Dendritic-targeting interneuron controls spike timing of hippocampal CA1 pyramidal neuron via activation of I(h).

Accurate spike timing of hippocampal CA1 pyramidal neurons relative to the on-going theta-frequency network oscillations is important in hippocampal spatial information and memory processing. Accumulating evidence suggests that inhibitory interneurons are important in regulating the activity of pyramidal neurons in the local hippocampal circuit. Interneurons synapse mostly onto the dendrites of CA1 pyramidal neurons where they are believed to take part in dendritic computation. However, it remains unclear how the diverse types of interneurons targeting different dendritic domains of pyramidal neurons differentially contribute to the precise control of spike timing during network oscillation. Here, using a full-morphology multi-compartment model of CA1 pyramidal neuron, we find that phasic inhibitory inputs during theta oscillation can precisely control spike timing of CA1 pyramidal neurons by not only delaying but also advancing the spike times. In addition, we report that the biophysical mechanism underlying the spike time advancement caused by inhibitory input is due to the hyperpolarization-activated mixed cation current (I(h)) in pyramidal neuron dendrites. Thus, a wide variety of interneuron types targeting different dendritic locations of pyramidal neuron activate dendritic I(h) to influence spike timing of pyramidal neuron during theta oscillation. This suggests an important functional role of dendritic-targeting interneurons in hippocampal spike timing-based information processing.