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

Abstract

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. 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.

Volumetric mapping of the functional neuroanatomy of the respiratory network in the perfused brainstem preparation of rats

“…Such a mechanism has been observed, for instance, in simultaneous recordings of LFPs and intracellular neuronal activity in visual cortex (Singer et al . 2017). This latter mechanism may be particularly relevant for the rLFPs observed in the DRG at the PI–E2 transition (see below).…”

“…Such a purely synaptic mechanism for the generation of LFPs has been observed, for instance, in hippocampal CA1 neurons (Singer et al . 2017). In this case, synaptic inputs from other brainstem respiratory areas impinging upon DRG neurons precisely at the PI–E2 transition (and more variably during the post‐inspiratory period) may function to transiently bring DRG sensory relay populations closer to their firing threshold and thereby transiently increase the sensitivity of the respiratory network to sensory and behavioural inputs targeting the DRG.…”

Population imaging of neural activity in awake behaving mice in multiple brain regions

“…The hippocampus has typically been regarded as having little topographical organization 43,44 , although some evidence has suggested that a degree of spatial clustering exists 45,46 . Recently, based upon multi-neuron automated patch clamp data 47 , we hypothesized that even when nearby neurons in the awake mouse hippocampus exhibit highly coordinated subthreshold activities, they might be capable of generating extremely divergent spiking outputs. Since we were unable to analyze more than one cell in the hippocampus at a time, however, even with automated patch clamp, we were previously unable to test this hypothesis.…”

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

“…One of the solutions can be the automation of the process [ 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]. Several groups have developed patch-clamping robots and succeeded in obtaining in vivo whole-cell recordings from the neocortex and the hippocampus [ 203 , 206 , 211 ], even from deeper areas (e.g., the thalamus) [ 212 ]. Recently, Annecchino et al and Suk et al established automation of in vivo targeted patch-clamp recording [ 204 , 208 ].…”