly used to treat motor dysfunction after neurological injures such as spinal cord injury (SCI), yet the use of task specific training in preclinical animal studies of SCI is not common. This is due in part to the difficulty in training animals to perform specific motor tasks, but also due to the lack of knowledge about optimal rehabilitation training parameters to maximize recovery. The single pellet reaching, grasping and retrieval (SPRGR) task (a.k.a. single pellet reaching task or Whishaw task) is a skilled forelimb motor task used to provide rehabilitation training and test motor recovery in rodents with cervical SCI. However, the relationships between the amount, duration, intensity, and timing of training remain poorly understood. In this study, using automated robots that allow rats with cervical SCI ad libitum access to self-directed SPRGR rehabilitation training, we show clear relationships between the total amount of rehabilitation training, the intensity of training (i.e., number of attempts/h), and performance in the task. Specifically, we found that rats naturally segregate into High and Low performance groups based on training strategy and performance in the task. Analysis of the different training strategies showed that more training (i.e., increased number of attempts in the SPRGR task throughout rehabilitation training) at higher intensities (i.e., number of attempts per hour) increased performance in the task, and that improved performance in the SPRGR task was linked to differences in corticospinal tract axon collateral densities in the injured spinal cords. Importantly, however, our data also indicate that rehabilitation training becomes progressively less efficient (i.e., less recovery for each attempt) as both the amount and intensity of rehabilitation training increases. Finally, we found that Low performing animals could increase their training intensity and transition to High performing animals in chronic SCI. These results highlight the rehabilitation training strategies that are most effective to regain skilled forelimb motor function after SCI, which will facilitate pre-clinical rehabilitation studies using animal models and could be beneficial in the development of more efficient clinical rehabilitation training strategies.
- Published
- 2020
27. Autonomous calibration of single-loop closed kinematic chains formed by manipulators with passive endpoint constraints.
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David J. Bennett and John M. Hollerbach
- Published
- 1991
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28. Autonomous Robot Calibration for Hand-Eye Coordination.
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David J. Bennett, Davi Geiger, and John M. Hollerbach
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- 1991
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29. Eliciting inflammation enables successful rehabilitative training in chronic spinal cord injury
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Pamela J. F. Raposo, Romana Vavrek, David J. Bennett, Karim Fouad, Aleksandra Krajacic, Ana M. Lucas-Osma, Emma K. A. Schmidt, Juan Forero, Phillip G. Popovich, Abel Torres-Espín, and Keith K. Fenrich
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Lipopolysaccharides ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Pyramidal Tracts ,Inflammation ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Forelimb ,medicine ,Animals ,Spinal cord injury ,Spinal Cord Injuries ,Neuroinflammation ,Neuronal Plasticity ,Rehabilitation ,business.industry ,Cervical Cord ,Recovery of Function ,Myelitis ,medicine.disease ,Spinal cord ,Polytrauma ,Nerve Regeneration ,Rats ,3. Good health ,Electrophysiology ,030104 developmental biology ,medicine.anatomical_structure ,Spinal Cord ,Rats, Inbred Lew ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Rehabilitative training is one of the most successful therapies to promote motor recovery after spinal cord injury, especially when applied early after injury. Polytrauma and management of other medical complications in the acute post-injury setting often preclude or complicate early rehabilitation. Therefore, interventions that reopen a window of opportunity for effective motor training after chronic injury would have significant therapeutic value. Here, we tested whether this could be achieved in rats with chronic (8 weeks) dorsolateral quadrant sections of the cervical spinal cord (C4) by inducing mild neuroinflammation. We found that systemic injection of a low dose of lipopolysaccharide improved the efficacy of rehabilitative training on forelimb function, as assessed using a single pellet reaching and grasping task. This enhanced recovery was found to be dependent on the training intensity, where a high-intensity paradigm induced the biggest improvements. Importantly, in contrast to training alone, the combination of systemic lipopolysaccharide and high-intensity training restored original function (reparative plasticity) rather than enhancing new motor strategies (compensatory plasticity). Accordingly, electrophysiological and tract-tracing studies demonstrated a recovery in the cortical drive to the affected forelimb muscles and a restructuration of the corticospinal innervation of the cervical spinal cord. Thus, we propose that techniques that can elicit mild neuroinflammation may be used to enhance the efficacy of rehabilitative training after chronic spinal cord injury.
