RT Journal Article
SR Electronic
T1 Stroke Accelerates and Uncouples Intrinsic and Synaptic Excitability Maturation of Mouse Hippocampal DCX<sup>+</sup> Adult-Born Granule Cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1755
OP 1766
DO 10.1523/JNEUROSCI.3303-17.2018
VO 39
IS 9
A1 Mihai Ceanga
A1 Silke Keiner
A1 Benedikt Grünewald
A1 Holger Haselmann
A1 Christiane Frahm
A1 Sebastien Couillard-Després
A1 Otto W. Witte
A1 Christoph Redecker
A1 Christian Geis
A1 Albrecht Kunze
YR 2019
UL http://www.jneurosci.org/content/39/9/1755.abstract
AB Stroke robustly stimulates adult neurogenesis in the hippocampal dentate gyrus. It is currently unknown whether this process induces beneficial or maladaptive effects, but morphological and behavioral studies have reported aberrant neurogenesis and impaired hippocampal-dependent memory following stroke. However, the intrinsic function and network incorporation of adult-born granule cells (ABGCs) after ischemia is unclear. Using patch-clamp electrophysiology, we evaluated doublecortin-positive (DCX+) ABGCs as well as DCX− dentate gyrus granule cells 2 weeks after a stroke or sham operation in DCX/DsRed transgenic mice of either sex. The developmental status, intrinsic excitability, and synaptic excitability of ABGCs were accelerated following stroke, while dendritic morphology was not aberrant. Regression analysis revealed uncoupled development of intrinsic and network excitability, resulting in young, intrinsically hyperexcitable ABGCs receiving disproportionately large glutamatergic inputs. This aberrant functional maturation in the subgroup of ABGCs in the hippocampus may contribute to defective hippocampal function and increased seizure susceptibility following stroke.SIGNIFICANCE STATEMENT Stroke increases hippocampal neurogenesis but the functional consequences of the postlesional response is mostly unclear. Our findings provide novel evidence of aberrant functional maturation of newly generated neurons following stroke. We demonstrate that stroke not only causes an accelerated maturation of the intrinsic and synaptic parameters of doublecortin-positive, new granule cells in the hippocampus, but that this accelerated development does not follow physiological dynamics due to uncoupled intrinsic and synaptic maturation. Hyperexcitable immature neurons may contribute to disrupted network integration following stroke.