Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex
Progress toward developing effective prophylaxis and treatment of posttraumatic epilepsy depends on a detailed understanding of the basic underlying mechanisms. One important factor contributing to epileptogenesis is decreased efficacy of GABAergic inhibition. Here we tested the hypothesis that the...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-07-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112001118 |
| _version_ | 1818827326535761920 |
|---|---|
| author | Yunyong Ma David A. Prince |
| author_facet | Yunyong Ma David A. Prince |
| author_sort | Yunyong Ma |
| collection | DOAJ |
| description | Progress toward developing effective prophylaxis and treatment of posttraumatic epilepsy depends on a detailed understanding of the basic underlying mechanisms. One important factor contributing to epileptogenesis is decreased efficacy of GABAergic inhibition. Here we tested the hypothesis that the output of neocortical fast-spiking (FS) interneurons onto postsynaptic targets would be decreased in the undercut (UC) model of chronic posttraumatic epileptogenesis. Using dual whole-cell recordings in layer IV barrel cortex, we found a marked increase in the failure rate and a very large reduction in the amplitude of unitary inhibitory postsynaptic currents (uIPSCs) from FS cells to excitatory regular spiking (RS) neurons and neighboring FS cells. Assessment of the paired pulse ratio and presumed quantal release showed that there was a significant, but relatively modest, decrease in synaptic release probability and a non-significant reduction in quantal size. A reduced density of boutons on axons of biocytin-filled UC FS cells, together with a higher coefficient of variation of uIPSC amplitude in RS cells, suggested that the number of functional synapses presynaptically formed by FS cells may be reduced. Given the marked reduction in synaptic strength, other defects in the presynaptic vesicle release machinery likely occur, as well. |
| first_indexed | 2024-12-19T00:41:47Z |
| format | Article |
| id | doaj.art-ff3c84a78c254571978fbce8db51d164 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T00:41:47Z |
| publishDate | 2012-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ff3c84a78c254571978fbce8db51d1642022-12-21T20:44:30ZengElsevierNeurobiology of Disease1095-953X2012-07-01471102113Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortexYunyong Ma0David A. Prince1Dept. of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USACorresponding author at: Dept. of Neurology and Neurological Sciences, Stanford University, Room M016, Alway Building, 300 Pasteur Drive, Stanford, CA 94305-5122, USA. Fax: +1 650 723 1080.; Dept. of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USAProgress toward developing effective prophylaxis and treatment of posttraumatic epilepsy depends on a detailed understanding of the basic underlying mechanisms. One important factor contributing to epileptogenesis is decreased efficacy of GABAergic inhibition. Here we tested the hypothesis that the output of neocortical fast-spiking (FS) interneurons onto postsynaptic targets would be decreased in the undercut (UC) model of chronic posttraumatic epileptogenesis. Using dual whole-cell recordings in layer IV barrel cortex, we found a marked increase in the failure rate and a very large reduction in the amplitude of unitary inhibitory postsynaptic currents (uIPSCs) from FS cells to excitatory regular spiking (RS) neurons and neighboring FS cells. Assessment of the paired pulse ratio and presumed quantal release showed that there was a significant, but relatively modest, decrease in synaptic release probability and a non-significant reduction in quantal size. A reduced density of boutons on axons of biocytin-filled UC FS cells, together with a higher coefficient of variation of uIPSC amplitude in RS cells, suggested that the number of functional synapses presynaptically formed by FS cells may be reduced. Given the marked reduction in synaptic strength, other defects in the presynaptic vesicle release machinery likely occur, as well.http://www.sciencedirect.com/science/article/pii/S0969996112001118InhibitionPaired recordingsBarrelFast-spikingEpilepsy |
| spellingShingle | Yunyong Ma David A. Prince Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex Neurobiology of Disease Inhibition Paired recordings Barrel Fast-spiking Epilepsy |
| title | Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex |
| title_full | Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex |
| title_fullStr | Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex |
| title_full_unstemmed | Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex |
| title_short | Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex |
| title_sort | functional alterations in gabaergic fast spiking interneurons in chronically injured epileptogenic neocortex |
| topic | Inhibition Paired recordings Barrel Fast-spiking Epilepsy |
| url | http://www.sciencedirect.com/science/article/pii/S0969996112001118 |
| work_keys_str_mv | AT yunyongma functionalalterationsingabaergicfastspikinginterneuronsinchronicallyinjuredepileptogenicneocortex AT davidaprince functionalalterationsingabaergicfastspikinginterneuronsinchronicallyinjuredepileptogenicneocortex |