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 (2017) Mesoscale-duration activated states gate spiking in response to fast rises in membrane voltage in the awake brain, Journal of Neurophysiology 118(2):1270-1291.

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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. Non-rhythmic 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 10s-100s of ms) 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 controlling 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.

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Understanding, and simulating, the brain

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