Inducing theta oscillations in the entorhinal hippocampal network in vitro.

The hippocampal theta rhythm emerges as rhythmic and synchronized activities among the hippocampus and hippocampus-associated brain regions during active exploration, providing a potential means for inter-regional communication. However, after decades of research, the origins of the theta rhythm remain elusive, at least partly due to the difficulty in recording from all three essential regions for theta generation, namely the hippocampus itself, the septum, and the entorhinal cortex. For this reason, we established an in vitro theta model in a septo-entorhinal-hippocampal brain slice tri-culture system by pairing septal cholinergic inputs with hippocampal local activities. Our study shows that the local entorhinal cortical circuit may play an active and critical role in hippocampal theta rhythm generation. Our study also reveals a potential mechanism for theta rhythms to emerge as the functional results of dynamic interactions among the septum, hippocampus, and the entorhinal cortex, in the absence of clear pace makers.