Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents I-h and I-SK

• 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 (RCs2) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCs2 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 RCs2 constitute an electrophysiologically stereotyped population with a resting membrane potential of -50.5 +/- 0.4mV and an input resistance of 233.1 +/- 11M. We identified a ZD7288-sensitive hyperpolarization-activated cation current (I-h) in all RCs2, contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCs2 to express small calcium-activated potassium currents (I-SK) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCs2 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

interneurons

mouse

nicotinic acetylcholine receptor alpha2

recurrent inhibition

spinal cord

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