Neurotrophins and synaptic plasticity in the mammalian spinal cord

Mendell, Lorne M.; Munson, John B.; Arvanian, Victor L.

doi:10.1111/j.1469-7793.2001.0091b.x

Cited by 84 publications

(63 citation statements)

References 50 publications

(63 reference statements)

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“…Both negative and positive injury signals have been shown to initiate synaptic change (Lessmann, 1998;Mendell et al, 1999;Woolf and Costigan, 1999;Mendell and Arvanian, 2002;Kohno et al, 2003;Du and Poo, 2004;Sung et al, 2004;McMahon et al, 2005). For IA-MN synapses, deprivation of muscle-derived neurotrophin NT3 may contribute to the decline in EPSP amplitude that occurs Ͼ1 week after nerve section (Mendell et al, 2001). However, the enlargement that occurs earlier after nerve crush is probably not initiated by a negative injury signal, because we found that blocking axon transport in intact nerves had no discernable short-term effect on IA-MN synaptic function.…”

Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 40%

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Bichler¹,

Nakanishi²,

Wang³

et al. 2007

J. Neurosci.

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Peripheral nerve crush initiates a robust increase in transmission strength at spinal synapses made by axotomized group IA primary sensory neurons. To study the injury signal that initiates synaptic enhancement in vivo, we designed experiments to manipulate the enlargement of EPSPs produced in spinal motoneurons (MNs) by IA afferents 3 d after nerve crush in anesthetized adult rats. If nerve crush initiates IA EPSP enlargement as proposed by reducing impulse-evoked transmission in crushed IA afferents, then restoring synaptic activity should eliminate enlargement. Daily electrical stimulation of the nerve proximal to the crush site did, in fact, eliminate enlargement but was, surprisingly, just as effective when the action potentials evoked in crushed afferents were prevented from propagating into the spinal cord. Consistent with its independence from altered synaptic activity, we found that IA EPSP enlargement was also eliminated by colchicine blockade of axon transport in the crushed nerve. Together with the observation that colchicine treatment of intact nerves had no short-term effect on IA EPSPs, we conclude that enhancement of IA-MN transmission is initiated by some yet to be identified positive injury signal generated independent of altered synaptic activity. The results establish a new set of criteria that constrain candidate signaling molecules in vivo to ones that develop quickly at the peripheral injury site, move centrally by axon transport, and initiate enhanced transmission at the central synapses of crushed primary sensory afferents through a mechanism that can be modulated by action potential activity restricted to the axons of crushed afferents.

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Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 40%

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Bichler¹,

Nakanishi²,

Wang³

et al. 2007

J. Neurosci.

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“…Homonymous EPSPs are not potentiated in mlc/NT3 mice, however. The absence of potentiation is unlikely to result from saturation because these EPSPs can be potentiated in adult and neonatal rats by treatment with NT3 (Munson et al, 1997;Mendell et al, 2001;Arvanian et al, 2003). For the mice used in this study, the distribution of hom- onymous EPSP amplitudes in mlc/NT3 mice also argues against a saturation of these potentials in normal mice.…”

Section: Discussionmentioning

confidence: 80%

“…Chronic exposure to elevated levels of NT3 increase synaptic inputs to MNs in neonatal rats, and exogenous NT3 applied to the cut central end of muscle nerves potentiates synaptic inputs from Ia axons onto MNs above their normal amplitude even in adult rats and cats (Munson et al, 1997;Mendell et al, 2001;Arvanian et al, 2003). Exposure to elevated NT3 levels prenatally might therefore cause a similar increase in the strength of all Ia-MN synapses.…”

Section: Discussionmentioning

confidence: 97%

“…Postnatally, NT3 expressed by muscle spindles maintains synaptic function between Ia afferents and MNs. If a motor nerve is cut in adult cats or rats, Ia-MN connections are reduced (Goldring et al, 1980) but can be restored and even made larger than normal by applying NT3 to the cut proximal end of the nerve (Munson et al, 1997;Mendell et al, 2001). NT3 injections also restore the loss of Ia-MN connectivity in Egr3 null mutant mice, in which NT3 expression by intrafusal fibers is eliminated (Chen et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Prenatal Exposure to Elevated NT3 Disrupts Synaptic Selectivity in the Spinal Cord

Wang¹,

Li²,

Taylor³

et al. 2007

J. Neurosci.

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Monosynaptic connections between muscle spindle (Ia) afferents and motoneurons (MNs), the central portion of the stretch reflex circuit, are highly specific, but the mechanisms underlying this specificity are primarily unknown. In this study, we report that embryonic overexpression of neurotrophin-3 (NT3) in muscles disrupts the development of these specific Ia-MN connections, using transgenic (mlc/NT3) mice that express elevated levels of NT3 in muscles during development. In mlc/NT3 mice, there is a substantial increase in the amplitudes of monosynaptic EPSPs evoked by Ia afferents in MNs as measured with extracellular recordings from ventral roots. Despite this increased functional projection of Ia afferents, there is no obvious change in the anatomical density of Ia projections into the ventral horn of the spinal cord. Intracellular recordings from MNs revealed a major disruption in the pattern of Ia-MN connections. In addition to the normal connections between Ia afferents and MNs supplying the same muscle, there were also strong monosynaptic inputs from Ia afferents supplying unrelated muscles, which explains the increase seen in extracellular recordings. There was also a large variability in the strength of Ia input to individual MNs, both from correct and incorrect Ia afferents. Postnatal muscular administration of NT3 did not cause these changes in connectivity. These results indicate that prenatal exposure to elevated levels of NT3 disrupts the normal mechanisms responsible for synaptic selectivity in the stretch reflex circuit.

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“…Some increase synaptic efficacy by increasing NMDA excitability, perhaps by phosphorylating the NR2A subunit of the NMDA-gated ionic channel. 64,66,67 Others decrease GABA synaptic inhibition acutely. 64 The enhancement of excitatory synapses and reduction of synaptic inhibition may contribute, along with receptor upregulation, to the emergence from spinal shock by 1-3 days postinjury.…”

Section: Phase 2: Initial Reflex Return (1-3 Days)mentioning

confidence: 99%

Spinal shock revisited: a four-phase model

et al. 2004

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Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel fourphase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.

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Neurotrophins and synaptic plasticity in the mammalian spinal cord

Cited by 84 publications

References 50 publications

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Prenatal Exposure to Elevated NT3 Disrupts Synaptic Selectivity in the Spinal Cord

Spinal shock revisited: a four-phase model

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