scholarly journals Oxaliplatin neurotoxicity of sensory transduction in rat proprioceptors

2011 ◽  
Vol 106 (2) ◽  
pp. 704-709 ◽  
Author(s):  
Katie L. Bullinger ◽  
Paul Nardelli ◽  
Qingbo Wang ◽  
Mark M. Rich ◽  
Timothy C. Cope
Keyword(s):  
Action Potentials ◽  
Muscle Length ◽  
Sensory Transduction ◽  
Muscle Stretch ◽  
Functional Deficits ◽  
Oxaliplatin Treatment ◽  
Sensory Encoding ◽  
Dying Back ◽  
Striking Contrast

Neurotoxic effects of oxaliplatin chemotherapy, including proprioceptive impairments, are debilitating and dose limiting. Here, we sought to determine whether oxaliplatin interrupts normal proprioceptive feedback by impairing sensory transduction of muscle length and force by neurons that are not damaged by dying-back neuropathy. Oxaliplatin was administered over 4 wk to rats in doses that produced systemic changes, e.g., decreased platelets and stunted weight gain, but no significant abnormality in the terminal ends of primary muscle spindle sensory neurons. The absence of neuropathy enabled the determination of whether oxaliplatin caused functional deficits in sensory encoding without the confounding issue of axon death. Rats were anesthetized, and action potentials encoding muscle stretch and contraction were recorded intra-axonally from dorsal roots. In striking contrast with normal proprioceptors, those from oxaliplatin-treated rats typically failed to sustain firing during static muscle stretch. The ability of spindle afferents to sustain and centrally conduct trains of action potentials in response to rapidly repeated transient stimuli, i.e., vibration, demonstrated functional competence of the parent axons. These data provide the first evidence that oxaliplatin causes persistent and selective deficits in sensory transduction that are not due to axon degeneration. Our findings raise the possibility that even those axons that do not degenerate after oxaliplatin treatment may have functional deficits that worsen outcome.

Responses of cortical neurons (areas 3a and 4) to ramp stretch of hindlimb muscles in the baboon

1976 ◽  
Vol 39 (3) ◽  
pp. 484-500 ◽  
Author(s):  
J. Hore ◽  
J. B. Preston ◽  
P. D. Cheney
Keyword(s):  
Cortical Neurons ◽  
Muscle Length ◽  
Muscle Afferents ◽  
Muscle Stretch ◽  
Hindlimb Muscles ◽  
Group I ◽  
Hindlimb Muscle ◽  
Area 3A ◽  
Group Ii Muscle Afferents ◽  
Group Ii

1. A study was made of the response of single cortical units in areas 3a and 4 to electrical stimulation of hindlimb muscle nerves and to ramp stretch of hindlimb muscles in baboons anesthetized with chloralose.2. Stimulation of hindlimb muscle nerves revealed a group I projection primarily to area 3a but with some input into adjacent area. 4. A major group II projection was found in area 4 adjacent to area 3a. A small number of area 3a neurons receive convergence from both group I and group II muscle afferents.3a. On the basis of their response pattern to ramp stretch, units were classified into one of six categories and their cytoarchitectonic location was determined. Units in area 3a had hynamic sensitivities equivalent to that of the primary spindle afferents. Although the discharge of some area 3a neurons also reflected differences in muscle length, most area 3a neurons had low position sensitivities. One unit type in area 3a did not respond to maintained muscle stretch and signaled only velocity of stretch.4. Units in area 4 had position sensitivities equivalent to that of primary and secondary spindle afferents. Although the discharge of some area 4 units reflected different velocities of muscle stretch, these units had dynamic sensitivities similar to those of secondary spindle afferents rather than those of primary afferents. One type of unit in area 4 had no dynamic component to muscle stretch and signaled only muscle length.5. The results demonstrate that there is a transfer of dynamic and position sensitivity from spindle afferents to cortical neurons. Furthermore, data processing has occurred because some units respond only to the steady-state length of muscle, while other units encode only the dynamic phase of stretch. This behavior is different from the responses to ramp stretch of either group I or group II muscle afferents in the baboon.6. The results demonstrate that single units in cerebral cortex can encode the information transmitted to the central nervous system by muscle spindle afferents. The purpose for which this information is used remains undetermined.

scholarly journals The primary structure of alamethicin

1970 ◽  
Vol 117 (4) ◽  
pp. 757-766 ◽  
Author(s):  
J. W. Payne ◽  
R. Jakes ◽  
B. S. Hartley
Keyword(s):  
Action Potentials ◽  
Model Building ◽  
Cyclic Peptide ◽  
Peptide Bond ◽  
Complete Sequence ◽  
Carboxyl Group ◽  
Imino Group ◽  
Synthetic Membranes ◽  
Enzymic Digestion

Alamethicin, an antibiotic that can transport cations and induce action potentials in synthetic membranes, is shown to be a cyclic peptide with 18 residues including 7-α-aminoisobutyric acid residues, two glutamine residues and one free carboxyl group. The composition indicates microheterogeneity. Alamethicin itself and many peptides derived from it are immune to enzymic digestion, but specific partial acid cleavages have allowed determination of the complete sequence. Diborane reduction has shown that the α-carboxyl group of glutamine-18 is free, but the ring is formed by a peptide bond between the imino group of proline-1 and the γ-carboxyl group of glutamic acid-17. The structure is contrasted with that of other cation-transporting antibiotics. Model building allows a structure that could stack to form a tunnel with a lipophilic exterior and hydrophilic interior and flexible internal arms formed by the pendant C-terminal glutamine residue.

scholarly journals Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRPα-mCherry reporter mice

