Marcelin Béatrice, Chauvière Laëtitia, Becker Albert, Migliore Michele, Esclapez Monique, Bernard Christophe
INSERM-U751, Université de la Méditerranée, 27, Bd Jean Moulin, 13005 Marseille, France.
Neurobiol Dis. 2009 Mar;33(3):436-47. doi: 10.1016/j.nbd.2008.11.019. Epub 2008 Dec 16.
I(h) tunes hippocampal CA1 pyramidal cell dendrites to optimally respond to theta inputs (4-12 Hz), and provides a negative time delay to theta inputs. Decreased I(h) activity, as seen in experimental temporal lobe epilepsy (TLE), could significantly alter the response of dendrites to theta inputs. Here we report a progressive erosion of theta resonance and phase lead in pyramidal cell dendrites during epileptogenesis in a rat model of TLE. These alterations were due to decreased I(h) availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. This acquired HCN channelopathy thus compromises temporal coding and tuning to theta inputs in pyramidal cell dendrites. Decreased theta resonance in vitro also correlated with a reduction in theta frequency and power in vivo. We suggest that the neuronal/circuitry changes associated with TLE, including altered I(h)-dependent inductive mechanisms, can disrupt hippocampal theta function.
I(h)调节海马CA1锥体细胞树突，以最佳方式响应θ输入（4 - 12赫兹），并为θ输入提供负时间延迟。如在实验性颞叶癫痫（TLE）中所见，I(h)活性降低会显著改变树突对θ输入的反应。在此我们报告，在TLE大鼠模型的癫痫发生过程中，锥体细胞树突的θ共振和相位超前出现渐进性减弱。这些改变是由于I(h)可用性降低，这是通过HCN1/HCN2亚基表达下降导致h电流减少，以及残余通道动力学改变所致。这种获得性HCN通道病因此损害了锥体细胞树突对θ输入的时间编码和调节。体外θ共振降低也与体内θ频率和功率降低相关。我们认为，与TLE相关的神经元/回路变化，包括改变的I(h)依赖性诱导机制，可破坏海马θ功能。
