Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2018-2019)

Background : I am interested in the understanding of physiological basis of conscious states, which is essentially a cortical phenomenon. Almost all information reaching cerebral cortex passes through the thalamus, which is a key element in the understanding of cortical function. Morphology and physiology of sensory thalamus and thalamocortical system (somatosensory, visual etc) is known. However, the role of midline thalamic nuclei (MTN) remains largely obscure. Neurons from these nuclei are likely responsible for the generation of conscious vs. unconscious states and different levels of alertness. I propose to investigate not only how these neurons are implicated in the generation of brain states, but also how a modification of their excitability could affect behavioral performance.
Objectives : (1) To evaluate the main sources of inhibition in MTN, (2) to evaluate patterns of activity of MTN during brain activated states (wake, REM sleep) vs. slow-wave sleep, (3) to manipulate MTN excitability and to affect the expression of sleep-wake states and behavioral performance.
Hypothesis : Thalamocortical neurons from MTN provide control of cortical excitability and mediate generation of states, like sleep and wake. They control levels of alertness.
Methods: (1) Retrograde labeling to determine the main inputs to MTN, combined with optogenetic stimulation and electrophysiological recordings. (2) Intracellular recordings in vivo from MTN neurons during brain oscillatory states (mainly anesthesia). (3) Neuronal firing recording from MTN neurons during different states of vigilance. (4) Pharmacogenetic modulation of MTN excitability and its effects on sleep-wake cycle as well as behavioral performance.
Originality and feasibility: Very few studies investigated MTN; no intracellular recordings from these cells are available in the literature. Therefore, everything proposed above will be new. Intracellular recording technique is very complex and difficult to do on mice. Dr. Timofeev lab pioneered intracellular recordings in non-anesthetized animals, it also recently published a number of papers where intracellular recordings were done on mice, therefore the technically complex experiments appear feasible.
Contribution to the advancement of knowledge:
Systematic knowledge on the role of MTN neurons in brain functions does not exist. We propose series of experiments to investigate what role these nuclei play in the generation of states of vigilance and overall alertness.