Evidence for long-timescale patterns of synaptic inputs in CA1 of awake behaving mice

Ilya Kolb, Giovanni Talei Franzesi, Michael Wang, Suhasa B. Kodandaramaiah, Craig R. Forest, Edward S. Boyden, Annabelle C. Singer

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4 Scopus citations

Abstract

Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro. In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or “repeats.” Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10msprecision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤ 20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought.

Original languageEnglish (US)
Pages (from-to)1821-1834
Number of pages14
JournalJournal of Neuroscience
Volume38
Issue number7
DOIs
StatePublished - Feb 14 2018

Bibliographical note

Funding Information:
I.K. was funded by National Institutes of Health (NIH) Computational Neuroscience Training Grant DA-032466-02.G.T.F.wasfundedbyaFriendsoftheMcGovernInstituteFellowship.E.S.B.wasfundedbyNIHDirector’sPioneer Award1DP1-NS-087724andTransformativeAward1R01-MH-103910;aNewYorkStemCellFoundation-Robertson Award; the Cognitive Rhythms Collaborative funded by National Science Foundation Division of Mathematical Sci-

Funding Information:
encesGrant1042134;andNIHGrants1R01-EY-023173,1R01-NS-067199,and1R01-DA-029639.C.R.F.wasfunded by NIH Grants 1U01-MH-106027, 1R01-EY-023173, and 5R44-NS-08310803. A.C.S. was funded by the MIT Intelligence Initiative and the Lane Family. We thank Sunanda Sharma, Melina Tsitsiklis, Denis Bozic, and Sean Batir for training animals; and Audrey Sederberg for helpful discussions. *I.K. and G.T.F. contributed equally to this work. The authors declare no competing financial interests.

Funding Information:
I.K. was funded by National Institutes of Health (NIH) Computational Neuroscience Training Grant DA-032466-02. G.T.F. was funded by a Friends of the McGovern Institute Fellowship. E.S.B. was funded by National Institutes of Health (NIH) NIH Director’s Pioneer Award 1DP1-NS-087724 and National Institutes of Health (NIH) Transformative Award 1R01-MH-103910; aNewYork Stem Cell Foundation-Robertson Award; the Cognitive Rhythms Collaborative funded by National Science Foundation Division of Mathematical Sciences Grant 1042134; and National Institutes of Health (NIH) NIH Grants 1R01-EY-023173, National Institutes of Health (NIH) 1R01-NS-067199, and National Institutes of Health (NIH) 1R01-DA-029639. C.R.F. was funded by National Institutes of Health (NIH) NIH Grants 1U01-MH-106027, National Institutes of Health (NIH) 1R01-EY-023173, and National Institutes of Health (NIH) 5R44-NS-08310803. A.C.S. was funded by the MIT Intelligence Initiative and the Lane Family. We thank Sunanda Sharma, Melina Tsitsiklis, Denis Bozic, and Sean Batir for training animals; and Audrey Sederberg for helpful discussions.

Publisher Copyright:
© 2018 the authors.

Keywords

  • Hippocampus
  • Intracellular activity
  • Subthreshold patterns

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