Muscle Spindle-Derived Neurotrophin 3 Regulates Synaptic Connectivity between Muscle Sensory and Motor Neurons

Chen, Hsiao Huei; Tourtellotte, Warren G.; Frank, Eric

doi:10.1523/jneurosci.22-09-03512.2002

Cited by 98 publications

(112 citation statements)

References 41 publications

(63 reference statements)

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“…The effectiveness of these injections in raising levels of NT3 was confirmed by making intracellular recordings from MNs in Egr3 null mutant mice. These mice have weak Ia-MN synapses resulting from an absence of NT3 in postnatal muscle spindles, but functional transmission can be restored by postnatal NT3 injections (Chen et al, 2002). In the present experiments, these injections increased the homonymous inputs to Q and Add MNs in Egr3 null mutant mice from 0.08 to 11.45 mV, which is approximately the normal level (data not shown).…”

Section: Postnatal Nt3 Injections Do Not Disrupt Selectivity Of Ia-mnsupporting

confidence: 57%

“…Postnatal injections of NT3 into Egr3 null mutant mice, for example, rescue the large reduction in these connections caused by the absence of NT3 in postnatal spindles in these mice (Chen et al, 2002). Although we did not observe an increase in homonymous EPSP amplitudes in mlc/NT3 mice (Fig.…”

Section: Postnatal Nt3 Injections Do Not Disrupt Selectivity Of Ia-mnmentioning

confidence: 61%

“…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). The NT3 released by muscle spindles may therefore modulate the strength of synaptic transmission between Ia afferents and MNs throughout life.…”

Section: Discussionmentioning

confidence: 98%

See 2 more Smart Citations

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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Section: Postnatal Nt3 Injections Do Not Disrupt Selectivity Of Ia-mnsupporting

confidence: 57%

Section: Postnatal Nt3 Injections Do Not Disrupt Selectivity Of Ia-mnmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

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

Wang¹,

Li²,

Taylor³

et al. 2007

J. Neurosci.

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show abstract

“…111 Both corticospinal inputs and IA afferents increase axon growth in response to the neurotrophin NT3. 90,[112][113][114][115][116] NTs like NT3, promoting both IA afferent and corticospinal neurite growth, could underlie competitive synapse growth. In subjects with chronic incomplete SCI and hyper-reflexia, motor neurons are often either under voluntary control or under reflex control; thus, either one or the other input comes to dominate control over a given motor neuron.…”

Section: Clinical Implications Of Spinal Shockmentioning

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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“…Thus, sensorin, like neurotrophins such as BDNF, can have multiple functions, including producing neurotransmitter-like responses in some follower cells and acting as a neuromodulator in producing longterm facilitation when it interacts with autoreceptors whose signaling pathway is also activated by the stimuli required to produce long-term facilitation (Hu et al, 2004). Neurotrophins and their receptors are one group of factors that contribute not only to proliferation, survival, and early differentiation of neurons but also to the formation and maintenance of peripheral synapses (Schafer et al, 1983;Gonzalez et al, 1999;Wells et al, 1999;Lockhart et al, 2000;Belluardo et al, 2001;Chen et al, 2002) and the formation, fine-tuning, maintenance, and longterm modulation of central synapses (Cabelli et al, 1995(Cabelli et al, , 1997Kang and Schuman, 1995;McAllister et al, 1997;Martinez et al, 1998;Cohen-Cory, 2002;Vicario-Abejon et al, 2002).…”

Section: Sensorin Secretion Regulates Synapse Formation and Maturationmentioning

confidence: 99%

Target-Dependent Release of a Presynaptic Neuropeptide Regulates the Formation and Maturation of Specific Synapses inAplysia

Hu¹,

Goldman²,

Wu³

et al. 2004

J. Neurosci.

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The correct wiring of neurons is critical for the normal functioning of the nervous system. Sensory neurons of Aplysia form synapses with specific postsynaptic targets. Interaction with appropriate target cells in culture induces a significant increase in axon growth, the number of sensory neuron varicosities with release sites contacting the target, and regulates the expression and distribution of mRNAs encoding presynaptic proteins such as syntaxin and the sensory neuron-specific neuropeptide sensorin. Synapse stabilization is accompanied by the maintenance of presynaptic varicosities and target-dependent regulation of mRNA distributions. We report here that specific targets induce the release of sensorin from sensory neurons, which then regulates synaptic efficacy, axonal growth associated with synapse formation, the maintenance of synaptic contacts, and the specific distribution of mRNAs. Bath application of an antisensorin antibody during the early phase of synapse formation blocked the expected increase in synaptic strength, the growth and formation of new presynaptic varicosities, and the target-dependent regulation of mRNA distribution. In contrast, bath application of sensorin accelerated the increase in synaptic strength and enhanced the formation of new varicosities and target-dependent regulation of mRNA distribution in sensory neurons. As synapses stabilize, sensorin secretion declines but is required for the maintenance of synaptic efficacy, presynaptic varicosities, and mRNA distributions. These results suggest that a retrograde target signal regulates the secretion and actions of a presynaptic neuropeptide critical for the formation and maintenance of specific synapses.

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Muscle Spindle-Derived Neurotrophin 3 Regulates Synaptic Connectivity between Muscle Sensory and Motor Neurons

Cited by 98 publications

References 41 publications

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

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

Spinal shock revisited: a four-phase model

Target-Dependent Release of a Presynaptic Neuropeptide Regulates the Formation and Maturation of Specific Synapses inAplysia

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