Axonal regeneration of descending brain neurons in larval lamprey demonstrated by retrograde double labeling

Zhang, Lei; McClellan, Andrew D.

doi:10.1002/(sici)1096-9861(19990809)410:4<612::aid-cne8>3.0.co;2-r

Cited by 25 publications

(19 citation statements)

References 59 publications

(94 reference statements)

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“…Thus, some axotomized neurons that did not recover normal firing patterns appeared to regenerate their axons but perhaps not far enough to make substantial numbers of synapses below the lesion (see Discussion). For example, at relatively long recovery times (16 weeks) after complete transections of the rostral spinal cord, only ϳ30 -50% of the large B cells (B1, B3, and B4) regenerate their axons for at least ϳ10 mm below the lesion (Davis and McClellan, 1994b) (also see Zhang and McClellan, 1999).…”

Section: Firing Patterns Of Identified Rs Neuronsmentioning

confidence: 99%

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

McClellan¹,

Kovalenko²,

Benes³

et al. 2008

J. Neurosci.

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In larval lamprey, hemitransections were performed on the right side of the rostral spinal cord to axotomize ipsilateral reticulospinal (RS) neurons. First, at short recovery times (2-3 weeks), uninjured RS neurons contralateral to hemitransections fired a smooth train of action potentials in response to sustained depolarization, whereas axotomized neurons fired a single short burst or short repetitive bursts. For uninjured RS neurons, the afterpotentials of action potentials had three components: fast afterhyperpolarization (fAHP), afterdepolarizing potential (ADP), and slow AHP (sAHP) that was attributable to calcium influx via high-voltage-activated (HVA) (N-and P/Q-type) calcium channels and calcium-activated potassium channels (SKKCa). For axotomized RS neurons, the fAHP was significantly larger than for uninjured neurons, and the ADP and sAHP were absent or significantly reduced. Second, at relatively long recovery times (12-16 weeks), axotomized RS neurons displayed firing patterns and afterpotentials that were similar to those of uninjured neurons. Third, mRNA levels of lamprey HVA calcium and SKKCa channels in axotomized RS neurons were significantly reduced at short recovery times and restored at long recovery times. Fourth, blocking calcium channels in uninjured RS neurons resulted in altered firing patterns that resembled those produced by axotomy. We demonstrated previously that lamprey RS neurons in culture extend neurites, and calcium influx results in inhibition of neurite outgrowth or retraction. Together, these results suggest that the downregulation of Ca 2ϩ channels in axotomized RS neurons, and the associated reduction in calcium influx, maintain intracellular calcium levels in a range that is permissive for axonal regeneration.

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Section: Firing Patterns Of Identified Rs Neuronsmentioning

confidence: 99%

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

McClellan¹,

Kovalenko²,

Benes³

et al. 2008

J. Neurosci.

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“…After possible regeneration, a second tracer is applied below the transection site but above the application site for the first tracer. Although there are some inherent limitations to double‐labeling experiments (see discussion in Zhang and McClellan, 1999a), ideally, double‐labeled neurons regenerated their axons, whereas neurons labeled only with the second tracer were uninjured and subsequently elongated their axons through the lesion site. Following spinal cord injury in salamander, zebrafish, embryonic chick, young opossum, or neonatal rat, double labeling of descending brain neurons is in the range of approximately 5–45% (Davis et al, 1989; Garner et al, 1990; Xu and Martin, 1991; Bates and Stelzner, 1993; Hasan et al, 1993; Becker et al, 1997; Wang et al, 1998).…”

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confidence: 99%

“…Results from double‐labeling experiments indicate that many descending brain neurons, including unidentified reticulospinal (RS) neurons that are thought to initiate locomotion, regenerate their axons following spinal cord transection (Zhang and McClellan. 1999a). However, these previous studies do not exclude the possibility that restoration of brain‐spinal cord projections following spinal cord injury might also be due to the addition of new descending projections.…”

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confidence: 99%

Increase in descending brain–spinal cord projections with age in larval lamprey: Implications for spinal cord injury

