Disruption of cortical network activity by the general anaesthetic isoflurane

Abstract

Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.

Evidence that PV+ cells enhance temporal population codes but not stimulus-related timing in auditory cortex

“…Burst duration varied with stimulus intensity and across slices, but was typically around 40-70ms ( Figure 1D). Network bursts of similar duration have been observed previously in vitro (Hentschke et al 2017;Krause et al 2014;MacLean et al 2005;Metherate and Cruikshank 1999;Shu et al 2003) and in auditory cortex in response to acoustic stimuli in vivo (Curto et al 2009;Luczak et al 2009;2013;Sakata and Harris 2009).…”

“…Duration of bursts can also be affected by the method for detecting and defining bursts, which differs across studies. For example, the duration of the thresholded MUA signal in layer 5 was typically less than the intracellular depolarization signal ( Figure 1B), though we note that the vast majority of spiking activity occurred within the detected bursts according to our definition (Hentschke et al 2017;Krause et al 2014).…”

“…The absence of precise timing in pyramidal cells relative to the stimulus train was unexpected given the importance of, and specialization for, timing information in the ascending auditory pathway (Elhilali et al 2004;Heil and Irvine 1997;Phillips and Hall 1990;Rose and Metherate 2005), but may reflect a transition from timing/feature-based coding to rate/object-based coding in auditory cortex (Wang et al 2008). Indeed, we have shown that monosynaptically driven spikes in pyramidal cells are rare in auditory cortex, with most spiking occurring in the context of network bursts induced by thalamic stimulation (Hentschke et al 2017;Krause et al 2014). On the background of this ongoing activity, thalamic synaptic responses are less effective at driving precise spiking responses, and spike timing may be influenced significantly by intrinsic cortical activity.…”

“…Sensory stimulation triggers synaptic and spiking activity that occurs on the background of spontaneous network activity. The largest responses occur when activation of thalamic or cortical afferents triggers correlated network activity within the cortical column (Hentschke et al 2017;Krause et al 2014;Luczak et al 2013;Sakata and Harris 2009). The spatio-temporal patterns of spiking activity (packets) during these network bursts in auditory cortex are preserved across the synchronized-desynchronized state continuum, suggesting that the fundamental structure of network activity can be elucidated by examining network bursts in isolation.…”

Optogenetic activation of afferent pathways in brain slices and modulation of responses by volatile anesthetics

“…The elusiveness of the mechanisms underlying loss and return of consciousness during anesthesia may be attributed partially to non-linear, synergistic actions of anesthetics at the cellular, network, and systems levels 15 . Isoflurane, for example, suppresses activity within select brain regions 16-18 , impairs connectivity between distant brain regions 19-23 , and diminishes synaptic responses in a pathway-specific manner 24,25 . Which effects of anesthetics, from the molecular to the systems level, are necessary or sufficient to effect loss of consciousness remains unclear.…”