Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

Carlos Bernardo Mantilla, Jeffrey P. Bailey, Wen Zhi Zhan, Gary C Sieck

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Following cervical spinal cord injury at C 2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalExperimental Neurology
Volume234
Issue number1
DOIs
StatePublished - Mar 2012

Fingerprint

Motor Neurons
Diaphragm
Spinal Cord Injuries
Neurotransmitter Receptor
Neuronal Plasticity
Laser Capture Microdissection
N-Methylaspartate
Cervical Cord
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Cholera Toxin
Frozen Sections
Real-Time Polymerase Chain Reaction
Spinal Cord
Pharmacology
Messenger RNA
Injections

Keywords

  • 5-HTR2a
  • AMPA
  • Laser capture microdissection
  • Motor neuron
  • Neuroplasticity
  • Neurotransmitter
  • NMDA
  • Quantitative real-time RT-PCR
  • Spinal hemisection

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury. / Mantilla, Carlos Bernardo; Bailey, Jeffrey P.; Zhan, Wen Zhi; Sieck, Gary C.

In: Experimental Neurology, Vol. 234, No. 1, 03.2012, p. 191-199.

Research output: Contribution to journalArticle

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