StateDependentProces · Markers and mechanisms of sensory disconnection
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-06-01 → 2018-05-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите на сензорното изключване при сън и анестезия се проучват чрез анализи на слухови и визуални реакции в мозъка. Това помага да се разбере как се променя възприемането на външни събития и каква е ролята на норадреналина при съзнанието.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Markers and mechanisms of sensory disconnection
With the help of the EU CIG grant, I used a combined approach of animal models and human studies to reveal the markers and mechanisms of sensory disconnection during sleep and related states. Together with my research team, we revealed that cognitive lapses after sleep deprivation in humans involve attenuated and delayed neuronal responses in the medial temporal lobe co-occurring with local sleep-like slow/theta waves (Nature Medicine 2017). In the auditory domain, we show in both rodents and humans that responses in sleep and light anesthesia are preserved up to the primary auditory cortex, but robust attenuation occurs later in high-level cortical regions. By comparing auditory responses at the level of individual neurons in animals and in neurosurgical patients across wakefulness, sleep, and anesthesia, we are revealing the stage at which sensory disconnection affects brain processing of external events. In addition, by using steady-state visual stimulation (Cerebral Cortex 2017) and hierarchical speech (Journal of Neuroscience 2017) paradigms, we show that sleep affects more strongly responses that require integration over long time intervals, and responses to high-frequency content. Finally, we tested the potential role of locus coeruleus-noradrenaline (LC-NE) system in sensory disconnection in awake humans (Current Biology 2018). Pharmacologically manipulating NE levels in double-blind placebo-controlled experiments, we found that NE modulates sensitivity and accuracy of visual perception without significant effects on decision-making. In addition, NE improved late visual responses as evident by EEG and fMRI measurements, suggesting that NE plays an enabling causal role in visual awareness by affecting late visual processing. Overall, our research is revealing how the brain responds different to the external environment in disconnected states such as sleep, anesthesia, and cognitive lapses, thereby addressing a fundamental open question in system neuroscience and sleep research, with implications for sleep disorders, consciousness research, anesthesia, and neuropsychiatric disorders. In terms of career development and reintegration, the EU CIG grant has been indispensable for my integration into an independent research position. Thanks to CIG support, I have built my own successful laboratory (http://medicine.mytau.org/nir/) . By attending international conferences, I established strong collaborations with fellow scientists who are experts in sensory physiology, sleep, functional imaging and optogenetics. I have secured tenure at Tel Aviv University and am currently in the process of being evaluated for Assistant Professor academic rank. This career progress is based on research publications, teaching, fund recruitment, and successful mentoring of graduate students - all of which have been made possible by the CIG grant.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Sleep entails sensory disconnection, a state where external stimuli fail to elicit a meaningful behavioral response and do not affect perceptual awareness. While during NREM sleep and anesthesia thalamocortical neurons are bistable and the thalamus may not relay sensory signals effectively to the cortex, disconnection persists throughout REM sleep with its wake-like activity, as well as during other physiological and pathological states. This proposal seeks to reveal the markers and mechanisms of sensory disconnection and determine to what extent sleep and cognitive factors bring about similar disconnection. I hypothesize that sensory disconnection is a result of neuromodulatory changes, leading to a functional decoupling between early sensory cortex and higher order cortices. Specifically, reduced locus coeruleus-norepinephrine (LC-NE) activity may be a key mechanism, possibly affecting high-order thalamic nuclei and preventing ascending signals from effectively driving high-order cortical neurons. The proposed research will employ a combined approach in animal models (to experimentally dissect the underlying mechanisms and obtain detailed recordings of neuronal activity) and human studies (for carefully teasing apart cognitive factors, obtaining perceptual reports, and performing whole-brain imaging). I will address the following specific aims: (Aim1) identify markers of sensory incorporation vs. disconnection during physiological sleep/wake using auditory stimulation, (Aim2) reveal the underlying mechanisms by optogenetics (rodents) and pharmacological imaging (humans), and (Aim3) compare the effects of cognitive variables on sensory processing to those of vigilance states and the experimental manipulations. Understanding sensory disconnection will help reveal how states of behavior and activity affect cortical processing in health and disease, thereby addressing a fundamental open question in sleep research and system neuroscience.
Оригинален текст от CORDIS (на английски).
Участници
- TEL AVIV UNIVERSITY · Tel AvivКоординаторИзраел
Връзки
Данни: CORDIS, © Европейски съюз
