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Sunday July 6, 2025 17:20 - 19:20 CEST
P063 Dichotomous Dynamics of Hippocampal and Lateral Septum Oscillations: State-Dependent Topology and Directional Causality During Sleep and Wakefulness

Amir Khani1,Nima Dehghani1,2*

1 N3HUB Initiative, Massachusetts Institute for Technology, Cambridge, U.S.A.
2McGovern Institute for Brain Research, Massachusetts Institute for Technology, Cambridge, U.S.A.


*Email: nima.dehghani@mit.edu

Introduction

Sharp-wave ripples (SWRs) in the hippocampus (HPC) and high-frequency oscillations (HFOs) in the lateral septum (LS) play critical roles in memory consolidation and information routing to subcortical areas. However, the precise spatiotemporal dynamics and causal relationships between these oscillations remain poorly understood. Using multiple analytical approaches, we explored the coordination of HPC-SWR and LS-HFO oscillations during Non-Rapid Eye Movement (NREM) sleep and wakefulness, focusing on their topological features, causal relationships, and dimensional properties.
Methods
We analyzed publicly available LFP recordings from hippocampal subfields and the lateral septum in freely behaving rats [1]. To identify oscillations, we detected ripples following the methods described in [1]. To assess temporal coordination, we employed conditional probability analysis to quantify ripple co-occurrence between regions. To characterize oscillation structure, we applied Topological Data Analysis (TDA) using time-delay embedding (dimension = 3, delay = 2). To determine directional influences, we implemented Convergent Cross Mapping (CCM) for causality assessment [2]. To evaluate the dimensionality of neural activity, we utilized Principal Component Analysis (PCA) across individual channels, regions, and brain states [3].
Results
HPC ripples consistently preceded LS ripples, with the conditional probability of LS ripples given HPC-SWR, P(LS|HPC), higher than the probability of HPC-SWR given LS ripples, P(HPC|LS), especially during NREM sleep (Fig.1E). TDA revealed distinct topological structures: LS HFOs showed state-dependent complexity differences between sleep and awake, while HPC ripples maintained similar features across states (Fig.1D). Bidirectional causality analysis showed LS-HFOs influenced HPC-SWRs more than the reverse across both states, with a stronger relationship during NREM sleep (Fig.1C). Dimensionality analysis, examining SWR events across epochs/channels and applying PCA, highlighted the variability and complexity of SWRs in HPC compared to more uniform LS HFOs (Fig.1A,F).
Discussion
Our findings reveal a complex, bidirectional relationship between HPC and LS during ripple events, with stronger coupling during NREM sleep. The higher intrinsic dimensionality of HPC activity during SWRs reflects its role in complex memory processes, while the lower-dimensional LS activity suggests a streamlined relay function [1]. These results align with prior evidence showing LS neuron activation by hippocampal SWRs [1] and highlight state-dependent coordination between HPC and LS. State-dependent coordination changes suggest that during NREM sleep, the coordination supports memory consolidation, while during wakefulness, it facilitates spatial navigation and behavior.



Figure 1. (A) PCA dimensionality of HPC/LS ripples during NREM sleep (left) and wakefulness (right). (B) Raw LFP traces of HPC-SWR (top) and LS-HFO (bottom). (C) Bidirectional CCM analysis: NREM (top) and wakefulness (bottom). (D) Topological features during NREM: H1 count (left) and Shannon entropy (right). (E) Ripple co-occurrence probability: NREM (left) and wakefulness (right). (F) Channel-wise PCA dime
Acknowledgements
N.D. is supported by NIH Grant R24MH117295.The authors wish to thank NIH for its sponsorship of DANDI archive (DANDI: Distributed Archives for Neurophysiology Data Integration), which provided the open-access data used in this study.
References
[1] Tingley, D., Buzsaki, G. (2020). Routing of hippocampal ripples to subcortical structures via the
lateral septum. Neuron, 105(1), 138-149.e5.
[2] Sugihara, G., et al (2012). Detecting
causality in complex ecosystems. Science, 338(6106), 496–500.
[3] Dehghani, N., et al (2010). Magnetoencephalography
demonstrates multiple asynchronous generators during human sleep spindles. Journal of
Neurophysiology, 104(1), 179-188.
[4] Tingley, D., Buzsaki, G. (2018). Transformation of a spatial map across the hippocampal-lateral septal
circuit. Neuron, 98(6), 1229-1242.e5.
Sunday July 6, 2025 17:20 - 19:20 CEST
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