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

December 26, 2017 by Matthew Attokaren

Figure 4.

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 100-300 ms periods re-occurs 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 8/9 recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or “repeats”. Repeats generally were high-amplitude, non-oscillatory events reoccurring with 10 millisecond precision. 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 or less, 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 non-stochastically, 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.

SIGNIFICANCE STATEMENT

We found long (900 ms or more) repeated subthreshold patterns of activity in CA1 of awake, behaving mice. These repeated patterns (‘repeats’) occurred more often than expected by chance and with 10 millisecond precision. Most spikes occurred within repeats and reoccurred with a precision on the order of 20 ms. Surprisingly, there was no correlation between repeat occurrence and classical network states such as theta oscillations and sharp-wave ripples. These results provide strong evidence that long patterns of activity are repeated and transmitted to downstream neurons, suggesting that the hippocampus can generate longer sequences of repeated activity than previously thought.

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NEWS

Congratulations to Nuri Jeong for winning a Young Investigator Training Program award for the 10th IBRO World Congress of Neuroscience in Daegu, Korea this year.  Great job, Nuri!  

Annabelle Singer and Dean McLaughlin discuss memory, Alzheimer’s, and our research in the Dean’s podcast, The Uncommon Engineer:           Listen to more episodes of the Dean’s Uncommon Engineer series here:

As a National Academy of Sciences Kavli Fellow, Dr. Singer attended the 18th Chinese-American Kavli Frontiers of Science symposium in Nanjing, China. The Kavli Frontiers of Science symposium series (KFoS) is the Academy’s premiere activity for distinguished young scientists.  Kavli Frontiers of Science symposia bring together outstanding young scientists to discuss exciting advances and opportunities in a […]

Congratulations to Steph Prince for being selected for the SFN Trainee Professional Development Award.  More details here.  

The Singer lab was awarded a 5-year grant from the NIH National Institute for Neurological Disorders and Stroke (NINDS).  We are grateful to the NIH for it’s continued support of basic research.

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