A chronically implantable device for the controlled delivery of substances, and stimulation and recording of activity in severed nerves

Carrizosa, María A. Davis‐López de; Tena, Juan J.; Benítez‐Temiño, Beatriz; Morado-Díaz, Camilo J.; Pastor, Ángel M.; Cruz, Rosa R. de la

doi:10.1016/j.jneumeth.2007.08.021

Cited by 9 publications

(8 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This also prevented axonal reinnervation of extraocular muscles or any other structure (Baker et al, 1981;DelgadoGarcía et al, 1988). This so-called intraorbitary device consisted of a chamber with two pieces of tubing inserted for the push-pull of fluid (Davis-Ló pez de Carrizosa et al, 2008). The chamber was made with a standard polypropylene pipette tip shortened to ϳ15 mm, thus giving it a conical shape.…”

Section: Methodsmentioning

confidence: 99%

“…A possible role for NGF in regulating the morphophysiological characteristics of extraocular motoneurons and its afferent inputs has not yet been studied. To analyze this possibility, we induced alterations in the levels of NGF by either axotomy or externally applying NGF to the stump of the sectioned nerve (Davis-Ló pez de Carrizosa et al, 2008). Then, we examined the actions of NGF through its two receptors, neurotrophin receptor p75 (p75 NTR ) and TrkA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Carrizosa¹,

Morado-Díaz²,

Morcuende³

et al. 2010

Journal of Neuroscience

View full text Add to dashboard Cite

Target-derived neurotrophins exert powerful synaptotrophic actions in the adult brain and are involved in the regulation of different forms of synaptic plasticity. Target disconnection produces a profound synaptic stripping due to the lack of trophic support. Consequently, target reinnervation leads to synaptic remodeling and restoration of cellular functions. Extraocular motoneurons are unique in that they normally express the TrkA neurotrophin receptor in the adult, a feature not seen in other cranial or spinal motoneurons, except after lesions such as axotomy or in neurodegenerative diseases like amyotrophic lateral sclerosis. We investigated the effects of nerve growth factor (NGF) by retrogradely delivering this neurotrophin to abducens motoneurons of adult cats. Axotomy reduced the density of somatic boutons and the overall tonic and phasic firing modulation. Treatment with NGF restored synaptic inputs and firing modulation in axotomized motoneurons. When K252a, a selective inhibitor of tyrosine kinase activity, was applied to specifically test TrkA effects, the NGF-mediated restoration of synapses and firing-related parameters was abolished. Discharge variability and recruitment threshold were, however, increased by NGF compared with control or axotomized motoneurons. Interestingly, these parameters returned to normal following application of REX, an antibody raised against neurotrophin receptor p75 (p75 NTR ). In conclusion, NGF, acting retrogradely through TrkA receptors, supports afferent boutons and regulates the burst and tonic signals correlated with eye movements. On the other hand, p75 NTR activation regulates recruitment threshold, which impacts on firing regularity. To our knowledge, this is the first report showing powerful synaptotrophic effects of NGF on motoneurons in vivo.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Carrizosa¹,

Morado-Díaz²,

Morcuende³

et al. 2010

Journal of Neuroscience

View full text Add to dashboard Cite

show abstract

“…For the delivery of neurotrophins, we implanted the stump of the abducens nerve in a custom-made chamber to control the milieu that bathed it and to prevent axonal reinnervation of any orbital structure or other extraocular muscles (Delgado-García et al, 1988). The intraorbitary device consisted of a chamber that had two pieces of tubing inserted for fluid replacement and two electrodes as we recently described (Davis-Ló pez de Carrizosa et al, 2008). The chamber was made with a standard polypropylene pipette tip shortened to ϳ15 mm and thus having conical shape.…”

Section: Methodsmentioning

confidence: 99%

“…It is well known that these changes in electrical and synaptic properties revert with target reinnervation (DelgadoGarcía et al, 1988;Brännström and Kellerth, 1999) and remain altered when reinnervation is prevented (Sumner, 1976;Pinter and Vanden Noven, 1989;Vanden Noven and Pinter, 1989). Thus, for preventing random target reinnervation and/or reestablishment of trophic support from orbital tissues, we devised a method for controlling the extracellular environment that bathes the axonal stumps (Davis-Ló pez de Carrizosa et al, 2008). We cannot ascertain whether neurotrophins signaled to afferents through transsynaptic translocation, like tetanus toxin does (González-Forero et al, 2005;Rind et al, 2005), or induced in the motoneurons the signal for alterations in their synaptic coverage.…”

Section: Alterations Of Target-derived Trophic Support Determine the mentioning

confidence: 99%

Complementary Actions of BDNF and Neurotrophin-3 on the Firing Patterns and Synaptic Composition of Motoneurons

Carrizosa¹,

Morado-Díaz²,

Tena³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

Neurotrophins, as target-derived factors, are essential for neuronal survival during development, but during adulthood, their scope of actions widens to become also mediators of synaptic and morphological plasticity. Target disconnection by axotomy produces an initial synaptic stripping ensued by synaptic rearrangement upon target reinnervation. Using abducens motoneurons of the oculomotor system as a model for axotomy, we report that trophic support by brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or a mixture of both, delivered to the stump of severed axons, results in either the prevention of synaptic stripping when administered immediately after lesion or in a promotion of reinnervation of afferents to abducens motoneurons once synaptic stripping had occurred, in concert with the recovery of synaptic potentials evoked from the vestibular nerve. Synaptotrophic effects, however, were larger when both neurotrophins were applied together. The axotomy-induced reduction in firing sensitivities related to eye movements were also restored to normal values when BDNF and NT-3 were administered, but discharge characteristics recovered in a complementary manner when only one neurotrophin was used. This is the first report to show selective retrograde trophic dependence of circuit-driven firing properties in vivo indicating that NT-3 restored the phasic firing, whereas BDNF supported the tonic firing of motoneurons during eye movement performance. Therefore, our data report a link between the synaptotrophic actions of neurotrophins, retrogradely delivered, and the alterations of neuronal firing patterns during motor behaviors. These trophic actions could be responsible, in part, for synaptic rearrangements that alter circuit stability and synaptic balance during plastic events of the brain.

show abstract

“…In a first set of experiments, we injected either BDNF, or NT-3, or a combination of both neurotrophins, to the distal stumps of sectioned axons, following two different experimental paradigms: in the first one, we administered the neurotrophin immediately following axotomy, to test the maintenance of motoneuron properties; in the second one, we first axotomized motoneurons and then checked whether neurotrophins could revert the effects of the lesion. To prevent lesioned motoneurons to establish contacts with new targets, we developed an administration device for chronic neurotrophin delivery, which allowed controlling the extracellular environment that bathes the axonal stumps [135]. In a second set of experiments, we injected NGF following the same paradigms explained above.…”

Section: Bdnf and Nt-3 Exert Complementary Actions On The Dischargmentioning

confidence: 99%

Functional Diversity of Neurotrophin Actions on the Oculomotor System

Benítez‐Temiño¹,

Carrizosa²,

Morcuende³

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase). In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review, we summarize these evidences and discuss them in the context of other motor systems.

show abstract

A chronically implantable device for the controlled delivery of substances, and stimulation and recording of activity in severed nerves

Cited by 9 publications

References 15 publications

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons

Complementary Actions of BDNF and Neurotrophin-3 on the Firing Patterns and Synaptic Composition of Motoneurons

Functional Diversity of Neurotrophin Actions on the Oculomotor System

Contact Info

Product

Resources

About