- Published
- 2018
30. The Social Values of Wireless Technology in the Institutional Context.
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Wenshin Chen and David J. Bennett
- Published
- 2010
31. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury
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Marilee J. Stephens, Leo Sanelli, Keith K. Fenrich, Mischa V Bandet, Ana M. Lucas-Osma, Yaqing Li, Romana Vavrek, Antonio Fabio Di Narzo, Ian R. Winship, Sophie Black, Stella Dracheva, David J. Bennett, and Karim Fouad
- Subjects
0301 basic medicine ,capillary ,Norepinephrine ,0302 clinical medicine ,pericyte ,AADC ,Premovement neuronal activity ,Hypoxia ,Spinal cord injury ,Injections, Spinal ,Microscopy, Confocal ,Chemistry ,General Medicine ,Tryptamines ,locomotion ,medicine.anatomical_structure ,Aromatic-L-Amino-Acid Decarboxylases ,Anesthesia ,Receptor, Serotonin, 5-HT1B ,Trace amines ,motoneurons ,medicine.symptom ,Serotonin ,medicine.medical_specialty ,neurovascular coupling ,Central nervous system ,Tyramine ,ischemia ,Serotonin 5-HT1 Receptor Antagonists ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Receptors, Adrenergic, alpha-2 ,Internal medicine ,medicine ,Animals ,Biogenic Monoamines ,Microscopy, Interference ,RNA, Messenger ,Spinal Cord Injuries ,Oxygen Inhalation Therapy ,medicine.disease ,Spinal cord ,spinal cord injury ,5-HT1B receptor ,Capillaries ,Rats ,Oxygen ,030104 developmental biology ,Monoamine neurotransmitter ,Endocrinology ,Vasoconstriction ,Neuron ,Pericytes ,Transcriptome ,Receptors, Serotonin, 5-HT1 ,030217 neurology & neurosurgery - Abstract
Blood vessels in the central nervous system (CNS) are controlled by neuronal activity. For example, widespread vessel constriction (vessel tone) is induced by brainstem neurons that release the monoamines serotonin and noradrenaline, and local vessel dilation is induced by glutamatergic neuron activity. Here we examined how vessel tone adapts to the loss of neuron-derived monoamines after spinal cord injury (SCI) in rats. We find that, months after the imposition of SCI, the spinal cord below the site of injury is in a chronic state of hypoxia owing to paradoxical excess activity of monoamine receptors (5-HT1) on pericytes, despite the absence of monoamines. This monoamine-receptor activity causes pericytes to locally constrict capillaries, which reduces blood flow to ischemic levels. Receptor activation in the absence of monoamines results from the production of trace amines (such as tryptamine) by pericytes that ectopically express the enzyme aromatic L-amino acid decarboxylase (AADC), which synthesizes trace amines directly from dietary amino acids (such as tryptophan). Inhibition of monoamine receptors or of AADC, or even an increase in inhaled oxygen, produces substantial relief from hypoxia and improves motoneuron and locomotor function after SCI.
- Published
- 2017
32. A Selective Synthesis of 2,2-Difluorobicyclo[1.1.1]pentane Analogues: 'BCP-F
- Author
-
Xiaoshen, Ma, David L, Sloman, Yongxin, Han, and David J, Bennett
- Abstract
The bicyclo[1.1.1]pentane (BCP) motif has been utilized as bioisosteres in drug candidates to replace phenyl
- Published
- 2019
33. Motor axon excitability measures in the rat tail are the same awake or anaesthetized using sodium pentobarbital
- Author
-
David J. Bennett and Kelvin E. Jones
- Subjects
0303 health sciences ,Adult female ,business.industry ,Stimulation ,Sodium pentobarbital ,Rat tail ,Xylazine ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Anesthesia ,Medicine ,Ketamine ,Axon ,business ,Sacral spinal cord ,030217 neurology & neurosurgery ,030304 developmental biology ,medicine.drug - Abstract
BackgroundNerve excitability tests in sciatic motor axons are sensitive to anaesthetic choice. Results using ketamine/xylazine (KX) are different from those using sodium pentobarbital (SP). It is not clear which results are most similar to the awake condition, though results using SP appear more similar to human results.MethodsNerve excitability in tail motor axons was tested in 8 adult female rats with a chronic sacral spinal cord injury. These animals have no behavioural response to electrical stimulation of the tail and were tested awake and then anaesthetized using SP.ResultsThe nerve excitability test results in the awake condition were indistinguishable from the results when the same rats were anaesthetized with sodium pentobarbital. Summary plots of the test results overlap within the boundaries of the standard error and paired t-tests on the 42 discrete measures generated by nerve excitability testing yielded no significant differences (after Bonferroni correction for multiple comparisons).ConclusionsNerve excitability test results in rat motor axons are the same whether the animals are awake or anesthetized using sodium pentobarbital.
