Perceptions, thoughts, actions, and cognition in general are brought about by ensembles of neurons engaging in dynamic, coordinated activity. Neurons are morphologically and functionally specialized and can change their momentary pattern of activity during the course of perceptual or cognitive functioning. We wish to better understand how communication occurs among different groups of neurons and how its dynamics is affected by anesthetics when the subject’s state of consciousness is altered. Specifically, we ask how is the probability of message passing between specific neurons that form a functional circuit is altered by the state? Several approaches have been taken to answer these questions.
In one of our projects we quantify the dose-dependent effect of anesthetics on monosynaptic functional connectivity of individual neurons in the cerebral cortex. To-date we have found that the inhalational anesthetic desflurane decreases the strength of monosynaptic spike transmission through excitatory synapses while the strength of inhibitory synaptic transmission is overall unchanged. This is surprising, since many patch clamp studies of synaptic function in vitro found that the dominant effect of anesthetics was an enhancement of inhibitory signaling. Our finding emphasizes the importance of investigations in intact neuronal circuits in which the complex wiring connections are preserved. Ongoing studies aim to investigate if the same result would apply to other types of anesthetics and perhaps, other forms of unconsciousness.
Vizuete JA, Pillay S, Diba K, Ropella KM, Hudetz AG. Monosynaptic functional connectivity in cerebral cortex during wakefulness and under graded levels of anesthesia. Front Integr Neurosci. 2012;6:90. PubMed PMID: 23091451; PMCID: 3469825.
When anesthetics are applied at an increasing dose, the temporal pattern of neuronal activity is gradually changed from virtually continuous form to frequently interrupted, fragmented form. In anesthesia, neurons emit short bursts of spikes, sometimes called UP states, which alternate with less active periods or DOWN states. The UP states of individual neurons also get disorganized suggesting that neurons are disconnected. This derangement of temporal organization of neuronal spiking activity may be an important underlying mechanism affecting failure conscious sensory integration under anesthesia.
Hudetz AG, Vizuete JA, Imas OA. Desflurane selectively suppresses long-latency cortical neuronal response to flash in the rat. Anesthesiology 2009, Aug, 111(2):231-9. PMCID: 2761678
Vizuete JA, Pillay S, Ropella KM, Hudetz AG. Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats. Neuroscience. 2014;275:340-51. PubMed PMID: 24952333; PMCID: 4165556.
At the end, it all comes down to the brain’s ability to process, store, and retrieve information. All conscious and subconscious activities from relatively simple sensory-motor responses to abstract thinking depend on processing information of some sort. A sufficiently large capacity of the brain to hold and manipulate information is thought to be a prerequisite for consciousness.
Hudetz AG, Vizuete JA, Pillay S, Ropella KM. Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats. Anesthesiology. 2015. Epub 2015/05/09. PubMed PMID: 25955982.*
*This work received Best Abstract presentation at the 2014 Annual Meeting of the American Society of Anesthesiologists.
From correlation to causation.
Is the uncoupling of neurons really responsible for loss of consciousness? One way to investigate this is to attempt to restore neuronal connectivity or information exchange and see if the subjects wake up despite still being under the influence of the anesthetic. (This is sometimes called the “reanimation” experiment.) It turns out that electrical stimulation of the brainstem nucleus Pontis Oralis – a site that plays a central role in maintaining the overall level of neuronal activity, significantly increases the information associated with neuronal interactions in the cortex, especially in the posterior association areas that are responsible for multimodal integration. Brainstem stimulation also augments neuronal interactions induced by sensory stimulation of the retina with light flashes. However, the animals do not show any sign of waking up!
This unexpected result suggests that waking behavior requires more than information gain in the posterior cortex. Of course we don’t know if they regain any conscious experience. More research is necessary to identify the neural circuit interactions that are necessary for regaining consciousness.
Pillay S, Vizuete J, Liu X, Juhasz G, Hudetz AG. Brainstem stimulation augments information integration in the cerebral cortex of desflurane-anesthetized rats. Front Integr Neurosci. 2014 Feb 24;8:8. PubMed PMID: 24605091; PubMed Central PMCID: PMC3932553.