Section I have received and accepted a position as an Assistant Professor in the Department of Neurobiology, University of Massachusetts Medical School. Therefore, I am applying for the transition to the R00 phase where I will continue to investigate parafacial zone (PZ) circuitry regulating sleep-wake cycle. The ultimate goal is to develop treatments to reduce the dysfunction and negative health effects of sleep disruption associated with multiple neurologic disorders. The subcortical structures regulating slow-wave sleep (SWS) and its electroencephalogram (EEG) correlate are incompletely understood. Continued existence of this fundamental knowledge gap represents an important problem because it reduced our ability to modulate or appropriately manipulate the brain?s sleep circuitry and hampers our ability to treat and alleviate the physiological disorders that result from sleep disruption. During the K99 phase, and as proposed in the K99 application, I have shown that selective activation of GABAergic PZ neurons promotes SWS and cortical SWA in freely behaving animals at least in part by inhibiting the parabrachial nucleus to basal forebrain to cortex ascending arousal system. The objective of the R00 phase remains identical to the K99 application and aims to finish the proposed projects by determining how other non-GABAergic PZ neurons might contribute to the regulation of SWS and cortical SWA, using a new cre-driver mouse line and similar techniques to those employed to characterize PZ GABAergic neurons.
Sleep disruption is associated with multiple neurophysiologic problems (e.g. cognition, metabolism). The long term goal of this research is to understand how the brain regulated sleep. This research will provide new insights to develop targeted pharmacological and interventional strategies to restore good quality sleep-wake function.
| Anaclet, Christelle; Griffith, Kobi; Fuller, Patrick M (2018) Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine. Neuropsychopharmacology 43:415-425 |
| Anaclet, Christelle; De Luca, Roberto; Venner, Anne et al. (2018) Genetic Activation, Inactivation, and Deletion Reveal a Limited And Nuanced Role for Somatostatin-Containing Basal Forebrain Neurons in Behavioral State Control. J Neurosci 38:5168-5181 |
| Anaclet, Christelle; Fuller, Patrick M (2017) Brainstem regulation of slow-wave-sleep. Curr Opin Neurobiol 44:139-143 |
| Anaclet, Christelle; Pedersen, Nigel P; Ferrari, Loris L et al. (2015) Basal forebrain control of wakefulness and cortical rhythms. Nat Commun 6:8744 |
| Anaclet, Christelle; Ferrari, Loris; Arrigoni, Elda et al. (2014) The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. Nat Neurosci 17:1217-24 |