- Published
- 2019
34. V3 neurons regulate sensory transmission as well as locomotion
- Author
-
Karim Fouad, Ana M. Lucas-Osma, Krishnapriya Hari, Shihao Lin, Keith K. Fenrich, Yaqing Li, and David J. Bennett
- Subjects
0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Sensory transmission ,Genetics ,Biology ,Molecular Biology ,Biochemistry ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2019
35. Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury
- Author
-
Rahul Singla, Ana M. Lucas-Osma, Yaqing Li, Krishnapriya Hari, David J. Bennett, Marilee J. Stephens, Keith K. Fenrich, Charles J. Heckman, Karim Fouad, Ying Zhang, and Shihao Lin
- Subjects
Male ,Physiology ,Optogenetics ,Mice ,Interneurons ,medicine ,Animals ,Spasticity ,Muscle, Skeletal ,Spinal cord injury ,Spinal Cord Injuries ,Motor Neurons ,business.industry ,General Neuroscience ,Extremities ,medicine.disease ,Spinal Nerves ,nervous system ,Muscle Spasticity ,Spinal transection ,Excitatory postsynaptic potential ,Central Pattern Generators ,Female ,medicine.symptom ,business ,Neuroscience ,muscle spasm ,Muscle Contraction ,Research Article - Abstract
Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.
- Published
- 2019
36. Destabilizing Effects of Terrorism on Party System Stability
- Author
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Joseph W. Robbins, Lance Y. Hunter, and David J. Bennett
- Subjects
Government ,Sociology and Political Science ,media_common.quotation_subject ,05 social sciences ,System stability ,050601 international relations ,Democracy ,0506 political science ,Variety (cybernetics) ,Democratic consolidation ,Politics ,Law ,Political economy ,Political science ,Political Science and International Relations ,Terrorism ,050602 political science & public administration ,Safety, Risk, Reliability and Quality ,Safety Research ,Socioeconomic status ,media_common - Abstract
In democracies with stable party systems, voters can more easily trace policy decisions from parties and representatives within the government to specific policy outcomes. Consequently, party system stability (PSS) has been reportedly linked to a variety of factors including economic conditions, democratic performance, political institutions, and socioeconomic cleavages. While informative, these lessons offer precious little insight into other factors that can destabilize a party system. In this work, we surmise that terrorist attacks have important implications for two commonly used measures of PSS. The results of a pooled, cross-sectional time series analysis confirm our hypothesis: deadly attacks proximate to elections destabilize party systems, even when controlling for multiple standard controls. In addition, the level of democratic consolidation within states also influences the degree that fatal terrorist attacks affect party system stability. These findings are based on terrorism data coll...
- Published
- 2016
37. Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot
- Author
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Abel Torres-Espín, Zacincte May, David J. Bennett, Karim Fouad, Keith K. Fenrich, and Juan Forero
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,education ,Article ,Task (project management) ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Physical medicine and rehabilitation ,Physical Conditioning, Animal ,Forelimb ,Single pellet ,Neuroplasticity ,medicine ,Animals ,Spinal cord injury ,Spinal Cord Injuries ,Motor skill ,Neuronal Plasticity ,Rehabilitation ,Foot ,business.industry ,Training (meteorology) ,Cervical Cord ,Recovery of Function ,Robotics ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Food ,Motor Skills ,Rats, Inbred Lew ,Female ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24 h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury.
- Published
- 2016
38. The Role of Spatial Appearances in Achieving Spatial-Geometric Perceptual Constancy
- Author
-
David J. Bennett
- Subjects
Philosophy of mind ,media_common.quotation_subject ,05 social sciences ,06 humanities and the arts ,0603 philosophy, ethics and religion ,050105 experimental psychology ,Visual field ,Philosophy ,Subjective constancy ,Empirical research ,Analytic philosophy ,Order (business) ,Perception ,060302 philosophy ,0501 psychology and cognitive sciences ,Psychology ,Empirical psychology ,Cognitive psychology ,media_common - Abstract
Long tradition in philosophy and in empirical psychology has it that the perceptual recovery of enduring objective size and shape proceeds through initial spatial appearance experiences—like the sensed changing visual field size of a receding car, or the shifting shape appearance of a coin as it rotates in depth. The present paper carefully frames and then critically examines such proposals. It turns out that these are contingent, empirical matters, requiring close examination of relevant research in perception science in order to decide. The paper concludes with extended discussions of the empirical study of the perception of slant, size, and shape.
