Reversal of theta rhythm flow through intact hippocampal circuits

Abstract

Activity flow through the hippocampus is thought to arise exclusively from unidirectional excitatory synaptic signaling from CA3 to CA1 to the subiculum. Theta rhythms are important for hippocampal synchronization during episodic memory processing; thus, it is assumed that theta rhythms follow these excitatory feedforward circuits. To the contrary, we found that theta rhythms generated in the rat subiculum flowed backward to actively modulate spike timing and local network rhythms in CA1 and CA3. This reversed signaling involved GABAergic mechanisms. However, when hippocampal circuits were physically limited to a lamellar slab, CA3 outputs synchronized CA1 and the subiculum using excitatory mechanisms, as predicted by classic hippocampal models. Finally, analysis of in vivo recordings revealed that this reversed theta flow was most prominent during REM sleep. These data demonstrate that communication between CA3, CA1 and the subiculum is not exclusively unidirectional or excitatory and that reversed inhibitory theta signaling also contributes to intrahippocampal synchrony.

Hippocampal Mechanisms for the Segmentation of Space by Goals and Boundaries

“…Early models of the origin of theta posited that hippocampal cells oscillated at theta due to an external pacemaker drive from the medial septum (Petsche et al 1962;Lewis and Shute 1967;Lee et al 1994). It is now clear that theta-like activity can be induced in hippocampal slices (Konopacki et al 1988;Goutagny et al 2009) and that there are multiple theta generators (Buzsáki et al 1986;Kamondi et al 1998) driven by the entorhinal cortex (Mitchell and Ranck 1980;Alonso and Llinás 1989), CA3 (Konopacki et al 1988;Kocsis et al 1999), the subiculum (Jackson et al 2014), and other areas within the hippocampal circuit (Konopacki et al 1988). Even single cells show resonance at theta frequencies (Leung and Yu 1998;Stark et al 2013;Vaidya and Johnston 2013).…”

“…Those subicular cells would integrate across a broad range of hippocampal theta phases (~60 ). In vitro comparisons of physiology in hippocampal slices versus that in an intact preparation showed large differences in the theta phase offsets between CA3 and the subiculum and in the theta frequency, suggesting that the slice preparation severed processes necessary for communication across lamellae (Jackson et al 2014). Physiological studies, like those done between CA3 and CA1 (Andersen et al 2000), are needed to determine the strength of these cross-laminar projections.…”

Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency

“…Single cell properties and local network interactions thus constitute a first level of theta rhythm generation, intrinsic to the hippocampal neuronal network. Accordingly, recent work from our laboratory using the isolated in vitro hippocampus has shown that the hippocampus contains two series of intrinsic oscillators, located longitudinally in the distal CA1/subiculum (dCA1/SUB) and CA3 regions (Goutagny et al, 2009;Jackson et al, 2011;Gu et al, 2013;Jackson et al, 2014). A prominent external excitatory input from the entorhinal cortex (EC) also participates in theta oscillations (Kamondi et al, 1998).…”

Inducing theta oscillations in the entorhinal hippocampal network in vitro

“…These results support the idea that the EC may be the natural theta rhythm generator, but that there may be other regions that can function as potential rhythm generators, or instead that there may be various forms of theta that can be generated by different mechanisms under various conditions. One recent study, indeed, showed that theta rhythms generated in the rat subiculum flowed backward to actively modulate CA1 and CA3 activities in the whole-hippocampus preparation (Jackson et al 2014). …”