Spontaneous Bursting Activity in the Developing Entorhinal Cortex

Abstract

Periodic spontaneous activity represents an important attribute of the developing nervous system. The entorhinal cortex (EC) is a crucial component of the medial temporal lobe memory system. Yet, little is known about spontaneous activity in the immature EC. Here, we investigated spontaneous field potential (fp) activity and intrinsic firing patterns of medial EC layer III principal neurons in brain slices obtained from rats at the first two postnatal weeks. A fraction of immature layer III neurons spontaneously generated prolonged (2-20 s) voltage-dependent intrinsic bursting activity. Prolonged bursts were dependent on the extracellular concentration of Ca(2+) ([Ca(2+)](o)). Thus, reduction of [Ca(2+)](o) increased the fraction of neurons with prolonged bursting by inducing intrinsic bursts in regularly firing neurons. In 1 mm [Ca(2+)](o), the percentages of neurons showing prolonged bursts were 53%, 81%, and 29% at postnatal day 5 (P5)-P7, P8-P10, and P11-P13, respectively. Prolonged intrinsic bursting activity was blocked by buffering intracellular Ca(2+) with BAPTA, and by Cd(2+), flufenamic acid (FFA), or TTX, and was suppressed by nifedipine and riluzole, suggesting that the Ca(2+)-sensitive nonspecific cationic current (I(CAN)) and the persistent Na(+) current (I(Nap)) underlie this effect. Indeed, a 0.2-1 s suprathreshold current step stimulus elicited a terminated plateau potential in these neurons. fp recordings at P5-P7 showed periodic spontaneous glutamate receptor-mediated events (sharp fp events or prolonged fp bursts) which were blocked by FFA. Slow-wave network oscillations become a dominant pattern at P11-P13. We conclude that prolonged intrinsic bursting activity is a characteristic feature of developing medial EC layer III neurons that might be involved in neuronal and network maturation.