Development of theta rhythmicity in entorhinal stellate cells of the juvenile rat.

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.