Postnatal development of inhibition associated with entorhinal cortex input to the CA1 hippocampus

During early development, temporoammonic (TA) input from the entorhinal cortex provides major excitatory drive to the CA1 hippocampus, yet whether this excitation is balanced by feedforward inhibition remains unclear. Using whole-cell recordings from CA1 pyramidal cells (PCs) in intact hippocampi, we found that TA stimulation reliably evoked monosynaptic excitatory postsynaptic currents (EPSCs) from birth, whereas inhibitory postsynaptic currents (IPSCs) were frequently absent or severely delayed during the first postnatal week. The delay between evoked EPSCs and IPSCs shortened with age, narrowing the temporal integration window. Similar dynamics occurred during early sharp waves in vivo, where IPSC bursts followed EPSC bursts by tens of milliseconds, with this delay decreasing over development. Using paired recordings from fast-spiking interneurons (FS-INs) and PCs, we identified two mechanisms underlying delayed feedforward inhibition during the first postnatal week: (i) low FS-IN→PC connectivity, and (ii) a weak monosynaptic entorhinal cortex (EC) drive to FS-INs. By the end of the second week, EC inputs to FS-INs surpassed those to PCs. Together, these findings reveal that feedforward inhibition in the EC-CA1 circuit is delayed, creating a broad temporal window for synaptic integration during the neonatal period. We propose that this extended window supports global bursting, with progressive inhibition maturation contributing to the switch toward sparse coding. KEY POINTS: Feedforward inhibition upon entorhinal input is developmentally delayed, creating a broad temporal integration window in the neonatal CA1 hippocampus. Weak entorhinal drive to CA1 fast-spiking interneurons is the primary cause of delayed feedforward inhibition in neonates. Delayed inhibition is a consistent feature of CA1 early sharp waves in vivo. Maturation of feedforward inhibition may drive the switch from global 'bursting' to sparse coding.