Basal Forebrain-Hypothalamic Networks Supporting Wakefulness

Elda Arrigoni
Beth Israel Deaconess Medical Center
Friday, February 28, 2020 - 11:00am
Ramsay Wright Building, Room 432
Departmental Seminar
Sleep and wake cycles are integral and necessary parts of our life. The neuronal circuits regulating sleep and wakefulness are just becoming delineated. Of the different structures involved in sleep and wake regulation, the basal forebrain (BF) is a key component and its structural and functional integrity is an absolute requirement for maintaining behavioral and electroencephalographic (EEG) wake. The mechanisms and substrates by which the BF regulates EEG and neurobehavioral arousal remains however poorly understood. A review of the relevant literature reveals that the vast majority of studies on BF circuitry have focused on the cholinergic BF system in physiological (EEG and behavioral arousal) and pathophysiological (neurodegenerative disorders) regulation, despite the fact that 1) lesions of the cholinergic BF system produce limited changes in EEG or behavioral wake; and 2) the BF also contains GABAergic and glutamatergic neurons that roughly intermingle with the cholinergic neurons. Recent studies have shown that chemogenetic activation of the BF GABAergic population increases the amount of time that mice are awake and optogenetic stimulations of these neurons rapidly wake mice up from sleep. Thus, while it is now accepted that other BF neurotransmitter systems may interact or work in parallel with cholinergic neurons in the control of sleep and wake, the contribution of GABAergic BF neurons, and in particular their network output, to these processes remains largely unexplored. Our hypothesis is that BF GABAergic descending projections are critically involved in maintaining behavioral wake. The focus of this presentation is on the role of BF GABAergic neurons and, in particular, the circuit basis through which BF promotes behavioral arousal.
John Peever
Dept of Cell and Systems Biology