Directionality revealed in hippocampal theta sequences
Schematic illustration of sensory-dependent theta sequences. The temporal correlations of spikes within theta cycles describe the immediate trajectory in 2D space. Title:
When animals forage in an environment, they need to remember the sequence of locations along the trajectory, including their past, current and future locations. It was previously proposed that the running trajectory could be represented by hippocampal theta sequences. As the animal traverses across a series of place fields, these place cells fire sequentially within each cycle of background theta oscillation (6-12Hz). Their temporal correlations in theta time scale reflect the visiting order of place fields, and thus, depict the trajectory (see Illustration).
In a new study, neuroscientists from Freiburg and San Diego have discovered that some theta sequences have, however, fixed firing orders regardless of the visiting order of place fields. Contrary to the previous notion that theta sequences represent the immediate running trajectory, these “intrinsic” sequences are fixed location sequence motifs which rather represent the recursive hippocampal connectivity as memories of previous trajectories or even experience-independent prestructure.
The authors further looked to characterize the intrinsic sequences by inspecting their spike phase distributions. As place cells fire sequentially within a theta cycle, the spikes from place fields ahead of the animal will appear at later phases, while those spikes from current or past locations will appear at earlier phases. They found that intrinsic sequences tend to have later spike phases and reflect more the prospective locations that the animals are going to visit, as the place cells at future locations are activated by the pre-existing connectivity before the animals arrive there.
Furthermore, the paper reports that these intrinsic sequences contribute to the directionality of theta sequences. When the place fields are traversed in the opposite of their preferred firing direction and receive the lowest sensorimotor drive, the intrinsic sequences and later spike phases become even more noticeable, as explained by the authors: “There are two types of theta sequences. One is produced by the sensory drive that reflects the trajectory, while the other is by recurrent connectivity which plays out the rigid intrinsic sequences. When the sensory input becomes smaller, the recurrent connectivity dominates and intrinsic sequences become more overt.”. The directionality of theta sequences is thus reflected in a shift of phase distribution and arises from the interplay between sensorimotor and recurrent drive.
Moreover, the authors found that the directional modulations are only visible in the hippocamapal CA3 but not the CA1 region, which, they say, “is consistent with the anatomical evidence that CA3 neurons project more extensive recurrent collaterals to itself and even form a recurrent loop with the dentate gyrus” . The more recurrent structure in CA3 gives rise to its autoassociative capabilities that may store the sequence memory.
The functional roles of these intrinsic sequences are still unclear and up for discussion. One speculation is that such prestructure can help organize the spatial representation in a novel environment, where sensory experience is absent and the prestructure serves as the only prior information for representing the trajectory.
Contact:
Yuk-Hoi Yiu
hoi.yiu@biologie.uni-freiburg.de
Albert-Ludwigs-Universität Freiburg
Fakultät für Biologie & Bernstein Center Freiburg
Prof. Dr. Christian Leibold
christian.leibold@biologie.uni-freiburg.de
Albert-Ludwigs-Universität Freiburg
Fakultät für Biologie & Bernstein Center Freiburg
Reference:
Yiu Y-H, Leutgeb JK, Leibold C (2022) Directional Tuning of Phase Precession Properties in the Hippocampus. The