2016 ◽  
Vol 311 (5) ◽  
pp. G880-G894 ◽  
Author(s):  
Nick J. Spencer ◽  
Julian Sorensen ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Marcello Costa ◽  
...  
Keyword(s):  
Action Potentials ◽  
Visceral Pain ◽  
Sensory Transduction ◽  
Calcium Transients ◽  
Sensory Stimuli ◽  
Myenteric Neurons ◽  
Visceral Organs ◽  
Major Class ◽  
Reporter Mice ◽  
Spinal Afferents

In vertebrates, visceral pain from internal organs is detected by spinal afferents, whose cell bodies lie in dorsal root ganglia (DRG). Until now, all recordings from spinal afferents have been restricted to recording transmission of action potentials along axons, or from cell bodies lying outside their target organ, which is not where sensory transduction occurs. Our aim was to record directly from a major class of spinal afferent within visceral organs, where transduction of sensory stimuli into action potentials occurs. Using novel calcitonin gene-related peptide (CGRP)α reporter mice, DRG neurons expressed mCherry, including nerve axons within viscera. In colon, a minority of total CGRP immunoreactivity was attributed CGRPα. In isolated unstretched colon, calcium imaging from CGRPα-expressing varicose axons did not detect resolvable calcium transients. However, noxious levels of maintained circumferential stretch to the colon induced repetitive calcium transients simultaneously in multiple neighboring varicosities along single mCherry-expressing axons. Discrete varicosities could generate unitary calcium transients independently of neighboring varicosities. However, axons expressing mCherry only generated coordinated calcium transients when accompanied by simultaneous activation of multiple varicosities along that axon. Simultaneous imaging from different classes of myenteric neurons at the same time as mCherry-expressing axons revealed coordinated calcium transients in multiple myenteric neurons, independent of activity in mCherry-expressing axons. CGRPα-expressing axon terminals preferentially responded to heat, capsaicin, and low pH. We show that direct recordings can be made from the major class of peptidergic spinal afferent that contributes to visceral nociception. This approach can provide powerful insights into transduction of stimuli in viscera.

Representations of the Bondi—Metzner—Sachs group I. Determination of the representations

1972 ◽  
Vol 330 (1583) ◽  
pp. 517-535 ◽  
Keyword(s):  
Elementary Particles ◽  
Wave Functions ◽  
Unitary Representations ◽  
Continuous Spin ◽  
Gravitational Fields ◽  
Group I ◽  
Irreducible Unitary Representations ◽  
Infinite Component ◽  
Striking Contrast

Following a historical introduction, it is suggested that irreducible unitary representations of the Bondi-Metzner-Sachs group may be used to classify elementary particles in a quantum theory which takes ‘asymptotically flat5 gravitational fields into account. The unitary representations of the group induced from irreducible unitary representations of the connected little groups are all determined. It is shown that the connected little groups are all compact, so that the ‘spins’ of the corresponding particles are necessarily discrete, and the wave functions have a finite number of components. Furthermore, the spins are of precisely the observed type. This is in striking contrast to the situation for the Poincare group, for which the spins may be discrete or continuous. (The continuous spin wave functions are infinite-component.) It is concluded that the B.M.S. group may provide an explanation for the observed discreteness of the spins of elementary particles.

Cerebellar cortical activity during stretch of antagonist muscles

1986 ◽  
Vol 64 (9) ◽  
pp. 1202-1213 ◽  
Author(s):  
Daniel Bourbonnais ◽  
Charles Krieger ◽  
Allan M. Smith
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Muscle Length ◽  
Thoracic Spinal Cord ◽  
Muscle Stretch ◽  
Thoracic Spinal ◽  
Antagonist Muscles ◽  
Discharge Patterns ◽  
Dynamic Stretch ◽  
Complex Spikes

Single unit activity was recorded from the anterior lobe of the cerebellum during ramp and hold stretches of limb muscles in chloralose anesthetized cats. The activity of 95 "phasic" units showed a transient response during dynamic stretch of at least one muscle usually lasting for less than 350 ms following the stimulus onset. The activity of 59 phasic–tonic units was modified not only during dynamic stretch but also during the 1 s of maintained muscle length. All Purkinje cells, identified by their complex spikes, that responded to muscle stretch demonstrated exclusively phasic changes in discharge. Fourteen of 25 Purkinje cells (56%) responded to stretch of both antagonist muscles and these responses were always similar rather than reciprocal. From the 129 units without complex spikes, 70 demonstrated phasic discharge patterns whereas 59 had tonic responses. Seventy-five (59%) of these unidentified units revealed convergent responses to stretch of both antagonists, compared with 54 which responded to stretch of one muscle only. Of the unidentified units receiving convergent afferents from antagonist muscles, 62 (83%) had similar responses and only 13 (17%) had reciprocal reactions. There appeared to be no evidence that muscle afferents alone can induce reciprocal discharge patterns in Purkinje neurons of the cerebellar cortex. The firing frequency of some phasic–tonic units was correlated with both the velocity and amplitude of muscle stretch. No Purkinje cells were found with activity related to either velocity or amplitude of muscle stretch. One phasic and seven phasic–tonic unidentified units were activated at fixed latencies following trains of electrical stimulation applied to the thoracic spinal cord at frequencies exceeding 200 Hz, implying they were terminal portions of mossy fibers originating from direct spinocerebellar tracts. A few recordings of compound potentials were presumed to arise from the cerebellar glomeruli. The changing form of one of these potentials suggested that the glomerulus might be a site at which somatosensory peripheral information is modified by the cerebellar cortex.

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