- Published
- 2016
39. Extrasynaptic α
- Author
-
Ana M, Lucas-Osma, Yaqing, Li, Shihao, Lin, Sophie, Black, Rahul, Singla, Karim, Fouad, Keith K, Fenrich, and David J, Bennett
- Subjects
Neural Inhibition ,Proprioception ,Receptors, GABA-A ,Sodium Channels ,Membrane Potentials ,Rats ,Rats, Sprague-Dawley ,nervous system ,Spinal Cord ,Synapses ,Animals ,Female ,GABA-A Receptor Antagonists ,Neurons, Afferent ,Research Article - Abstract
Activation of GABA(A) receptors on sensory axons produces a primary afferent depolarization (PAD) that modulates sensory transmission in the spinal cord. While axoaxonic synaptic contacts of GABAergic interneurons onto afferent terminals have been extensively studied, less is known about the function of extrasynaptic GABA receptors on afferents. Thus, we examined extrasynaptic α(5)GABA(A) receptors on low-threshold proprioceptive (group Ia) and cutaneous afferents. Afferents were impaled with intracellular electrodes and filled with neurobiotin in the sacrocaudal spinal cord of rats. Confocal microscopy was used to reconstruct the afferents and locate immunolabelled α(5)GABA(A) receptors. In all afferents α(5)GABA(A) receptors were found throughout the extensive central axon arbors. They were most densely located at branch points near sodium channel nodes, including in the dorsal horn. Unexpectedly, proprioceptive afferent terminals on motoneurons had a relative lack of α(5)GABA(A) receptors. When recording intracellularly from these afferents, blocking α(5)GABA(A) receptors (with L655708, gabazine, or bicuculline) hyperpolarized the afferents, as did blocking neuronal activity with tetrodotoxin, indicating a tonic GABA tone and tonic PAD. This tonic PAD was increased by repeatedly stimulating the dorsal root at low rates and remained elevated for many seconds after the stimulation. It is puzzling that tonic PAD arises from α(5)GABA(A) receptors located far from the afferent terminal where they can have relatively little effect on terminal presynaptic inhibition. However, consistent with the nodal location of α(5)GABA(A) receptors, we find tonic PAD helps produce sodium spikes that propagate antidromically out the dorsal roots, and we suggest that it may well be involved in assisting spike transmission in general. NEW & NOTEWORTHY GABAergic neurons are well known to form synaptic contacts on proprioceptive afferent terminals innervating motoneurons and to cause presynaptic inhibition. However, the particular GABA receptors involved are unknown. Here, we examined the distribution of extrasynaptic α(5)GABA(A) receptors on proprioceptive Ia afferents. Unexpectedly, these receptors were found preferentially near nodal sodium channels throughout the afferent and were largely absent from afferent terminals. These receptors produced a tonic afferent depolarization that modulated sodium spikes, consistent with their location.
- Published
- 2018
40. A Lifetime’s Fun and Interest with Teaching and Allied Matters
- Author
-
Richard C. Jennings, David J. Bennett, and Ian Harvey
- Subjects
Pedagogy ,Psychology ,Social psychology - Published
- 2017
41. Researching My Career
- Author
-
David J. Bennett, Lori Conlan, and Richard C. Jennings
- Subjects
Medical education ,Pedagogy ,Career education ,Sociology - Published
- 2017
42. Opportunities for Entrepreneurial Scientists and Engineers in the Post-Genomic Era
- Author
-
Darrin M. Disley, David J. Bennett, and Richard C. Jennings
- Published
- 2017
43. From Lab Bench to Boardroom
- Author
-
Richard C. Jennings, Robert Stephen, and David J. Bennett
- Subjects
Engineering ,business.industry ,Engineering ethics ,business - Published
- 2017
44. What to Do When You Don’t Know What You’re Doing; Or, My First Twenty-Five Years in Science Communication
- Author
-
David J. Bennett, John Durant, and Richard C. Jennings
- Subjects
Science communication ,Library science ,Sociology - Published
- 2017
45. Environmental Policy, Politics and Science – Not Always an Easy Ride
- Author
-
Julie Hill, David J. Bennett, and Richard C. Jennings
- Subjects
Politics ,Political science ,Environmental policy ,Public administration - Published
- 2017
46. From Rock Pools to Whitehall
- Author
-
David J. Bennett, Miles Parker, and Richard C. Jennings
- Subjects
geography ,geography.geographical_feature_category ,Geochemistry ,Tide pool - Published
- 2017
47. Doctoral Graduates in Policy and Advocacy
- Author
-
Adam Wright, David J. Bennett, and Richard C. Jennings
- Subjects
Political science ,Public administration - Published
- 2017
48. In Search of the Ethical Path
- Author
-
Stuart Parkinson, Richard C. Jennings, and David J. Bennett
- Subjects
Mathematical optimization ,Computer science ,Path (graph theory) - Published
- 2017
49. Reflections of a Thinking Pinball
- Author
-
David J. Bennett, Peter Evans, and Richard C. Jennings
- Subjects
business.industry ,Political science ,Public relations ,business - Published
- 2017
50. A Career in Science Radio and Podcasting
- Author
-
Kat Arney, David J. Bennett, Chris Smith, and Richard C. Jennings
- Subjects
Pedagogy ,Library science ,Sociology - Published
- 2017
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