A Caltech Library Service

Membrane Potential Dynamics of Hippocampal Neurons During Ripples in Awake Mice


Hulse, Bradley Kline (2017) Membrane Potential Dynamics of Hippocampal Neurons During Ripples in Awake Mice. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z95Q4T3S.


During periods of slow wave sleep and quiet wakefulness, the hippocampal formation generates spontaneous population bursts that are organized as a high-frequency "ripple" oscillation. The neurons that participate in these bursts often replay previously experienced activity patterns encoded during alert behavior, and interfering with ripple generation produces deficits in learning and memory tasks. For these reasons, ripples play a prominent role in theories of memory consolidation and retrieval. While spiking during ripples has been extensively studied, our understanding of the subthreshold behavior of hippocampal neurons during these events remains incomplete. Here, we combine in vivo whole-cell recordings with multisite extracellular and behavioral measurements to study the membrane potential dynamics of hippocampal neurons during ripples in awake mice. We find that the subthreshold depolarization of CA1 pyramidal neurons is uncorrelated with net excitatory input, clarifying the circuit mechanism keeping most neurons silent during ripples. On a finer time scale, the phase delay between intracellular and extracellular ripple oscillations varies systematically with the membrane potential, which is inconsistent with models of intracellular ripple generation involving perisomatic inhibition alone. In addition, we find that membrane potential statistics (mean, variability, distance to threshold) of CA1 pyramidal neurons and dentate granule cells are systematically modulated across brain states, that rapid variations in pupil diameter are reflected in subthreshold fluctuations, and that many neurons begin depolarizing about one second before ripple onset. These results provide evidence that coordinated shifts in the subthreshold dynamics of individual neurons may contribute to the emergence of state-dependent hippocampal activity patterns. Finally, we present evidence that area CA3 provides the major excitatory input to dentate granule cells during ripples and that there are coordinated interactions between hippocampal ripples and population events in the dentate gyrus, both of which inform network-level models of ripple generation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Brain State, Hippocampus, Ripples, Sharp Waves, Large Irregular Activity, Small Irregular Activity, Theta, Neuromodulation, Arousal, Membrane Potential, Intracellular, Whole-Cell, Local Field Potential, Excitation, Inhibition
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Neurobiology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Siapas, Athanassios G.
Thesis Committee:
  • Dickinson, Michael H. (chair)
  • Prober, David A.
  • Sternberg, Paul W.
  • Siapas, Athanassios G.
Defense Date:14 November 2016
Non-Caltech Author Email:bradkhulse (AT)
Record Number:CaltechTHESIS:01052017-162955208
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for chapter 2.
Hulse, Bradley Kline0000-0002-7117-7036
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10004
Deposited By: Bradley Hulse
Deposited On:09 Mar 2017 22:41
Last Modified:31 Oct 2019 21:33

Thesis Files

PDF - Final Version
See Usage Policy.


Repository Staff Only: item control page