Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model

Hanna Wootz, Eileen Fitzsimons-Kantamneni, Martin Larhammar, Travis M. Rotterman, Anders Enjin, Kalicharan Patra, Elodie André, Brigitte Van Zundert, Klas Kullander, Francisco J. Alvarez

Resultado de la investigación: Article

33 Citas (Scopus)

Resumen

Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin-related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing.

Idioma originalEnglish
Páginas (desde-hasta)1449-1469
Número de páginas21
PublicaciónJournal of Comparative Neurology
Volumen521
N.º7
DOI
EstadoPublished - 1 may 2013

Huella dactilar

Motor Neurons
Amyotrophic Lateral Sclerosis
Nicotinic Receptors
Cholinergic Receptors
Calbindins
Down-Regulation
Calcitonin
Synapses
Axons
Renshaw Cells
Disease Progression
Cell Survival
Spinal Cord
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)

Citar esto

Wootz, H., Fitzsimons-Kantamneni, E., Larhammar, M., Rotterman, T. M., Enjin, A., Patra, K., ... Alvarez, F. J. (2013). Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model. Journal of Comparative Neurology, 521(7), 1449-1469. https://doi.org/10.1002/cne.23266
Wootz, Hanna ; Fitzsimons-Kantamneni, Eileen ; Larhammar, Martin ; Rotterman, Travis M. ; Enjin, Anders ; Patra, Kalicharan ; André, Elodie ; Van Zundert, Brigitte ; Kullander, Klas ; Alvarez, Francisco J. / Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model. En: Journal of Comparative Neurology. 2013 ; Vol. 521, N.º 7. pp. 1449-1469.
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abstract = "Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin-related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing.",
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Wootz, H, Fitzsimons-Kantamneni, E, Larhammar, M, Rotterman, TM, Enjin, A, Patra, K, André, E, Van Zundert, B, Kullander, K & Alvarez, FJ 2013, 'Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model', Journal of Comparative Neurology, vol. 521, n.º 7, pp. 1449-1469. https://doi.org/10.1002/cne.23266

Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model. / Wootz, Hanna; Fitzsimons-Kantamneni, Eileen; Larhammar, Martin; Rotterman, Travis M.; Enjin, Anders; Patra, Kalicharan; André, Elodie; Van Zundert, Brigitte; Kullander, Klas; Alvarez, Francisco J.

En: Journal of Comparative Neurology, Vol. 521, N.º 7, 01.05.2013, p. 1449-1469.

Resultado de la investigación: Article

TY - JOUR

T1 - Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model

AU - Wootz, Hanna

AU - Fitzsimons-Kantamneni, Eileen

AU - Larhammar, Martin

AU - Rotterman, Travis M.

AU - Enjin, Anders

AU - Patra, Kalicharan

AU - André, Elodie

AU - Van Zundert, Brigitte

AU - Kullander, Klas

AU - Alvarez, Francisco J.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin-related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing.

AB - Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and cholinergic nicotinic receptor subunit alpha2 [Chrna2]), two general markers for motor neurons (NeuN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondrolectin and calcitonin-related polypeptide alpha [Calca]), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in diminished control of motor neuron firing.

KW - Amyotrophic lateral sclerosis

KW - Recurrent inhibition

KW - Synapses

KW - VAChT

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JF - Journal of Comparative Neurology

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Wootz H, Fitzsimons-Kantamneni E, Larhammar M, Rotterman TM, Enjin A, Patra K y otros. Alterations in the motor neuron-renshaw cell circuit in the Sod1G93A mouse model. Journal of Comparative Neurology. 2013 may 1;521(7):1449-1469. https://doi.org/10.1002/cne.23266