Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord

Arvanian, Victor L.; Mendell, Lorne M.

doi:10.1046/j.0953-816x.2001.01811.x

Cited by 52 publications

(57 citation statements)

References 44 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This strengthening involves the action of NMDA receptors known to be functional on motoneurons, particularly in neonates (Ziskind-Conhaim, 1990;Arvanian et al, 2004). Furthermore, motoneuron NMDA receptor activation is enhanced by administration of the neurotrophins NT-3 and BDNF (Arvanov et al, 2000;Arvanian and Mendell, 2001), both of which are elevated in hindlimb muscle and/or spinal cord by step training (Gomez-Pinilla et al, 2001; Hutchinson et al, 2004). Recent evidence indicates that joint treatment with BDNF and NT-3 is able to improve stepping ability to the same degree as treadmill training alone in spinal cats, although the combination yields the best results (Boyce et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Petruska¹,

Ichiyama²,

Jindrich³

et al. 2007

J. Neurosci.

139

116

View full text Add to dashboard Cite

Although recovery from spinal cord injury is generally meager, evidence suggests that step training can improve stepping performance, particularly after neonatal spinal injury. The location and nature of the changes in neural substrates underlying the behavioral improvements are not well understood. We examined the kinematics of stepping performance and cellular and synaptic electrophysiological parameters in ankle extensor motoneurons in nontrained and treadmill-trained rats, all receiving a complete spinal transection as neonates. For comparison, electrophysiological experiments included animals injured as young adults, which are far less responsive to training. Recovery of treadmill stepping was associated with significant changes in the cellular properties of motoneurons and their synaptic input from spinal white matter [ipsilateral ventrolateral funiculus (VLF)] and muscle spindle afferents. A strong correlation was found between the effectiveness of step training and the amplitude of both the action potential afterhyperpolarization and synaptic inputs to motoneurons (from peripheral nerve and VLF). These changes were absent if step training was unsuccessful, but other spinal projections, apparently inhibitory to step training, became evident. Greater plasticity of axonal projections after neonatal than after adult injury was suggested by anatomical demonstration of denser VLF projections to hindlimb motoneurons after neonatal injury. This finding confirmed electrophysiological measurements and provides a possible mechanism underlying the greater training susceptibility of animals injured as neonates. Thus, we have demonstrated an "age-at-injury"-related difference that may influence training effectiveness, that successful treadmill step training can alter electrophysiological parameters in the transected spinal cord, and that activation of different pathways may prevent functional improvement.

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Petruska¹,

Ichiyama²,

Jindrich³

et al. 2007

J. Neurosci.

139

116

View full text Add to dashboard Cite

show abstract

“…On the other hand, BDNF has been shown to inhibit glutamatergic signaling in the nucleus of the solitatry tract (Balkowiec et al, 2000) and in lateral motor nuclei in the spinal cord (Seebach et al, 1999;Arvanian and Mendell, 2001). It might therefore have been argued that endogenous BDNF prevents complete recovery by inhibiting glutamatergic transmission in the dorsal horn.…”

Section: Potential Mechanisms Of Spontaneous Recovery After Drimentioning

confidence: 99%

Endogenous TrkB Ligands Suppress Functional Mechanosensory Plasticity in the Deafferented Spinal Cord

Ramer

McPhail²,

Borisoff³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal cord. Although primary afferents do not regenerate to their original targets, spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter after DRI. Because endognous BDNF and NT-3 have well established roles in synaptic and axonal plasticity, we hypothesized that they contributed to spontaneous recovery after DRI. We first developed a model of DRI-induced mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold cutaneous mechanosensation that spontaneously improved within 10 d but did not recover completely. To determine the effects of endogenous BDNF and NT-3, we administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period. To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d after DRI. It also stimulated mechanosensory axon sprouting but prevented deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on low-threshold mechanosensory behavior or axonal plasticity. There was no mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI (despite significantly reducing rhizotomy-induced cold pain), indicating that neuromodulatory effects of BDNF did not underlie mechanosensory recovery. Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc treatment occurred independent of signaling by other neurotrophins. These results illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on mechanosensation and mechanosensory primary afferent axons after spinal deafferentation.

show abstract

“…Following the binding of BDNF to TrkB on those neurons, the receptor is activated by autophosphorylation mechanisms, allowing an intracellular signaling cascade that leads to a positive modulation of the glutamate receptor NMDA, through phosphorylation of its NR1 subunit (Di Luca et al, 2001;Slack and Thompson, 2002;Slack et al, 2004) and possibly NR2 subunit, hence exacerbating the glutamatergic transmission (Kerr et al, 1999;Heppenstall and Lewin, 2001;Arvanian and Mendell, 2001;Groth and Aanonsen, 2002), thereby increasing the response of postsynaptic neurons. The ultimate functional consequence of this biochemical activation is increased neuronal activation of the spinothalamic neurons and hence increased transmission of pain-related signals.…”

Section: Functional Significance Of Trkb Expression On Stt Neuronsmentioning

confidence: 99%

TrkB expression and phospho-ERK activation by brain-derived neurotrophic factor in rat spinothalamic tract neurons

et al. 2005

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) is a neurotrophin implicated in the phenomena of synaptic plasticity in the adult. It is found in terminals of nociceptive primary afferents. Following a pain-related stimulus, it is released in the spinal cord, where it activates its high-affinity receptor TrkB, leading to the phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK). A large body of evidence suggests that BDNF has a positive neuromodulatory effect on glutamate transmission in the spinal cord. However, none of these studies examined anatomically whether projection neurons known to be involved in transmission of nociceptive inputs express BDNF's receptor. Because the spinothalamic tract (STT) is a well-characterized pathway for its role in the transfer and integration of sensory and nociceptive informations, this study in rats aimed to 1) determine whether neurons of the STT pathway express the TrkB receptor, 2) establish the rostrocaudal and laminar distribution of STT-TrkB neurons in the whole spinal cord, and 3) test the potential functionality of TrkB expression in these cells by investigating the ability of BDNF to activate the MAP kinase ERK. Using tract tracing coupled to immunofluorescent labeling for TrkB, we observed that in all levels of the spinal cord most STT neurons were immunoreactive for TrkB. Furthermore, microinjections of BDNF into the spinal cord or release of endogenous BDNF by intraplantar injection of capsaicin activated ERK phosphorylation in TrkB-containing STT neurons. These data suggest an important role for BDNF in nociception as an activator of spinothalamic projection neurons.

show abstract

Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord

Cited by 52 publications

References 44 publications

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Endogenous TrkB Ligands Suppress Functional Mechanosensory Plasticity in the Deafferented Spinal Cord

TrkB expression and phospho-ERK activation by brain-derived neurotrophic factor in rat spinothalamic tract neurons

Contact Info

Product

Resources

About