Cholinergic mesopontine cell groups, in concert with catecholaminergic (and serotonergic) neurons, participate in the descending control of locomotion and of postural muscle tone (e.g., startle response and atonia of REM sleep). As part of the Reticular Activating System (RAS), ascending projections of these cells modulate changes in state (e.g., sleep-wake cycles) and the response to afferent input (e.g., sensory gating). That is, they are in a crucial position to modulate fight vs flight responses. The applicants' work has implicated these neurons in psychiatric (e.g., schizophrenia, anxiety disorder), neurological (e.g., Parkinson's Disease) and sleep (e.g., narcolepsy, REM behavior disorder) disturbances, all of which have sleep-wake cycle and motor dysregulation in common. Studies during the previous grant period identified the presence of a novel mechanism whereby mesopontine cholinergic neurons may induce changes in state in descending target neurons. The proposed studies will investigate the characteristics and pharmacological control of this mechanism with a view towards determining the manner in which postural and locomotion systems are switched on and off. In addition, the applicants have developed a preparation in the behaving animal allowing the non-invasive recording of a waveform which is a measure of the ascending output of the RAS. Preliminary data suggest that localized injections of neuroactive agents into the mesopontine region can modulate this vertex-recorded waveform. The proposed studies will investigate the characteristics and pharmacological control of this waveform with a view towards determining the manner in which arousal and sensory gating systems are controlled. This work is of critical importance in the understanding of, and design of therapeutic strategies for, a number of psychiatric, neurological and sleep-wake cycle disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS020246-15S1
Application #
6323578
Study Section
Biopsychology Study Section (BPO)
Program Officer
Heetderks, William J
Project Start
1984-03-01
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
15
Fiscal Year
2000
Total Cost
$40,000
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
González, Betina; González, Candela; Bisagno, Verónica et al. (2017) EFFECTS OF METHAMPHETAMINE ON LOCOMOTOR ACTIVITY AND THALAMIC GENE EXPRESSION IN LEPTIN-DEFICIENT OBESE MICE. Transl Brain Rhythm 2:
Rozas, José L; Goitia, Belén; Bisagno, Verónica et al. (2017) Differential alterations of intracellular [Ca2+] dynamics induced by cocaine and methylphenidate in thalamocortical ventrobasal neurons. Transl Brain Rhythm 2:
Urbano, Francisco J; Bisagno, Verónica; Garcia-Rill, Edgar (2017) Arousal and drug abuse. Behav Brain Res 333:276-281
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Luster, Brennon R; Urbano, Francisco J; Garcia-Rill, Edgar (2016) Intracellular mechanisms modulating gamma band activity in the pedunculopontine nucleus (PPN). Physiol Rep 4:
D'Onofrio, Stasia; Urbano, Francisco J; Messias, Erick et al. (2016) Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons. Physiol Rep 4:
Goitia, Belén; Rivero-Echeto, María Celeste; Weisstaub, Noelia V et al. (2016) Modulation of GABA release from the thalamic reticular nucleus by cocaine and caffeine: role of serotonin receptors. J Neurochem 136:526-35
Garcia-Rill, Edgar; D'Onofrio, Stasia; Mahaffey, Susan et al. (2015) Pedunculopontine arousal system physiology-Implications for schizophrenia. Sleep Sci 8:82-91
D'Onofrio, Stasia; Kezunovic, Nebojsa; Hyde, James R et al. (2015) Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder. J Neurophysiol 113:709-19
Garcia-Rill, Edgar; Luster, Brennon; D'Onofrio, Stasia et al. (2015) Pedunculopontine arousal system physiology - Deep brain stimulation (DBS). Sleep Sci 8:153-61

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