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Functional integration of new hippocampal neurons following insults to the adult brain is determined by characteristics of pathological environment.

Wood, James LU ; Jackson, Johanna LU ; Jakubs, Katherine; Chapman, Katie LU ; Ekdahl Clementson, Christine LU ; Kokaia, Zaal LU ; Kokaia, Merab LU and Lindvall, Olle LU (2011) In Experimental Neurology 229(2). p.484-493
Abstract
We have previously shown that following severe brain insults, chronic inflammation induced by lipopolysaccharide (LPS) injection, and status epilepticus, new dentate granule cells exhibit changes of excitatory and inhibitory synaptic drive indicating that they may mitigate the abnormal brain function. Major inflammatory changes in the environment encountering the new neurons were a common feature of these insults. Here, we have asked how the morphology and electrophysiology of new neurons are affected by a comparably mild pathology: repetitive seizures causing hyperexcitability but not inflammation. Rats were subjected to rapid kindling, i.e., 40 rapidly recurring, electrically-induced seizures, and subsequently exposed to stimulus-evoked... (More)
We have previously shown that following severe brain insults, chronic inflammation induced by lipopolysaccharide (LPS) injection, and status epilepticus, new dentate granule cells exhibit changes of excitatory and inhibitory synaptic drive indicating that they may mitigate the abnormal brain function. Major inflammatory changes in the environment encountering the new neurons were a common feature of these insults. Here, we have asked how the morphology and electrophysiology of new neurons are affected by a comparably mild pathology: repetitive seizures causing hyperexcitability but not inflammation. Rats were subjected to rapid kindling, i.e., 40 rapidly recurring, electrically-induced seizures, and subsequently exposed to stimulus-evoked seizures twice weekly. New granule cells were labeled 1week after the initial insult with a retroviral vector encoding green fluorescent protein. After 6-8weeks, new neurons were analyzed using confocal microscopy and whole-cell patch-clamp recordings. The new neurons exposed to the pathological environment exhibited only subtle changes in their location, orientation, dendritic arborizations, and spine morphology. In contrast to the more severe insults, the new neurons exposed to rapid kindling and stimulus-evoked seizures exhibited enhanced afferent excitatory synaptic drive which could suggest that the cells that had developed in this environment contributed to hyperexcitability. However, the new neurons showed concomitant reduction of intrinsic excitability which may counteract the propagation of this excitability to the target cells. This study provides further evidence that following insults to the adult brain, the pattern of synaptic alterations at afferent inputs to newly generated neurons is dependent on the characteristics of the pathological environment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
229
issue
2
pages
484 - 493
publisher
Academic Press
external identifiers
  • wos:000291419400033
  • pmid:21459089
  • scopus:79952599565
ISSN
0014-4886
DOI
10.1016/j.expneurol.2011.03.019
language
English
LU publication?
yes
id
78a28a99-776a-4c50-97ac-5a293a276825 (old id 1937588)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21459089?dopt=Abstract
date added to LUP
2011-05-02 09:26:04
date last changed
2017-11-05 03:25:39
@article{78a28a99-776a-4c50-97ac-5a293a276825,
  abstract     = {We have previously shown that following severe brain insults, chronic inflammation induced by lipopolysaccharide (LPS) injection, and status epilepticus, new dentate granule cells exhibit changes of excitatory and inhibitory synaptic drive indicating that they may mitigate the abnormal brain function. Major inflammatory changes in the environment encountering the new neurons were a common feature of these insults. Here, we have asked how the morphology and electrophysiology of new neurons are affected by a comparably mild pathology: repetitive seizures causing hyperexcitability but not inflammation. Rats were subjected to rapid kindling, i.e., 40 rapidly recurring, electrically-induced seizures, and subsequently exposed to stimulus-evoked seizures twice weekly. New granule cells were labeled 1week after the initial insult with a retroviral vector encoding green fluorescent protein. After 6-8weeks, new neurons were analyzed using confocal microscopy and whole-cell patch-clamp recordings. The new neurons exposed to the pathological environment exhibited only subtle changes in their location, orientation, dendritic arborizations, and spine morphology. In contrast to the more severe insults, the new neurons exposed to rapid kindling and stimulus-evoked seizures exhibited enhanced afferent excitatory synaptic drive which could suggest that the cells that had developed in this environment contributed to hyperexcitability. However, the new neurons showed concomitant reduction of intrinsic excitability which may counteract the propagation of this excitability to the target cells. This study provides further evidence that following insults to the adult brain, the pattern of synaptic alterations at afferent inputs to newly generated neurons is dependent on the characteristics of the pathological environment.},
  author       = {Wood, James and Jackson, Johanna and Jakubs, Katherine and Chapman, Katie and Ekdahl Clementson, Christine and Kokaia, Zaal and Kokaia, Merab and Lindvall, Olle},
  issn         = {0014-4886},
  language     = {eng},
  number       = {2},
  pages        = {484--493},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Functional integration of new hippocampal neurons following insults to the adult brain is determined by characteristics of pathological environment.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2011.03.019},
  volume       = {229},
  year         = {2011},
}