Coordination of hippocampal input and output pathways during sleep-like states

• Author / Creator

  Whitten, Tara A.

• Hippocampal activity is characterized by two state-dependent, mutually exclusive large-amplitude oscillations: theta (3-12 Hz) and the hippocampal slow oscillation (SO; ~1 Hz). These two rhythms have been implicated in different stages of memory processing. Theta occurs during awake exploratory behaviour and REM sleep, while the hippocampal SO occurs during nonREM sleep and is coordinated with the neocortical SO. Coordination between the neocortex and the hippocampus during the SO is of particular importance because this state has been implicated in sleep-dependent consolidation of hippocampal-dependent memories, and this process likely involves bidirectional communication between these two brain structures. The overall goal of this thesis was to understand how hippocampal input and output pathways are coordinated with neocortical activity during the SO, and to compare hippocampal network patterns during SO and theta oscillations. To approach this question, I used urethane anaesthesia as a model for the activity patterns seen during natural sleep. In Chapter 2, I present independent component analysis (ICA) as a method to separate the contributions of distinct hippocampal afferent pathways to the local field potential (LFP) recorded in the dorsal hippocampus, and to assess its reliability across different algorithms, epochs and animals. Five components that were consistent across animals were found which likely correspond to the major afferent pathways to the dorsal hippocampus, in addition to a component representing a volume conducted signal from the neocortex. Two potential applications of the ICA approach are discussed, including the removal of artifacts such as the volume conducted portion of the signal, and the detection of oscillatory activity in separated components using a modification of the Better Oscillation (BOSC) detection method. In Chapter 3, I describe oscillatory activity patterns in the major hippocampal input and output pathways during SO and theta states. During theta, gamma frequency (20-100 Hz) synaptic inputs arriving at CA1 at stratum lacunosum moleculare (SLM) and stratum radiatum (SRad) occur at opposite phases of the theta cycle. During the SO, we found that the gamma-frequency inputs at these layers also arrive at opposite phases with respect to the neocortical SO cycle. Interestingly, we found that synaptic inputs to SLM periodically skip cycles with respect to the neocortical SO, and that this skipping of cycles results in a slowing of the hippocampal SO compared to the neocortical SO. Finally, we found that sharp wave-ripples (SPW-Rs), an activity pattern that has been implicated in the reactivation of firing sequences that might underlie memory consolidation, can occur at two distinct phases with respect to the neocortical slow oscillation. Specifically, SPW-Rs that occur after the peak of the neocortical UP-state were associated with higher power of the neocortical SO than SPW-Rs that precede the peak of the UP-state. In Chapter 4 I describe a novel ultra-slow (0.1-0.5 Hz) hippocampal oscillation that co-occurs with both theta and the SO and modulates faster activity during both states. This rhythm, which we call iota, has maximal power at SLM and a phase reversal 100 µm below the theta phase reversal. Inactivation of the medial septum (MS), which abolishes theta oscillations, significantly amplifies the iota rhythm during activated states. Interestingly, inactivation of the MS with lidocaine, but not muscimol, disrupted the hippocampal SO as well, and led to an iota-like but arrhythmic activity pattern that remained phase-modulated by the neocortical SO. This important finding suggests that fibers passing in the vicinity of the medial septum are critical for the expression of the hippocampal SO. During spontaneous activity, iota in the superficial layers of the entorhinal cortex was highly coherent with iota in the hippocampus, and the maximum iota-related multi-unit activity occurred in entorhinal cortex layer III, which projects directly to SLM. These results suggest that iota might be a default state of entorhinal-hippocampal networks that influences hippocampal processing during both states. Taken together, the results in this thesis show that the coordination of hippocampal circuits with the neocortex during the SO is dynamic, likely involves the integration of entorhinal and non-entorhinal inputs at SLM, and can be modified based on the strength of the neocortical SO.

• Subjects / Keywords

  • Sleep
  • Rhythms
  • Theta
  • Hippocampus
  • Slow oscillation
  • Independent component analysis

• Graduation date

  Spring 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R32N4ZR8V

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.