Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn
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. Disinh...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/49753 |
| _version_ | 1811236808482095104 |
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| author | Kwan Yeop Lee Stéphanie Ratté Steven A Prescott |
| author_facet | Kwan Yeop Lee Stéphanie Ratté Steven A Prescott |
| author_sort | Kwan Yeop Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:14:29Z |
| format | Article |
| id | doaj.art-577289e40ca24aff8e5bd09d2db49657 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:14:29Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-577289e40ca24aff8e5bd09d2db496572022-12-22T03:33:28ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.49753Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal hornKwan Yeop Lee0Stéphanie Ratté1Steven A Prescott2https://orcid.org/0000-0002-3827-4512Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, CanadaNeurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, CanadaNeurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, CanadaNeuropathic 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.https://elifesciences.org/articles/49753allodynianeuropathic paindisinhibitionspinal cordKCC2spatial summation |
| spellingShingle | Kwan Yeop Lee Stéphanie Ratté Steven A Prescott Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn eLife allodynia neuropathic pain disinhibition spinal cord KCC2 spatial summation |
| title | Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| title_full | Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| title_fullStr | Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| title_full_unstemmed | Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| title_short | Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| title_sort | excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn |
| topic | allodynia neuropathic pain disinhibition spinal cord KCC2 spatial summation |
| url | https://elifesciences.org/articles/49753 |
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