Burton Brian G, Economo Michael N, Lee G Jenny, White John A
Department of Biomedical Engineering, Center for Memory and Brain, Center for BioDynamics, Boston University, Boston, Massachusetts, USA.
J Neurophysiol. 2008 Dec;100(6):3144-57. doi: 10.1152/jn.90424.2008. Epub 2008 Oct 1.
Mature stellate cells of the rat medial entorhinal cortex (EC), layer II, exhibit subthreshold membrane potential oscillations (MPOs) at theta frequencies (4-12 Hz) in vitro. We find that MPOs appear between postnatal days 14 (P14) and 18 (P18) but show little further change by day 28+ (P28-P32). To identify the factors responsible, we examined the electrical responses of developing stellate cells, paying attention to two currents thought necessary for mature oscillation: the h current I(h), which provides the slow rectification required for resonance; and a persistent sodium current I(NaP), which provides amplification of resonance. Responses to injected current revealed that P14 cells were often nonresonant with a relatively high resistance. Densities of I(h) and I(NaP) both rose by about 50% from P14 to P18. However, I(h) levels fell to intermediate values by P28+. Given the nonrobust trend in I(h) expression and a previously demonstrated potency of even low levels of I(h) to sustain oscillation, we propose that resonance and MPOs are limited at P14 more by low levels of I(NaP) than of I(h). The relative importance of I(NaP) for the development of MPOs is supported by simulations of a conductance-based model, which also suggest that general shunt conductance may influence the precise age when MPOs appear. In addition to our physiological study, we analyzed spine densities at P14, P18, and P28+ and found a vigorous synaptogenesis across the whole period. Our data predict that functions that rely on theta rhythmicity in the hippocampal network are limited until at least P18.
大鼠内嗅皮层(EC)第II层的成熟星状细胞在体外会在θ频率(4 - 12赫兹)下表现出阈下膜电位振荡(MPO)。我们发现MPO在出生后第14天(P14)至第18天(P18)之间出现,但到28天以上(P28 - P32)时变化不大。为了确定其成因,我们研究了发育中星状细胞的电反应,关注两种成熟振荡所需的电流:h电流I(h),它提供共振所需的缓慢整流;以及持续性钠电流I(NaP),它提供共振放大。对注入电流的反应表明,P14细胞通常不发生共振且电阻相对较高。从P14到P18,I(h)和I(NaP)的密度均上升了约50%。然而,到P28 +时,I(h)水平降至中间值。鉴于I(h)表达的趋势不明显,且先前已证明即使低水平的I(h)也有维持振荡的能力,我们认为在P14时,共振和MPO受I(NaP)低水平的限制比I(h)更大。基于电导模型的模拟支持了I(NaP)对MPO发育的相对重要性,该模拟还表明一般的分流电导可能会影响MPO出现的精确年龄。除了我们的生理学研究,我们还分析了P14、P18和P28 +时的棘突密度,发现在整个时期都有活跃的突触形成。我们的数据预测,海马网络中依赖θ节律性的功能至少在P18之前是受限的。