The hippocampal theta rhythm observed in humans, primates, and rodents, is thought to play an important role in memory encoding and retrieval as demonstrated in numerous concurrent recording studies during memory tasks. It has been difficult, however, to demonstrate this rhythm in ex vivo slice preparations, possibly because the generator for the rhythm lies outside of the hippocampus, perhaps from cholinergic input from the septal nuclei. Goutagny et al (Goutagny R, Jackson J, Williams S. Self-generated theta oscillations in the hippocampus.Nat Neurosci. 2009;12(12):1491–1493) now present data supporting the intrinsic generation of the theta rhythm in intact hippocampal specimens which have not been sliced. This rhythmic activity appears to arise in the CA1 hippocampal subfield, and arises from the longitudinal (septal-temporal axis) coupling of multiple independent rhythmic generators.
The spontaneous theta activity persisted for up to 2 hours, and showed a sink-source alteration as a function of depth into CA1, with the pyramidal cell layer acting as a sink, and the stratum radiatum (region of pyramidal cell dendritic field) acting as source. Interestingly, a complete 180° phase reversal of the waveform as a function of depth also occurs over a distance of approximately 150 μm. This activity could not be blocked with the application of a muscarinic blocker, implying the lack of necessity of the cholinergic input to the hippocampus for its production.
Goutagny et al also measured the theta waveform coherence longitudinally along the septal-temporal axis and transversely into the other hippocampal subfields. Coherence was preserved longitudinally, but not transversely, with the lowest coherence occuring in CA3 (Fig. 1). CA1 was even able to support the theta activity in an isolated preparation without CA3, with no change in observed oscillation frequency. The authors also demonstrate that it is possible to decouple local oscillators longitudinally along CA1. They used a procaine solution applied locally at a discrete location along CA1, and then measured the theta coherence proximal and distal to the blockade. The theta oscillation systems proved to be uncoupled, with the septal system leading the temporal side. This implies a series of independent but coupled oscillating systems arranged longitudinally along CA1.
(A) Coherence of theta waveform recorded from intact ex vivo hippocampal specimen demonstrating the strong longitudinal (temporal–septal) coherence, and the rapid decay in transverse (CA1-CA3) coherence. (C), application of procaine (sodium channel blockade) reveals loss of entrainment (“post” data) in the theta waveform activity measured between 2 points along the longitudinal axis of the hippocampal preparation.
(A) Coherence of theta waveform recorded from intact ex vivo hippocampal specimen demonstrating the strong longitudinal (temporal–septal) coherence, and the rapid decay in transverse (CA1-CA3) coherence. (C), application of procaine (sodium channel blockade) reveals loss of entrainment (“post” data) in the theta waveform activity measured between 2 points along the longitudinal axis of the hippocampal preparation.
And finally, Goutagny et al also explored the theta waveform generation at the cellular level, demonstrating the entrainment of individual pyramidal cells and interneurons in CA1 with the gross extracellular field potential oscillation. The pyramidal cells appear to be driven primarily by rhythmic IPSPs from interneurons, and exhibit rebound spiking behavior after the IPSP. Similarly, the inhibitory cells receive phase EPSPs which are phase locked to the theta oscillation, implying a feedback loop between the principal cells and inhibitory cells which gives rise to the spontaneous oscillation. For a neurosurgeon, these details are relevant, not only for understanding the basic physiology of memory and the hippocampus, but could also influence the design of future stimulation systems designed to interact with these regions for the control of seizures or conceivably for the improvement of memory.
