Mesoscale-duration activated states gate spiking in response to fast rises in membrane voltage in the awake brain

Annabelle C. Singer, Giovanni Talei Franzesi, Suhasa B. Kodandaramaiah, Francisco J. Flores, Jeremy D. Cohen, Albert K. Lee, Christoph Borgers, Craig R. Forest, Nancy J. Kopell, Edward S. Boyden

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Seconds-scale network states, affecting many neurons within a network, modulate neural activity by complementing fast integration of neuron-specific inputs that arrive in the milliseconds before spiking. Nonrhythmic subthreshold dynamics at intermediate timescales, however, are less well characterized. We found, using automated whole cell patch clamping in vivo, that spikes recorded in CA1 and barrel cortex in awake mice are often preceded not only by monotonic voltage rises lasting milliseconds but also by more gradual (lasting tens to hundreds of milliseconds) depolarizations. The latter exert a gating function on spiking, in a fashion that depends on the gradual rise duration: the probability of spiking was higher for longer gradual rises, even when controlled for the amplitude of the gradual rises. Barrel cortex double-autopatch recordings show that gradual rises are shared across some, but not all, neurons. The gradual rises may represent a new kind of state, intermediate both in timescale and in proportion of neurons participating, which gates a neuron’s ability to respond to subsequent inputs. NEW & NOTEWORTHY We analyzed subthreshold activity preceding spikes in hippocampus and barrel cortex of awake mice. Aperiodic voltage ramps extending over tens to hundreds of milliseconds consistently precede and facilitate spikes, in a manner dependent on both their amplitude and their duration. These voltage ramps represent a “mesoscale” activated state that gates spike production in vivo.

Original languageEnglish (US)
Pages (from-to)1270-1291
Number of pages22
JournalJournal of neurophysiology
Issue number2
StatePublished - Aug 14 2017

Bibliographical note

Funding Information:
A. C. Singer was funded by the MIT Intelligence Initiative. G. Talei Franzesi was funded by a Friends of the McGovern Institute Fellowship. E. S. Boyden was funded by NIH Director’s Pioneer Award 1DP1NS087724 and Transformative Award 1R01MH103910-01, a New York Stem Cell Foundation-Robertson Award, the Cognitive Rhythms Collaborative funded by NSF DMS 1042134, and NIH Grants 1R01EY023173, 1R01NS067199, and 1R01DA029639. C. Borgers and N. J. Kopell were funded by NIH Grant 1R01 NS067199. S. B. Kodandaramaiah received financial remuneration from Neuromatic Devices for technical consulting services.

Publisher Copyright:
© 2017 the American Physiological Society.


  • Action potential
  • Barrel cortex
  • CA1
  • Hippocampus
  • Intracellular recording
  • Network state
  • Subthreshold dynamics


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