Zhang¹,

Palmer²,

McClellan³

2002

J of Comparative Neurology

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The purpose of this study was to determine whether new descending brain-spinal cord projections are added with age in larval lamprey and might contribute substantially to restoration of these projections following spinal cord injury. Retrograde horseradish peroxidase (HRP) labeling of descending brain neurons was performed in "young" and "old" larval lamprey that differed in age by at least one year. In old larval lamprey, significantly more descending brain neurons projected to specific rostral levels of the spinal cord than in young animals. Furthermore, in young and old lamprey, the main morphological change in Müller and Mauthner cells was an increase in soma size. The major conclusion from the present study is that in larval lamprey, some new brain-spinal cord projections are added with age that could be due to axonal elongation by preexisting brain neurons and/or descending projections from new neurons (i.e., neurogenesis or maturation of incompletely differentiated neurons). Following spinal cord transections, the numbers of descending projections were not significantly different than those in normal, unlesioned animals. Thus, some new descending projections are added with age, but at a relatively slow rate, and the rate does not appear to be affected significantly by spinal cord transections. Together, the present results and those from our recent double-labeling study suggest that following spinal cord transection in larval lamprey, axonal regeneration by descending brain neurons, rather than the relatively slow addition of new brain-spinal cord projections with age, probably accounts for the majority of restored projections and recovery of locomotor function

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“…Cell body responses probably play a role in enhancing restoration of descending brain-spinal cord projections in larval lamprey with CLs. Recent studies strongly suggest that axonal regeneration is the major mechanism for restoration of descending brain-spinal cord projections and recovery of locomotor function in spinal cord-transected larval lamprey (Zhang and McClellan, 1999;Zhang et al, 2002). Thus, a better understanding of the mechanisms underlying the enhancement of axonal regeneration by CLs might suggest possible strategies for regulating regeneration under conditions in which axonal outgrowth is limited.…”

Section: Discussionmentioning

confidence: 99%

Conditioning lesions enhance axonal regeneration of descending brain neurons in spinal‐cord‐transected larval lamprey

Zhang¹,

Palmer²,

McClellan³

2004

J of Comparative Neurology

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In larval lamprey, with increasing recovery times after a transection of the rostral spinal cord, there is a gradual recovery of locomotor behavior, and descending brain neurons regenerate their axons for progressively greater distances below the transection site. In the present study, spinal cord "conditioning lesions" (i.e., transections) were performed in the spinal cord at 30% body length (BL; normalized distance from the head) or 50% BL. After various "lesion delay times" (D), a more proximal spinal cord "test lesion" (i.e., transection) was performed at 10% BL, and then, after various recovery times (R), horseradish peroxidase was applied to the spinal cord at 20% BL to determine the extent of axonal regeneration of descending brain neurons. Conditioning lesions at 30% BL, lesion delay times of 2 weeks, and recovery times of 4 weeks (D-R = 2-4 group) resulted in a significant enhancement of axonal regeneration for the total numbers of descending brain neurons as well as neurons in certain brain cell groups compared to control animals without conditioning lesions. Experiments with hemiconditioning lesions, which reduce interanimal variability, confirmed that conditioning lesions do significantly enhance axonal regeneration and indicate that axotomy rather than diffusible factors released at the injury site is primarily involved in this enhancement. Results from the present study suggest that conditioning lesions "prime" descending brain neurons via cell body responses and enhance subsequent axonal regeneration, probably by reducing the initial delay and/or increasing the initial rate of axonal outgrowth. Indexing termsaxotomy; reticulospinal neurons; spinal cord injury; conditioning lesion; test lesion When neurons are axotomized, they often are "primed" for possible subsequent axonal regeneration. If the axons of these neurons then receive a second "test lesion," often proximal to the first "conditioning lesion" (CL), regeneration can be enhanced compared with that of neurons without previous CLs. This phenomenon of enhanced axonal regeneration is called the "CL effect" (Forman et al., 1980). Because most studies of CL effects have been performed on nerves (e.g., sciatic nerve or optic nerve), crush injuries usually are employed for both the conditioning and the test lesions.After an initial CL, there are a series of morphological, physiological, and biochemical changes in axotomized neurons (McQuarrie and Grafstein, 1982;Redshaw and Bisby, 1987 Perry et al., 1987;Jacob and McQuarrie, 1991;Tetzlaff et al., 1996). Investigating the effects of CLs potentially might clarify the mechanisms that regulate neural regeneration, and it might then be possible to manipulate these mechanisms to enhance axonal regeneration. For example, a CL of the peripheral branch of neurons in dorsal root ganglia (DRG) raises cAMP levels and promotes axonal regeneration of the central branches of these neurons, and this effect can be mimicked by injection of cAMP in DRG (Qiu et al., 2002).The effects of CLs have been invest...

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Axonal regeneration of descending brain neurons in larval lamprey demonstrated by retrograde double labeling

Cited by 25 publications

References 59 publications

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

Increase in descending brain–spinal cord projections with age in larval lamprey: Implications for spinal cord injury

Conditioning lesions enhance axonal regeneration of descending brain neurons in spinal‐cord‐transected larval lamprey

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