The long term goal of the research is to elucidate the neural and chemical mechanisms generating sleep- wake states and regulating cortical activity and behavior across those states. Such understanding will illuminate how neurological diseases, such as Alzheimer's, or sleep-wake disorders, such as narcolepsy, result in loss of attention and/or the ability to maintain an aroused, waking state. The proposed studies focus upon the role of cholinergic, GABAergic and newly discovered glutamatergic neurons in the basal forebrain (BF). Using juxtacellular labeling of neurons recorded in unanesthetized, head-fixed rats, the discharge of immunohistochemically identified cells will be characterized in association with electroencephalographic (EEG) activity recorded from the cortex and electromyographic (EMG) activity recorded from postural neck muscles across the states of waking, slow wave sleep (SWS) and paradoxical sleep (PS, also known as rapid eye movement sleep, REMS, in humans). Applying newly developed behavioral testing, previously identified W/PS-active, cholinergic BF neurons will be examined for their discharge in association with attention and cortical activation during waking. GABAergic BF neurons will be further studied for their discharge in association with sleep, as SWS or SWS/PS-active cells, and in reciprocal relation to the cholinergic cells in attentional tasks. The unique role of glutamatergic BF neurons will be characterized in relation to cortical activity, behavioral arousal and attention or reinforcement. By neuroanatomical tracing combined with immunohistochemistry for presynaptic vesicular transporter proteins and postsynaptic proteins, projections and synaptic connections of BF cholinergic, GABAergic and glutamatergic neurons will be delineated onto target neurons in the cerebral cortex. Collectively, these studies will elucidate how specific basal forebrain cell groups can promote attention along with cortical activation or behavioral arousal and others reciprocally dampen these processes to evoke drowsiness and sleep. They will provide insight into how imbalances in these systems could lead to deficits in attention and arousal as well as disruption of sleep-wake states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060119-11
Application #
8101292
Study Section
Biological Rhythms and Sleep Study Section (BRS)
Program Officer
Vicentic, Aleksandra
Project Start
2000-07-06
Project End
2013-03-30
Budget Start
2011-07-01
Budget End
2013-03-30
Support Year
11
Fiscal Year
2011
Total Cost
$173,099
Indirect Cost
Name
Mcgill University
Department
Type
DUNS #
205667090
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 0-G4
Jones, Barbara E (2017) Principal cell types of sleep-wake regulatory circuits. Curr Opin Neurobiol 44:101-109
Hassani, Oum Kaltoum; Krause, Matthew R; Mainville, Lynda et al. (2016) Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes. J Neurosci 36:1747-57
Boucetta, Soufiane; Cissé, Youssouf; Mainville, Lynda et al. (2014) Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci 34:4708-27
Jones, Barbara E (2011) Neurobiology of waking and sleeping. Handb Clin Neurol 98:131-49
Hassani, Oum Kaltoum; Henny, Pablo; Lee, Maan Gee et al. (2010) GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep. Eur J Neurosci 32:448-57
Henny, P; Brischoux, F; Mainville, L et al. (2010) Immunohistochemical evidence for synaptic release of glutamate from orexin terminals in the locus coeruleus. Neuroscience 169:1150-7
Hassani, Oum Kaltoum; Lee, Maan Gee; Jones, Barbara E (2009) Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci U S A 106:2418-22
Hassani, Oum Kaltoum; Lee, Maan Gee; Henny, Pablo et al. (2009) Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep-wake cycle. J Neurosci 29:11828-40
Henny, Pablo; Jones, Barbara E (2008) Projections from basal forebrain to prefrontal cortex comprise cholinergic, GABAergic and glutamatergic inputs to pyramidal cells or interneurons. Eur J Neurosci 27:654-70
Modirrousta, Mandana; Mainville, Lynda; Jones, Barbara E (2007) Dynamic changes in GABAA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery. BMC Neurosci 8:15

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