Weakly Correlated Local Cortical State Switches under Anesthesia Lead to Strongly Correlated Global States

• Published in: The Journal of neuroscience 2022-11, Vol.42 (48), p.8980-8996
• Main Authors: Blackwood, Ethan B, Shortal, Brenna P, Proekt, Alex
• Format: Article
• Language: English
• Subjects: Activity patterns; Anesthesia; Animals; Brain; Coupling; Heterogeneity; Isoflurane; Isoflurane - pharmacology; Male; Metastable state; Neurons - physiology; Rats; Sensorimotor integration; Sleep and wakefulness; Statistical analysis; Switches; Thalamus; Wakefulness; Wakefulness - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.0123-22.2022

During recovery from anesthesia, brain activity switches abruptly between a small set of discrete states. Surprisingly, this switching also occurs under constant doses of anesthesia, even in the absence of stimuli. These metastable states and the transitions between them are thought to form a "scaffold" that ultimately guides the brain back to wakefulness. The processes that constrain cortical activity patterns to these states and govern how states are coordinated between different cortical regions are unknown. If state transitions were driven by subcortical modulation, different cortical sites should exhibit near-synchronous state transitions. Conversely, spatiotemporal heterogeneity would suggest that state transitions are coordinated through corticocortical interactions. To differentiate between these hypotheses, we quantified synchrony of brain states in male rats exposed to a fixed isoflurane concentration. States were defined from spectra of local field potentials recorded across layers of visual and motor cortices. A transition synchrony measure shows that most state transitions are highly localized. Furthermore, while most pairs of cortical sites exhibit statistically significant coupling of both states and state transition times, coupling strength is typically weak. States and state transitions in the thalamic input layer (L4) are particularly decoupled from those in supragranular and infragranular layers. This suggests that state transitions are not imposed on the cortex by broadly projecting modulatory systems. Although each pairwise interaction is typically weak, we show that the multitude of such weak interactions is sufficient to confine global activity to a small number of discrete states. The brain consistently recovers to wakefulness after anesthesia, but this process is poorly understood. Previous work revealed that, during recovery from anesthesia, corticothalamic activity falls into one of several discrete patterns. The neuronal mechanisms constraining the cortex to just a few discrete states remain unknown. Global states could be coordinated by fluctuations in subcortical nuclei that project broadly to the cortex. Alternatively, these states may emerge from interactions within the cortex itself. Here, we provide evidence for the latter possibility by demonstrating that most pairs of cortical sites exhibit weak coupling. We thereby lay groundwork for future investigations of the specific cellular and network mechanisms of corticocortica