Stimulation of the mesencephalic locomotor region (MLR) is known to initiate and maintain walking in the brainstem-transected animal by modulating locomotion oscillators present in the spinal cord. Over the past several years we have applied clsssical neurophysiological and anatomical methods in the locomotion on a treadmill preparation. Our studies have demonstrated the presence of projections from the two main outputs of the basal ganglia, the pallidum and substantia nigra (SN), to the MLR Recent findings revealed the occurrence in MLR neurons, of rhythmic firing patterns related to locomotor movements. These studies established that the pedunculopontine necleus, a known termination sitse of basal ganglia outputs, forms part of the MLR. In addition, the overall anatomical organization of other afferents and of the efferents of the MLR were described in the walking preparation. Significantly, we reported that descending MLR efferents travel via Probst's tract and to the nucleus reticularis gigantocellularis (NRG), a source of reticulospinal projections. Our latest findings provide a significant advance in the application of this preparation, not only as a model for the study of locomotion, but also as a method for investigating chemotherapeutic strategies in the treatment of diseases involving locomotor movements, e.g. Parkinsonism, stroke, trauma. The limitations of stimulation-induced locomotion (fatigability, variability and low yield) now can readily be overcome with the use of chemical-induced locomotion. We have been able to induce locomotion by application of pharmacological substances within the MLR. Our preliminary findings suggest that chemical-induced locomotion is, 1) site specific, i.e. produces locomotion only when application is made within the MLR, 2) transmitter specific, and 3) provides lasting, reproducible walking. The proposed research will take advantage of this development in order to investigate, 1) the chronology and characteristics of rhythms present in MLR, NRG and SN neurons during chemical-induced locomotion, 2) the ability of NRG to induce, or modulate MLR-induced, locomotion, and 3) the ability of the SN to modulate MLR- or NRG-induced locomotion. These studies will provide comprehensive information which should enable the design of an appropriate chemotherapeutic and/or prosthetic control for locomotor events - the ultimate aim of this research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020246-03
Application #
3400508
Study Section
Biopsychology Study Section (BPO)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
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
Garcia-Rill, E; D'Onofrio, S; Luster, B et al. (2016) The 10 Hz Frequency: A Fulcrum For Transitional Brain States. Transl Brain Rhythm 1:7-13
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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