RT Journal Article
SR Electronic
T1 Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 697417
DO 10.1101/697417
A1 Kwan Yeop Lee
A1 Stéphanie Ratté
A1 Steven A. Prescott
YR 2019
UL http://biorxiv.org/content/early/2019/07/09/697417.abstract
AB Neuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia – the misperception of light touch as painful – occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.