Intrinsic and synaptic mechanisms determining the timing of neuron population activity during hippocampal theta...

Hippocampal theta (3-8 Hz) is a major electrophysiological activity in rodents, which can be found in primates and humans as well. During theta activity, pyramidal cells and different classes of interneurons were shown to discharge at different phases of the extracellular theta. A recent in vitro study has shown that theta-frequency oscillation can be elicited in a hippocampal CA1 slice by the activation of metabotropic glutamate receptors with similar pharmacological and physiological profile that was found in vivo. We constructed a conductance based three-population network model of the hippocampal CA1 region to study the specific roles of neuron types in the generation of the in vitro theta oscillation and the emergent network properties. Interactions between pairs of neuron populations were studied systematically to assess synchronization and delay properties. We showed that the circuitry consisting of pyramidal cells and two types of hippocampal interneurons [basket and oriens lacunosum-moleculare (O-LM) neurons] was able to generate coherent theta-frequency population oscillation. Furthermore, we found that hyperpolarization-activated nonspecific cation current in pyramidal cells, but not in O-LM neurons, plays an important role in the timing of spike generation, and thus synchronization of pyramidal cells. The model was shown to exhibit the same phase differences between neuron population activities found in vivo, supporting the idea that these patterns of activity are determined internal to the hippocampus.