Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK

• Published in: The European journal of neuroscience 2015-04, Vol.41 (7), p.889-900
• Main Authors: Perry, Sharn, Gezelius, Henrik, Larhammar, Martin, Hilscher, Markus M., Lamotte d'Incamps, Boris, Leao, Katarina E., Kullander, Klas
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Animals, Newborn; Apamin - pharmacology; interneurons; Ion Channels - metabolism; Lumbar Vertebrae; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons - physiology; mouse; Neurotransmitter Agents - pharmacology; nicotinic acetylcholine receptor alpha2; Pyrimidines - pharmacology; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; recurrent inhibition; Renshaw Cells - drug effects; Renshaw Cells - physiology; RNA, Messenger - metabolism; spinal cord; Spinal Cord - drug effects; Spinal Cord - physiology; Spinal Nerve Roots - physiology; Tissue Distribution
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12852

Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RCsα2) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCsα2 properties confirmed that neurons genetically marked by the Chrna2‐Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole‐cell patch‐clamp recordings revealed that RCsα2 constitute an electrophysiologically stereotyped population with a resting membrane potential of −50.5 ± 0.4 mV and an input resistance of 233.1 ± 11 MΩ. We identified a ZD7288‐sensitive hyperpolarization‐activated cation current (Ih) in all RCsα2, contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCsα2 to express small calcium‐activated potassium currents (ISK) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCsα2 can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role. Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. We here show that expression of the cholinergic nicotinic receptor alpha2 (Chrna2) identifies Renshaw cells in the mouse spinal cord. Recordings of these cells revealed that they constitute an electrophysiologically homogenous population that display currents known to modulate rebound excitation and firing frequency.